A Heart-Wrenching Meeting

Last month I was given a wonderful opportunity, receiving a Patient Advocate Scholarship from the Conquer Cancer Foundation to attend this year’s 50th American Society of Clinical Oncology (ASCO) Annual Meeting.  As an independent advocate, I’m usually in the position of needing to cover my own expenses.  The result is that there are far too many important meetings I’d like to attend every year that I simply cannot, so I often have difficult choices to make.  It was for that reason that I hadn’t been able to attend ASCO’s Annual Meeting for a few years—so I was delighted to be on my way to Chicago to attend the sessions in person again, rather than following the news remotely.

ASCO 2014 Annual Meeting

ASCO 2014 Annual Meeting

The ASCO Annual Meeting is always a valuable conference and, for the oncologists who attend, it can be practice-changing.  When I first attended the ASCO Annual Meeting as a new advocate, it left a tremendous impression on me.  The sheer numbers of people streaming through the immense McCormick Conference Center, the different languages I heard all around me, the dozens of sessions occurring simultaneously, the camera crews interviewing oncologists about breaking news, and being right there in the audience, often with thousands of others, hearing long-awaited findings from critical clinical trials—all around, it was an invaluable experience for me as a survivor as well as a committed cancer research advocate.  But by far my most lasting impression resulted from my discussions with several fellow advocates who were also attending ASCO—some for the first time like myself and others who had been present every year for decades.  I had attended several breast-cancer-specific conferences by that time and had made many lasting friendships with breast cancer advocates.  But the ASCO meeting was the first time that I’d met a large number of advocates whose efforts focused on so many different types of cancer—pancreatic, lung, ovarian, and esophageal cancers, lymphomas, leukemias, and others.  And I found that of course, there were important differences in focus depending on the form of cancer: for example, the very real concerns about stigma impacting lung cancer patients, due to an unspoken feeling by some that they have somehow “caused themselves to have cancer by smoking”; the fact that there are smaller numbers of advocates and resources for pancreatic cancer, lung cancer, and other cancer types due to the unfortunate reality of poor survival rates and numbers of patients; and this names just a few.  BUT I was immediately struck by how much we all shared, having similar concerns, challenges, passions, and frustrations—and by how much we all could learn from and teach one another.  Thanks to that first ASCO meeting, I made friendships with many advocates that will last a lifetime, and we have all reached out to one another over the years since for advice, to share resources, to offer advocacy opportunities, to connect newly diagnosed patients with important support, and to collaborate on critical advocacy efforts.

And all that I just described held true for me during this year’s meeting: how gratifying it was to be surrounded by so many who are dedicating their lives to treating, preventing, and curing cancer; to see dear advocate friends again and to meet talented new advocates who are performing such crucial work; and to participate in and witness new collaborations and partnerships being formed between advocates, researchers, clinicians, and all stakeholders in the cancer landscape.

But …

Something happened during this year’s ASCO meeting that was quite literally heart-wrenching.  And it painfully brought into focus my changing perspective as a now older, perhaps more “hardened” advocate.

The moment occurred when I was sitting in the audience with hundreds of other people during a session entitled, “50 Years of Advances in Breast Cancer Treatment: What Have We Learned? Where Are We Going?”  And the fact is that in the last decade alone, we have made critical advances and learned so much about the biology of breast cancer, which in turn ultimately led to crucial new treatment approaches–perhaps most notably, trastuzumab (Herceptin®) for the targeted treatment of HER2+ breast cancers.  But as I listened to the speakers,  I found myself reflecting on how much we still do not know.  Are we just now only learning the right questions to ask?  What about the terrible reality of resistance that often develops to new agents, including targeted therapies–and of tumor dormancy for ER+ breast cancers that, in about one-third of patients, ultimately leads to a diagnosis of metastatic breast cancer often decades after a patient’s original diagnosis?  And what about what many call the incrementalism that impacts cancer research, where the investment of many years and millions of dollars, as well as the involvement of tens of thousands of cancer patients in clinical trials, may lead to a drug approval based on just weeks’ improvement in overall survival or on surrogate endpoints?  Most importantly, what about the fact that we do not yet have a cure for metastatic breast cancer?

Celebrating my 4th birthday with my first cousin (the cutie with the blond hair) and friends

Celebrating my 4th birthday with my first cousin (the cutie with the blond hair) and friends

To break my chain of thought, I glanced down at my cell phone, planning to quickly check my messages and then turn my full attention back to the speakers.  And that is the moment when I saw the message that broke my heart and turned everything around me grey.  My first cousin, my best friend when we were little, the one I worshipped, had just been diagnosed with metastatic HER2+ breast cancer.  As I sat in that conference room, and the speakers continued to talk about the crucial advancements made for breast cancer patients in the last 50 years, and the audience members all around me were taking notes, snapping pictures of the slides, talking about the presentation, or simply listening, I was angrily wiping tears from my face, thinking over and over to myself, “It’s not enough!  It’s nowhere near enough!  My cousin, my friends with mets, everyone with BC mets, they need a cure, and they need it NOW!”

These thoughts stayed with me during the remainder of the meeting, including when I was listening to what was perhaps the most reported session in the media—a session that made everything even greyer.  It was during this session that Dr. Martine Piccart-Gebhard reported the long-awaited results of a large, multicenter phase III study called the ALTTO trial, which randomized over 8,000 women with HER2+ breast cancer following surgery to either concurrent trastuzumab and lapatinib (Tykerb®), trastuzumab followed by lapatinib, or trastuzumab alone for one year.  The patients in the trial received anti-HER2 therapy either after completing all chemotherapy, concurrently with a non-anthracycline, platinum-based regimen, or concurrently with anthracycline followed by a taxane.  (A fourth arm of the trial, where lapatinib alone was compared to trastuzumab, was closed due to futility in 2011.)

Dr. Martine Piccart-Gebhart

Dr. Martine Piccart-Gebhart presenting the first ALTTO Trial Results

When Dr. Piccart-Gebhard presented these first results of the ALTTO trial during this meeting, she announced that the results disproved the hypothesis that dual anti-HER2 therapy with trastuzumab and lapatinib in the adjuvant (postsurgical) setting enhances clinical outcomes in patients with early-stage HER2+ breast cancer.  She reported that at four years, disease-free survival, the primary outcome of the trial, was 86% with trastuzumab alone, compared with 87% with trastuzumab followed by lapatinib (*P=.610, hazard ratio, 0.96) and with 88% with concurrent trastuzumab and lapatinib (P = .048; hazard ratio, 0.84).

Median overall survival rates were 94% with trastuzumab alone and 95% with both combination treatment arms.   Dr. Piccart-Gebhart also reported that lapatinib was associated with significant increases in diarrhea, skin rash, and liver events, stressing that this may explain why just 60% to 78% of patients in the lapatinib-receiving arms of the trial received at least 85% of the protocol’s specified dose.

In other words, the primary endpoint of disease-free survival was not statistically significant—i.e., no better with the combination of these two specific HER2-targeted agents when compared to trastuzumab alone—and furthermore, lapatinib was associated with more side effects. These results were a serious disappointment, and the expert commentary grimly emphasized the significance of the information gained from this trial.

*What is a P value and hazard ratio?

In most studies, a P value of less than .05 is selected to determine statistical significance, meaning that if the data show that the “null hypothesis” has less than a 5% chance of being correct, then it is wrong.  The null hypothesis is the hypothesis that an observed difference is due to chance alone and implies no effect or relationship between phenomena.  A hazard ratio is the measure of how frequently a specific event occurs in one group compared to how often it occurs in another group over time.  In cancer clinical trials, hazard ratios are frequently used to measure survival at a particular point of time in patients who have received a specific treatment compared to a control group who received another treatment or placebo.  A hazard ratio that equals 1 indicates that there is no difference in survival between the treatment and control groups, with a ratio of more or less than 1 meaning that survival was better in one of the groups.  Together, the P value is used to reject the null hypothesis that the hazard ratio equals 1—that is, that the treatment being studied is not beneficial.

Invited discussant Dr. George Sledge, Jr., former president of ASCO and chief of oncology and professor of medicine at Stanford University Medical Center, reminded the audience of the thrilling moment during the 2005 ASCO Annual Meeting, when the first results were announced for adjuvant treatment of early-stage HER2+ breast cancer with trastuzumab, the first anti-HER2 targeted therapy.  He described this as a “defining moment in our field,” where the associated 50% reduction in the annual risk of recurrence still “remains one of the great success stories.”  But “there was still real work to be done,” and he emphasized that such efforts involved evaluating biology-based approaches, explaining that the combination of trastuzumab with kinase inhibition “at the time appeared to be the best bet.”  (Kinases are enzymes that activate proteins by “signal transduction cascades,” when a molecule outside a cell activates a specific receptor either inside the cell or on its surface.  Activation of the receptor then triggers a cascade of events inside the cell, which may alter gene expression, the cell’s metabolism, or its ability to divide, for example.)  Lapatinib is an anti-HER2 agent that inhibits the intracellular tyrosine kinase domains of both the HER2 and HER1 receptors.   Because lapatinib inhibits two cell surface receptors and is a smaller molecule than trastuzumab, the hope was that it may prove to be more effective when combined with trastuzumab through the two agents’ different mechanisms of action, achieving dual HER2 blockade.

Dr. George Sledge Jr., former President of ASCO, Discussant for Plenary Session on the ALTTO Trial Results

Dr. George Sledge Jr., former President of ASCO, Discussant for Plenary Session on the ALTTO Trial Results

This led to the development of the ALTTO trial, comparing use of trastuzumab alone against the combination of trastuzumab and lapatinib and, ultimately, the findings that there was no significant difference when lapatinib was added to treatment.  Dr. Sledge emphasized that the ALTTO trial required a strict P value of .025 or less to demonstrate statistical significance, and he stressed that no one should be misled by the disease-free survival P value of .048, thinking that this was a positive trial.  Rather, he firmly stated that “This is a negative trial.”  He then posed the important question of whether this trial might later turn statistically positive with further follow-up based on additional results.  His response: “Perhaps, but not very positive, given the results we’ve seen today.”

The negative results of the ALTTO trial were surprising due to the positive results of the earlier NeoALTTO trial, a study in which lapatinib and trastuzumab were compared with trastuzumab alone in the presurgical (neoadjuvant) setting.  Treatment with lapatinib, trastuzumab, and paclitaxel (Taxol®) was found to nearly double the pathologic complete response rate (pCR).  (Pathologic complete response, or no invasive or in situ residuals in the breast or lymph nodes, is proposed as a surrogate endpoint of tumor response that should be strongly correlated with more traditional endpoints such as overall survival and disease-free survival.)

These results are not only extremely disappointing based on lack of improvement with this specific combination therapy; rather, they also raise troubling questions on the approach to the development of new drugs for early breast cancer.   As Dr. Sledge noted, these negative findings “tell us at a simple level that we won’t be using lapatinib in the adjuvant setting,” since as discussed above, he predicts that further follow-up of the ALTTO trial results will not lead to a statistically significant positive result.   But he also stressed that these findings have produced several larger, critical questions: “You might be wondering why a negative adjuvant trial occupies a Plenary Session spot, a place usually reserved for practice-changing data.  I suggest that the answer requires us to rethink our approach to the development of new drugs for early breast cancer.  ALTTO represented a reasonable test of the hypothesis that improvements in pathologic complete response rates were associated with improved disease-free survival.  These hopes have now been dashed.”

Said another way, in recent years, many breast cancer researchers, clinicians, and advocates have become increasingly comfortable with the idea of conducting innovative, smaller neoadjuvant clinical trials, using pCR as a surrogate endpoint to predict outcomes  in the adjuvant setting.  Yet the negative results from the ALTTO trial, following the positive results from its sister neoadjuvant trial, NeoALTTO, serve to undermine confidence in the accuracy of predicting and translating treatment effectiveness and outcome from one clinical setting to another.  As Dr. Sledge noted, the ALTTO trial “invites a larger question” of whether agents that are found to be effective in the metastatic or neoadjuvant settings can be considered predictive of similar efficacy as adjuvant treatments.   “Why have these approaches failed in the adjuvant setting, despite a plethora of preclinical evidence and numerous positive trials in the metastatic setting that show an overall survival advantage?  These setbacks should prompt us to ask, are we facing a systemic crisis in the adjuvant failure of targeted therapies or just having a string of bad luck?”

ErbB family of receptors

ErbB family of receptors

Dr. Sledge went on to emphasize that results from another large adjuvant trial, called the APHINITY trial–which is also studying the efficacy of dual HER2 inhibition versus use of a single anti-HER2 agent–will be of great interest in light of ALTTO’s negative results.  APHINITY is a large Phase III randomized, double-blind, placebo-controlled trial that is comparing the efficacy and safety of chemotherapy, trastuzumab, and placebo against chemotherapy with trastuzumab and pertuzumab (Perjeta®) as adjuvant therapy in patients with HER2+ primary breast cancer.  Like trastuzumab, pertuzumab is a monoclonal antibody that targets the HER2 receptor, but it binds to a different part of the HER2 molecule and thus does not compete with trastuzumab.  Pertuzumab prevents the pairing (called “dimerization”) of HER2 with other HER (ErbB) receptors (HER1 [EGFR], HER3, and HER4), particularly the pairing of HER2/HER3, blocking the signaling pathways within the cell that lead to tumor growth.

 

And in fact, as I wrote in a previous blog posting, “All eyes will indeed be on the large adjuvant APHINITY trial …,” because last year, for the first time for any cancer, FDA approval was given to an oncologic agent—i.e., pertuzumab– in the neoadjuvant setting, based on pCR as a primary endpoint.  This was in no small part because of the ongoing, fully accrued APHINITY trial, whose results, if successful, could support conversion to regular FDA approval or, if negative, will even further emphasize the need to completely re-evaluate our current approach to drug development and clinical trials for agents to treat early breast cancer.

On this last point, when the Oncologic Drugs Advisory Committee (ODAC) voted on whether to support Accelerated Approval for pertuzumab in combination with trastuzumab and chemotherapy for neoadjuvant treatment of HER2+ breast cancer, many ODAC panel members (including myself as the patient representative on the panel) stressed a critical point: that if the results of the APHINITY trial were in fact negative, the sponsor, Genentech, should voluntarily remove pertuzumab for the neoadjuvant treatment of early-stage breast cancer.  As our committee chair, Dr. Mikkael Sekeres, emphasized to the FDA, “All eyes will be on the confirmatory APHINITY trial and on you to verify this initial signal of efficacy and to confirm the bandwidth of safety that we have seen so far.”

In light of the ALTTO findings, APHINITY’s long-awaited results will now carry even more impact, whether they are positive or negative.  In concluding his discussion, Dr. Sledge emphasized that trial failures such as ALTTO “must be elucidated in order to move forward and create new successes.”

At this writing my cousin has received two treatments thus far with chemotherapy, trastuzumab, and pertuzumab.  And in her husband’s words, per her oncologist’s first assessment of her response, “the couple centimeter lump of cancer on her neck” (which had resulted in her stage IV diagnosis) “has gone away.”  I pray daily that this means she is a strong responder to dual blockage with trastuzumab and pertuzumab.  I pray that some day she’ll hear the words that her stage IV breast cancer is now “NED,” meaning No Evidence of Disease. And I pray that in the words of Dr. Sledge, “ … Move forward, we shall, in HER2+ positive breast cancer” and that the many novel approaches actively being researched today will move us closer to the day when we have finally found a cure or cures for stage IV breast cancer–for my cousin, for my far too many friends with this disease, and for all those with stage IV disease.  Please pray with me.

Preserving Hope: Our Caregivers’ Journeys in the World of Cancer

Many folks might not understand this.  But I’ve lost track of how many times I’ve thanked God that I  and not one of my loved ones was the cancer patient.  After being diagnosed with lymphoma shortly after college, cancer shaped my life.  As I’ve said many times, being a cancer survivor has impacted every adult decision of my life: staying in a job that I disliked far too long due to fear of being without health insurance, my decision to become a medical writer, when to get married, and on and on.   But I’ve had to be matter-of-fact about this.  Cancer, its late effects, what seems like my bimonthly thyroid biopsies, the number of daily pills I’ll always have to take, my long list of specialists—it’s simply my reality.  But that’s okay.  Long ago, I subconsciously made this one of my roles: I took on the role of cancer patient, the one with the chronic health issues in my family, with the understanding—or perhaps more accurately stated, the magical thinking—that I gladly accept this role to protect any of my loved ones from EVER experiencing cancer, cardiac issues (another of my late effects), or any serious chronic health issue.  My message to myself was “I’ve got this.  I’ve got my family covered.”

Magical Thinking

My mother helped me to understand this at a more conscious level just last year, one which was  very difficult for my family.  I have two female first cousins, one on my mother’s side and one on my father’s side—and in one year, they both were diagnosed with stage 3 HER2+, ER+ breast cancer at the age of 49.  I was never angry about my own cancer diagnosis: the first time, my thought always was, “Well, why NOT me?,” and the second time I’d long understood that I had a greatly increased risk for breast cancer due to my radiation treatment as a young woman.  But when I learned that my first first-cousin had just been diagnosed, I was distraught and absolutely furious.  I literally screamed when I heard the news.  And when I learned a few months later that my second first-cousin had been diagnosed as well, my anger and distress were even blacker and deeper.  I couldn’t understand my reaction, and I pushed it down deep, because it was critical to me to be strong for my cousins and able to have my “advocate hat” firmly in place to provide all the possible information, resources, and support I could for them both.  But in talking with my mother one day, I shared with her how deeply furious I was that they were both going through this and how confused I was about feeling this way.   She said that she had the answer, asking “You don’t remember what you said to me, do you?”  Of course, I’m notorious among my family for not remembering anything (thank you, “chemobrain” parts 1 and 2), so we chuckled over that.  She then explained that shortly after my breast cancer diagnosis, she’d asked me why I wasn’t angry about being diagnosed now for a second time.  And she reminded me of my answer: “You said that as awful as it was, you knew you’d get through it, and you weren’t at all angry because, after all, that must mean that you had the family covered.”

Downcast

And that’s true: I continue to pray every day that that’s IT—that cancer has learned now who’s boss and will not DARE touch another of my loved ones.  This may explain why I was so struck by something a fellow cancer survivor and advocate said during a panel discussion last year, where we were both participating as Patient Advocate Fellows during the Drug Information Association (DIA) annual meeting.  When my new friend and colleague, Deborah Cornwall, began her portion of our panel’s presentation, she explained that she was a breast cancer survivor, but that her own “brush with cancer was trivial” compared to the caregiver and patient stories she’d had the honor of hearing while working on her recent book, “Things I Wish I’d Known: Cancer Caregivers Speak Out.”  She explained that although there were so many books for the cancer patient, as there should be, there were very few for the cancer caregivers–for the spouses, the parents, the children, the siblings.  As Deborah discussed her book, its purpose, and the meaning that it had for her and the many caregivers she interviewed, I was deeply moved, thinking about just how important this book was—that in addition to the patients themselves, it’s just as critical that the loved ones who are caring for them receive the support they need and how cancer also turns their worlds upside down.

A few weeks following the conference, Deborah graciously agreed to an interview, during which I asked her about the genesis of her book, any critical overarching themes that arose while speaking with the caregivers, and the experience itself of speaking with so many people about what was often the most heartbreaking time of their lives.  Following is some of the conversation that Deborah and I had, including several quotes from Deborah and the caregivers themselves.

Cancer Caregivers Speak Out

“Why do people love firemen? People love firemen because when everyone else is running out of a burning building, they’re running in.  It’s easier to run away.  Caregivers are running into the burning building…”

~Chuck’s Mother

In the introduction of Deborah’s book, she shares the following, describing the beginning of the caregiver journey:

“Most caregivers describe their reactions to a loved one’s cancer diagnosis in violent terms: a fast-moving or violent physical assault, a punch in the stomach, a car hitting a deep pothole at high speed, a hijacking, an earthquake, a lightning strike, or a vicious animal bite.  A few mentioned a sensation of being frozen and unable to move, or feeling as though a rug had been pulled out from under them.

“If you have been suddenly thrust into the caregiver’s role, you may have experienced similar sensations when a loved one or close friend received the cancer diagnosis.  There’s so much information coming from all directions that you may feel overwhelmed, angry, or bewildered. ‘Normal’ has just disappeared from your life.  You may be fantasizing that you’ll wake up tomorrow and find out that this was all a bad dream.  You may even feel resentful: After all, you didn’t sign up to set your own life aside to become a caregiver.

“Your emotions are real, and confronting them is the first step in coming to grips with your caregiver role.  You’re probably wondering how this unexpected journey will go, and how it will end.  You may be looking for support, guidance, or help—perhaps for the first time in your life—at the same time that you’re uncertain where to look, or even what to ask for.

“That’s another reason why I’ve written this book.”

“In reading about the key issues you’re likely to face and what others did when encountering similar situations, you’ll have the opportunity to learn from their approaches and use them in creating your own solutions to your unique caregiving challenges.  While this book won’t serve as a complete ‘how-to’ guide or steer you to every resource you might need—caregiving often requires invention under pressure—it will provide guidance and build your confidence in inventing your own way.

“I was honored that the people I interviewed chose to share their stories and life lessons.  Their candor and intimacy were unexpected gifts that enriched my life immeasurably and made this book a reality.  In turn, I share their reflections with you in the belief that they will help you on your journey.  Their hard-earned insights, their indomitable hope, and their desire to help others to stay focused in the face of adversity represent their way of giving something back to those who helped them.”

~Deborah Cornwall, Marshfield, Massachusetts, 2012

~~~~~~~~~~~~~

Our interview began with Deborah’s sharing how “Things I Wish I’d Known” came to be:

“Writing a book of some sort actually came from my aunt, who is 95 years old now.  So she was about 91 when the idea came up.  I was talking with her about various experiences that I had had at Hope Lodge, [which provides] free lodging for cancer patients and their caregivers who come in from more than 30 miles away for regular care for cancer treatment…I had been involved on the American Cancer Society Board of Directors in New England when we decided to build the [Hope Lodge in] Boston.  I kind of adopted it personally.  My husband and I would go there periodically to serve holiday meals, because our daughter lives elsewhere and can’t always be with us.  While there, I would always meet people whose stories were just amazing and far more dramatic than my own.  Afterward, I would share them with my elderly aunt on the telephone.  Then one day, she said, “You have got to write a book” … I kind of pooh-poohed it, because your relatives always believe you can do anything.  But a few weeks later, after the idea had had time to germinate,  I realized she was right.”

Hope LodgeIn thinking about the shape that the book would take, Deborah realized that there were few books that specifically focused on the stories of the cancer caregivers, how they coped, what resources were most helpful to them, and, upon reflection, what they wished they had known beforehand but learned only in the midst of their experiences as a caregiver.  So that is the book that she wanted to create.  Deborah noted, “That’s when I charged off on my own and said, ‘Okay, I need to find people who are willing to talk to me.’  She explained that with HIPAA (the Health Insurance Portability and Accountability Act) privacy regulations, “that’s a bit tricky.  So I needed to spread information out in the right places and let people know how to contact me if they were interested in talking about their experiences.”

ConnectionsDeborah stressed that the sourcing of interviewees was itself a fascinating process.  “I think the most interesting piece of it was that in addition to posting invitations at several of the Hope Lodges, I would also send out waves of emails to groups of my own contacts,  asking them to spread the word.  I got a phone call one day from a woman who had received my email, which I’d sent to someone out of state, who forwarded it to somebody else in another state, who in turn forwarded it to the woman who called me.  It turned out that on the third forwarding, it went to [this woman] who lives five minutes from my house!  Isn’t that bizarre?  So there are all sorts of fascinating procurement stories in terms of finding these people.”  Deborah went on to share another example of such serendipitous connections: “I received a phone call from a woman who had just lost her husband.  [She’d been] in a park walking with her daughter and newborn son, and a friend of mine happened to be passing through that city when they met and created the connection.  This woman has sustained our relationship and become a good friend. There were all sorts of really random types of connections, but essentially, when I got to 86—and there was nothing magic in the number–I thought to myself that I’m hearing the same things frequently enough that I believe I have enough to work on.  So that was the genesis.” In the second edition of the book, Deborah added another nine conversations focused on healing, bringing the total to 95.

Deborah emphasized how moved she was that so many caregivers were willing to speak with her for her book.  “I was stunned at how eager people were to talk and how much they wanted to share with me, usually as a complete stranger.  Two-thirds to three-quarters of the caregivers were complete strangers with not even a personal referral connection, not even a mutual friend . It was really stunning to me how eager they were to pour out their most intimate life stories.  And what it said to me once I got going was just how important they thought the book could be.”  She also noted that during their caregiving experiences, “some of these caregivers were deserted by people they thought they were close to.  So I think that in some ways, that made them want to talk about it more, because family members or friends didn’t know what to say and didn’t know how to have a conversation about what the caregivers were going through.  In a way, to talk to a stranger who really wanted to know what happened was nourishing to them.  After one particularly moving conversation, one interviewee said he felt better because it felt as though he’d just been to therapy.  It had presented the opportunity to voice things that he’d kept inside since his wife had died. I think that the interviews did allow people to get in touch with how they had really navigated the experience when maybe they really hadn’t had the opportunity to reflect on it before.”

In fact, folks were so open to speaking with Deborah about their caregiving experiences that her first interview for the book occurred even before she thought she was prepared.  “My first interview was with a woman I’d known for years who was on the staff of the American Cancer Society.  Just before a scheduled meeting started, I [mentioned] to her that I was writing a book on caregivers. Her immediate response was, ‘Oh, I’m a caregiver.  Talk with me!  I have time right after the meeting is over.’   My first thought was, ‘So soon? I haven’t even finished the interview guide yet!,’ but I did it.  Her story was a rich one. She had been the primary caregiver for her father, who was dying of cancer, and at the same time for her mother, who was having a nervous breakdown. My friend was a single mother of two young children, she had two siblings who were uninvolved, and she was trying to work at the same time.  At one point, I asked her, ‘Where were your siblings?  Did they ever ask how you were doing during this whole process?’  It took her several minutes to respond. Then she looked at me with these wide deer-in-the-headlight eyes, and all of a sudden, tears started rolling down her face.  That’s when I realized that I was on to something really important.”

Deborah shared that when she completed and submitted the initial draft to her professional editor, his feedback was positive, yet she was taken aback when he stressed that, ‘It’s only twice as long as it can afford to be to get read.’  She stressed that pruning down the stories she shared was an extremely emotional process for her, because “I feel like I still carry their stories with me all the time.  They shared so much of themselves that I really felt that I owed them to tell their stories.”

Overarching Themes Expressed by Caregivers

When I asked Deborah whether any themes emerged when speaking with family caregivers, she noted that there were several:

“Yes, the first was control, a theme that really permeated every conversation:  the feeling of loss of control.  As you grow up, you develop a profession, you buy a house, you get married, and somehow you start believing that you actually have some control over your life.  Then, all of a sudden, when you’re told that you or a loved one has cancer, that sense of control is gone.  That theme was particularly significant for some of the male caregivers.  I had a couple of them who described themselves as control freaks who had to learn to let go of the fiction that they had any control.

“The second theme was the need to somehow preserve hope and, even for those who were told that they were in very dire straits, to see their situation in a more positive light.  When one was told that x percentage of people only survive a certain period of time, she and her husband said, ‘Fine:  we’ll be in the other percent.’  Even if it was a mind game, these caregivers found some way to create some hope in the situation, but also to make sure that today was a joyful day, that there was something today that I could do to help the person not just get through the day, but really enjoy the day.  And for many of them, that was hard.  But you know, there were several stories of people dying at home, where even the death experience was turned into something that would feel positive and in their control, as opposed to being in a hospital, where you couldn’t control who was coming in and giving you shots and doing all sorts of things.

“The third theme was isolation–the feeling that so many of the caregivers had of being cut off from the people they used to see often. I called those people ‘pull-aways,’ the friends who didn’t know what to say or do, and so didn’t talk about it or didn’t make contact as they might have back before the cancer diagnosis.  And there were some situations where the patient was too sick to go out, and so the caregiver’s solution for overcoming isolation was to invite friends in, but to be very clear about when it was time for them to go.  The caregiving experience changed caregivers’ social patterns, but they really felt its absence unless they invented new ways to interact with friends.

“[Another important] piece was normalcy.  People wanted so badly to get back to normal, and yet there was never going to be a normal again. Maybe a new normal would evolve, but life would never go back to the pre-cancer world.”

Deborah also noted that when reflecting on their experiences as caregivers, “All noted that their caregiving had enriched their lives.  It really did.  And I was really surprised when I asked them, ‘How are you different?’ I just didn’t know what I was going to hear.  It was encouraging and also really striking how many of them engaged in an activity that will in some way give meaning to their caregiving experience, particularly if their loved one died.  Even though this matched my own experience, I didn’t realize just how widespread that giving-back phenomenon would be.  Sometimes it’s focused on a specific type of cancer, such as leukemia or lymphoma.  Sometimes people actually created a new foundation, like two caregiving families living next door to one another who together created a brain tumor organization to benefit a local hospital, for example.  It’s fascinating to hear the creativity people use in determining how to get involved and how they want their loved one either to be honored or remembered.”

I asked Deborah if hearing such emotionally trying, heartfelt stories was ever difficult for her both as an interviewer and as a cancer survivor herself.  She agreed that it was:  “A couple of times, I did break up on the phone, and I apologized.  But I found it didn’t matter to the interviewee.  In fact, it revealed that I cared.  I always felt self-conscious about it, but it turned out to be okay.  To have them talking about the last minutes of somebody’s life and to be able to do so in such a loving and really clear descriptive way, it was hard to imagine putting myself in their shoes and being able to have gone through what they experienced with as much grace.  They really all gave a tremendous gift to me and to anyone who reads the book, because of the raw emotions that they shared.  Equally riveting were their descriptions of their lives afterwards and how they have healed.  I’ve actually written an article about healing and added some of these insights into the second edition of the book, because I think it’s really helpful to those who are still going through the process.”

Starting the Healing Before the Caregiving is Over 

“One of the important things I learned was that people who do it well start the healing process before the caregiving is over,” Deborah stressed.  “And in fact, in some cases, the patient actually helps start that process.  One young man whose mother died described one of her last days, [when she gave] him instructions about how she wanted to be buried.  She asked him to make sure that she was wearing nothing but her full-length mink coat and red high heels!  And that’s what he did.  He can still laugh now when he talks about it, because it was such a funny funny request and reflected so much about her personality.  The other thing she had done that was so fascinating: as an experienced oncology nurse, she surrounded him with many of her nurse friends, so that if he ever had any questions as she was going through treatment, he had this network that could be a safety net for him.  There were several examples of patients who had done something like that.  It turned out to be really important to each caregiver’s healing later.”

The Keys

I couldn’t let Deborah go without asking her about the cover design for her book.  As shown below, the cover displays three large, antique keys that immediately grab the eye.  She explained that “I’d looked at several alternatives, [but] this was the one that struck me.  I think that the keys have meaning in the sense that … it’s almost like there are trap doors throughout the caregiving process.  And knowing what door to open and which key to use, it was almost an analogy of finding answers–‘What’s behind this door? What’s behind that door?’ There are hidden things that you need to find out behind each door.  The key design was really the message of the book and the best way to show it.  Somehow it spoke to me.”

Things I Wish I Knew

Messages from the Caregivers

What better way to conclude than sharing the words of some of the caregivers from “Things I Wish I’d Known: Cancer Caregivers Speak Out”?

“Professional caregivers don’t experience the emotional ups and downs that a family caregiver does.  The family caregiver truly bears the brunt to support the patient in the right ways, not too much or too little.  It’s critical for the patient’s progress.”

~Ellen M, registered nurse and cancer survivor, sharing her perspective on the role of her husband as  caregiver

“Caregivers have a difficult emotional time.  They don’t face the daily adrenaline surge that the patient does, but they have to pick up the pieces when things aren’t going well.  It’s hard for them to know when to reach in and when not to.  They walk a tightrope between letting the patient be in control and being able to take care of them without letting their loved one feel incapacitated.  Caregivers haven’t experienced the physical pain, but they also can’t make it go away.  The caregiver has to be strong, but not overpowering; sympathetic and optimistic, but not saccharine; realistic but not discouraging; upbeat but not inappropriately happy.”

~ Bobbi, long-time breast cancer survivor, articulating the challenge of caregiving

“There’s no better way to learn about dealing with cancer as a caregiver than hearing other people’s stories.”

~ Debbie B’s husband

~~~~~~~~~~~~~~~~~~~

The Book

Interested readers can locate Deborah’s book in paperback or electronic forms at the following websites:

“Things I Wish I’d Known: Cancer Caregivers Speak Out”

Amazon.com

Barnes & Noble

“A New Layer of Pain” for Our Newtown Community

This morning began with a very upsetting bit of news.  I’d been mercifully away from the U.S. news for a few days, having been in England.  As a cancer research advocate, I’d had the honor of serving as a panel speaker during a joint European Medicine Agency (EMA)/Clinical Trials Transformation Initiative (CTTI) session in London. ( But more on that in a future blog …)

While I was away, it turned out that we also had trouble with our cable TV.  So this morning, while still bleary-eyed from jet lag, I talked to the cable company, managed to get the snafu resolved without too much frustration, and then turned on the TV to catch up with the news while having my morning coffee … and was immediately upset by the very first news item I heard.  Like many of you, I suspect, I find most of today’s news infuriating, sad, or tragic.  But this news item was personally upsetting to me and undoubtedly to many in my Newtown community:  I learned that the Sandy Hook 911 tapes were released today, following a ruling by a Connecticut state judge:  i.e., just 10 days before the “one-year anniversary” of the tragic events that occurred here in Newtown on December 14, 2012.   And the fact is that most of us here have been absolutely dreading the arrival of 12/14, fearing the repeated onslaught of media, the horrifying memories that remain all too raw, and the renewed grief for all those who have been irrevocably affected by this terrible tragedy.

I almost always agree with the sentiments of Newtown’s First Selectman, Pat Llodra–and that’s the case once again.  In response to the news that the tapes were being released today, she stated that this would only serve “to create a new layer of pain for many in the Newtown community.”   Some folks throughout the country have argued that releasing the tapes to the AP would be a matter for the “public good.”  And the judge who ruled to release the tapes noted that doing so could help by “showing the professionalism of the first responders and pointing to anything that might be done differently in future emergencies.”  But my own response to that is, Was the professionalism of the first responders ever in doubt?  If so, I’d find that absolutely shocking, since to a person, I’ve heard nothing but a world of respect, awe, and admiration for the first responders who served the people of Newtown and Sandy Hook that day.  And “what might be done differently”--or, said another way, what should be changed?  The official investigation examined these questions up, down, and sideways, as it should have: those few questions that could be answered were, and the investigation is now closed.  And most would agree that following the events of that terrible day, in pondering the imponderable, our towns, cities, states, and federal government–our society overall–has already been profoundly changed in countless ways (for better or worse or both?), whether looking at the subject and tenor of our ongoing national conversation on violence, increased spending in the last year on mental health in most states and implementation of measures to make treatment more accessible for children and adults with mental illness, additional security changes put into place, new gun-control legislation proposed, and on and on and on.

Judge Eliot Prescott

New Britain, CT Superior Court Judge, Eliot Prescott, Rules That He “Will Listen to Sandy Hook 911 Recordings”

So what is there to gain by listening to these horrific events as they unfold, by graphically hearing the very voices of those who lived–or tragically, did not live–through them?  As a Newtown resident who loves my community, I would argue, Nothing, except for renewed pain and heartbreak.

To read the eloquent words of Pat Llodra in response to the release of the 911 tapes, simply click here:  PERSONAL REACTION TO THE RELEASE OF THE 911 TAPES – December 4, 2013; Pat’s Blog: One Newtown.

Moving Us Forward

Before the 911 tapes were released, Pat reflected on how those in our Newtown community will be handling the arrival of December 14th: “Our community is choosing to remember and honor those who lost their lives in that awful tragedy in ways that are quiet, personal and respectful — centered on the themes of kindness, love and service to others.”   My hope is that everyone will understand and honor Pat’s thoughts and wishes for our Newtown community.

On the Meaning of Birthdays to a Cancer Survivor (aka “My first 49th?”)

When I was growing up, birthdays were always of tremendous significance in my family.  My sister and I both looked forward to our own special days all year: we loved the presents, the attention, the parties, everything about it.  But maybe most of all, we loved the excitement of finally seeing the theme my mother chose for our birthday cakes.  She always made complex cakes of her own special design, and she outdid herself every year.  We still talk about the most memorable one: the “Bucky Dent” cake, designed to look like my sister’s large blue, buck-toothed stuffed rabbit that she’d named in honor of the (very!) handsome Yankee short stop.  As a kid, I also loved that my birthday came just a few days before Halloween.  I was a painfully shy little girl, but I loved dressing up to be someone (or something) else, the spookiness of it all, seeing all the other kids’ costumes in the neighborhood, and eating far too much candy for several days.

Celebrating my 4th birthday with family and friends

But I figured that when I “grew up,” birthdays would become just another day.  And that’s definitely the case for my husband.  As one of 9 kids in an Irish-Catholic family, his parents (understandably!) didn’t have the time or energy for big birthday celebrations, particularly by the time Marty arrived (the 8th child and youngest boy).  He does reminisce about how his mother would let the kids choose their favorite meals for their birthday dinners and how that was always such a treat.  But now he encourages me NOT to get him anything for his birthday (I don’t listen) and, last year for his 50th, NOT to do anything, let alone anything special (I didn’t listen).  And just this week, when I asked if he minded that I’d be attending a grant review panel on the day of his birthday, he started laughing … “Oh my God, Deb: I’d be absolutely devastated! “Nuf said. :-)

But the fact is that every year when the calendar reaches October 27th again, I take time to reflect–and to appreciate just how fortunate I am to BE here.  Most young adults still have at least a residual sense of invulnerability that’s hung on from childhood and adolescence:  from simply not understanding the concept of death to not being able to comprehend one’s own death, a feeling that death “can’t happen to me.”  Yet at the age of 22 years, I lost my sense of invulnerability for a lifetime.  It literally was a black-and-white moment, during which my childhood doctor and I were looking at my chest x-ray, showing one lung that appeared black (as it should have) and the other covered entirely in a frosty white.  The cause, stage III Hodgkin’s lymphoma–a diagnosis that if received just a decade before may very well have meant that I wouldn’t be celebrating many more birthdays.

And on Halloween night this year, my memories returned of another moment that similarly divided time for me.  Exactly 10 years ago, 4 days after my 39th birthday, I learned that I was facing the real possibility of not being here to celebrate my 40th.  On that Halloween day in 2003, I was walking up the stairs to my new cardiologist’s office, fighting the pain gripping my chest and stopping every few seconds to catch my breath. Once I reached the office, I carefully settled myself into a chair in the waiting room and watched in a daze as members of the office staff went about their business, all while dressed in Halloween costumes.  Normally, I would have gotten a kick out of that.  But not on that day.  I was still trying to catch my breath when the technician who had performed my cardiac testing walked right over to me, put her hand on my shoulder, leaned over, and asked if I was okay.  She then clasped my arm warmly, smiled, and went to her next patient. She was in costume as well, a frightening one actually, but the fact that she obviously recognized my fear, comforted me, yet didn’t say, “don’t worry; everything is going to be fine”–that was one of the scariest moments of my life. And it wasn’t fine.  Instead, I learned that I had 90% blockage of one of my coronary arteries.  The cause: scarring and narrowing caused by my radiation treatment for lymphoma several years before.  And, as I’ve written about previously, because of the location of the blockage, I faced a terrifying decision–whether to proceed with an angioplasty, which presented the risk of another coronary artery collapsing and a heart attack during the procedure, or whether to go right to open-heart surgery for a coronary artery bypass graft.  When I later found myself asking the cardiologist whether I should be thinking about “getting my affairs in order,” I was shocked on so many levels: that I was actually asking this question, how truly surreal the situation was, and worst of all, to hear that the answer was “Yes.”

As a young adult cancer survivor (AYA), I know that the reality is a stark one for far too many of us.  According to the National Cancer Institute (NCI), unlike overall improvements seen with older adults and younger children, the survival rates for young adults with cancer have not improved in nearly 30 years. The lack of improved outcomes can be due to a number of factors, including delayed diagnosis (since many MDs may rarely consider the diagnosis of cancer in a young adult), lack of health insurance and limited access to medical care, receipt of treatment that may not be most effective for their cancers due to limited understanding of the biology and etiology of cancers in AYAs, and the unique supportive and psychosocial care needs that come with such a diagnosis at the juncture between adolescence and adulthood.  And of course, there’s the fact that AYAs face a substantial risk of developing serious late effects of their cancer treatment, including cardiotoxicity and second primary cancers–which, in my case, includes my breast cancer diagnosis at the age of 42 years, also thought to be secondary to my radiation).

So coming full circle, although it may seem childish, I treasure my birthdays because I’ve been given the gift of still being here.  This year’s was my 49th–and next year, I won’t be describing it as my “second” 49th.  I’ll be thrilled that I’m here for 50 and for every day before and after.

October 13th, Making Awareness Meaningful with National Metastatic Breast Cancer Awareness Day

Today is October 13th, the 286th day of the year, a day in history when the first electron micrograph was taken of the deadly Ebola virus (1975), when Jordan joined the Yom Kippur War (1973), and when the rock legend Neil Young had throat surgery (1975).  To my mind, this day in history is actually one of the most important on the calendar—because in 2009, it was designated as “National Metastatic Breast Cancer Awareness Day” by the U.S. House and Senate, thanks to the dedication and passion of the Metastatic Breast Cancer Network (MBCN)’s legislative advocacy team.

National Metastatic Breast Cancer Awareness Day Proclamation

The purpose: to draw attention to the unique and often unmet needs of the women and men in the United States who are living with metastatic breast cancer.  As noted by Dr. William Gradishar, Northwestern University Feinberg School of Medicine, on the Metastatic Breast Cancer Network’s website, “While there is no cure for metastatic breast cancer, some individuals are able to live longer with the disease.  However, metastatic breast cancer remains a clinical challenge in the oncology community.  October 13 places emphasis on the disease stressing the need for new, targeted treatments that will help prolong life.”

National Metastatic Breast Cancer Awareness Day

This day provides a critical opportunity to clear the misconceptions that far too many people have about breast cancer.  First and foremost, do you remember when 2012 Congressional candidate Chris Collins of NY was quoted as saying, “People now don’t die from prostate cancer, breast cancer and some of the other things”?  Yes, he really said that.  But as atrocious as this was, the sad truth is that some folks do believe this—and worse, some essentially blame the patients themselves with metastatic disease, particularly those with breast cancer, thinking, “She must not have gone for her mammograms.”  To which I say, “wrong and wrong: wrong, wrong, wrong!!!”  The truth is that despite increased use and access to mammograms and some treatment advances, approximately 40,000 Americans die from metastatic breast cancer every year.  And despite earlier and earlier diagnosis of ductal carcinoma in situ (DCIS), also known as “stage 0,” precancerous, or preinvasive breast cancer, the incidence of metastatic disease has not significantly declined.  Another truth: Mammography screening does NOT prevent nor cure breast cancer, but we do know that it can lead to overdiagnosis and overtreatment.  And yet another truth: Not all breast cancers are the same.  Some breast cancers are extremely aggressive, growing and spreading rapidly, and may not be effectively detected with screening mammograms.  Others are more slow-growing and may be more easily found on mammography, yet may never have become invasive or life-threatening.  Rather, there are many different forms of breast cancer, based on the biology of the tumors and the microenvironment surrounding the tumors—with each subtype having a different prognosis and responding differently to specific forms of treatment.

MBC Awareness

National Metastatic Breast Cancer Awareness Day promotes the type of awareness that is truly meaningful–by pushing aside all the pink ribbons (and pink blenders, guns, oil delivery trucks, and …) and revealing the important truths behind the pink curtain.  So today, as my way of honoring all of those affected by metastatic breast cancer, I encourage you to:

* Read The 31 Truths About Breast Cancer, one truth for every day of October

* Read “Thirteen Things Everyone Should Know About Metastatic Breast Cancer”

* Help to increase awareness of the truths that matter by:

Sharing the 2 links above with your family, friends, and colleagues.

Sharing the MBCN’s “Grow Awareness. Share Support. Metastatic Breast Cancer Awareness” page on your Facebook page, your Twitter account, and your Pinterest page.  Every time you do so, AstraZeneca will make a donation to two metastatic breast cancer advocacy groups: Living Beyond Breast Cancer and the Metastatic Breast Cancer Network.

Grow Awareness of Metastatic Breast Cancer

* Visit the websites for the Metastatic Breast Cancer Network, Living Beyond Breast Cancer, AdvancedBC.org, BrainMetsBC.org, and the new Metastatic Breast Cancer AllianceAnd please share information and links on my blog concerning additional organizations that are dedicated to the unique needs of women and men with metastatic breast cancer.

And please help me honor:

* the so many wonderful women and men we’ve lost to metastatic breast cancer,

* the far too many of my beloved friends and the tens of thousands in the U.S. and more across the world who are living with metastatic disease,

* and all those who are dedicating their lives to supporting women and men with metastatic breast cancer and who are tirelessly working to find the causes, enhanced treatments, and cure.

A Historic Moment: First Pre-Surgical Drug Approved for High-Risk Breast Cancer

As far too many of us know, a diagnosis of breast cancer is shattering, frightening, overwhelming … a maelstrom of one emotion after another.   And while trying to come to terms with this life-altering diagnosis, many of us have found that we’re confronting a new language where pathologic terms and molecular subclasses, the biology and behavior of our breast cancer, are driving our treatment options, our choices, our prognoses.

Shortly before I learned that I had breast cancer in 2007, patients diagnosed with what is known as HER2+ breast cancer were told that their cancers were very aggressive and that their prognoses were poor.  Normally, the protein known as “HER2,” a receptor on breast cells, helps to control breast cell growth, division, and repair.  But in those with HER2+ breast cancer, more than the two copies of the HER2 gene may be present, leading to overproduction of the receptors on the cell’s surface, HER2+ overexpression, and uncontrolled breast cell division and growth.  The day that I finally gained the courage to read my pathology report after my surgery, I was aware of this–that HER2+ breast cancers were considered more aggressive, tended to grow and spread more rapidly, and were less responsive to certain therapies when compared to other breast cancer subtypes.   And though I already knew that my tumor was found to be estrogen-receptor positive (ER+), I didn’t yet know my HER2/neu status.  Either that conversation with my surgeons had taken place during the drug-induced haze immediately following my surgery, or it hadn’t happened yet.

HER2+ breast cancer, Perjeta Patient Information, Genentech

As I turned the pages of my pathology report, I registered that the estrogen receptors were 62%–and that a higher percentage would have been considered “better,” but that this was still considered “good” prognostically.  When I saw 0% for progesterone receptors, I recognized that that actually wasn’t so “good”:  after all, it was labeled right there on the report as of “unfavorable prognostic significance.”  But it was the next line that I was most nervous about:  and there it was, my HER2/neu status … and it was “Negative.”

When I saw this, I did feel something akin to relief—though as I learned not long after, there is nothing clear-cut about breast cancer.  On that January afternoon in 2007, should my tumor’s HER2 status have been positive, I actually would have been in a much better position than women diagnosed just a few short years before my own diagnosis.  The fact was that recent advances had offered a critical new treatment option for patients with HER2+ breast cancer.  Just 2 months before, in November of 2006, trastuzumab (Herceptin®), a targeted biologic therapy, had been approved in the postsurgical (adjuvant) setting for early-stage HER2+ breast cancer (BC).   I was correct in my understanding that HER2+ disease is a particularly aggressive form of BC—and that because of the aggressiveness of breast cancers that overexpress the HER2 protein, patients with HER2+ disease have an increased risk of recurrence and decreased survival compared to those with HER2-negative disease.   But the development and approval of trastuzumab was truly a dramatic breakthrough for the treatment of HER2+ BC, both in reducing recurrence risk for those with early disease and increasing overall survival for patients with metastatic disease.  In fact, when the combined results of the adjuvant BC trials were presented during the American Society of Clinical Oncology (ASCO)’s 2005 Annual Meeting, the audience greeted the news with thunderous applause and a prolonged standing ovation.

Those who jumped to their feet when hearing the news about trastuzumab recognized this targeted therapy for the critical breakthrough that it was, one that has since changed the natural history of early HER2+ BC.  And yet …

Though trastuzumab and other targeted therapies since approved for breast cancer–and other cancers– have led to remarkable improvements in response to treatment and survival for some, resistance to targeted treatment, both intrinsic and acquired, has limited efficacy for others and is now a clear, sobering reality.   The upsetting truth: studies have also reported that depending on tumor characteristics and stage, 17 to 40% of patients treated with trastuzumab regiments for early-stage HER2+ BC go on to develop recurrences within 5 years.   Said another way, despite the fact that trastuzumab heralded a new era in the treatment of HER2+ BC, there remains a critical unmet medical need for preventing recurrence after treatment for early-stage HER2+ disease—and for preventing the approximately 6,000 to 8,000 deaths due to HER2+ metastatic disease every year in this country.  Accordingly, there also remains a need to expedite the development, study, and approval of safe, highly effective therapies for patients with high-risk early breast cancer.  And it is for this reason that the FDA released a draft guideline in May 2012 outlining an Accelerated Approval pathway for presurgical (neoadjuvant) treatments in breast cancer.

But why then the title above, “A Historic Moment”?  Last month, on Thursday, September 12th , the FDA convened its Oncologic Drugs Advisory Committee (ODAC), asking ODAC for the first time to consider Accelerated Approval for an oncologic agent in the neoadjuvant setting, based on a primary endpoint known as “pathologic complete response” (pCR).”  Pathologic complete response is proposed as a “surrogate endpoint” of tumor response that should be strongly correlated with more traditional endpoints, such as disease-free survival or overall survival.  In other words, if approved, this would be the first neoadjuvant regimen formally approved by the FDA for any type of cancer.

During this September 12th ODAC Panel, I had the privilege of serving as the Patient Representative as a temporary full voting member.  The question before the committee specifically concerned Accelerated Approval of the anti-HER2 therapy pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and docetaxel (Taxotere) for patients with HER2+ breast cancer in the neoadjuvant setting.   Like trastuzumab, pertuzumab is a monoclonal antibody that targets the HER2 receptor, yet it binds to a different part of the HER2 molecule and therefore does not compete with trastuzumab.   Pertuzumab prevents the pairing (called “dimerization”) of HER2 with other HER receptors (HER1, HER3, and HER4), serving to block the signaling pathways within the cell that lead to tumor growth.  When pertuzumab is combined with trastuzumab, it therefore provides a “dual” or more complete blockage of the HER pathway.

ODAC meeting at White Oak Campus

Approving an oncologic agent as a neoadjuvant therapy in early-stage disease would be historic since traditionally, new breast cancer drugs have first been approved in the setting of metastatic disease. Typically, approval for the treatment of early-stage BC then follows several years later based on the results of very large randomized postsurgical (adjuvant) trials with thousands of patients and prolonged follow-up.   If successful, neoadjuvant trials may therefore enable more rapid assessment of drug efficacy and expedite the approval of treatments for early breast cancer.

During this ODAC panel, the comprehensive discussion focused on several critical topics, including:

* the remaining unmet medical need for high-risk early HER2+ breast cancer and the far too many patients who have their cancer return as metastatic disease

* considerations regarding the use of pathologic complete response (pCR) as a primary endpoint in the neoadjuvant setting

* potential long-term toxicities associated with the neoadjuvant use of pertuzumab

* the need for very clear labeling to provide clear guidelines on proper patient selection (due to some data suggesting increased risk of cardiotoxicity) and the safest, most effective use of pertuzumab

*  the unique circumstances concerning pertuzumab, including its earlier approval as a first-line treatment for metastatic HER2+ BC based on statistically significant improvement in overall survival and its well-studied mechanism of action with the HER2 pathway and safety signals

* the need to consider the totality of the evidence concerning this agent

* the ongoing, now fully accrued APHINITY Phase III adjuvant trial that, if successful, could support conversion of accelerated approval to regular approval

On this last topic, many ODAC panel members stressed a critical point to the sponsor:  that if the results of the APHINITY adjuvant trial are in fact negative, Genentech should voluntarily remove the drug for the neoadjuvant treatment of early-stage breast cancer

During the public hearing portion of the session, many members of the public, including advocates, breast cancer survivors, and nonprofit advocacy organization leadership eloquently stressed the need for earlier, evidence-based treatment options and for treatments that may potentially prevent early high-risk HER2+ BC from later recurring, while also expressing the need for caution, urging Genentech to establish registries to follow those who receive pertuzumab specifically in the neoadjuvant setting for potential late toxicities.

Our panel ultimately voted 13-0 with one abstention in support of pertuzumab in combination with trastuzumab and doxetaxel for patients with HER2+ BC in the neoadjuvant setting.   And just a few weeks later, on September 30th, the FDA went on to approve pertuzumab in this setting, indeed making it the first FDA-approved pre-surgical breast cancer drug.

Perjeta (pertuzumab)

As stated by Dr. Mikkael Sekeres, ODAC Committee Chair, “This is a historic moment as we have voted to support the first approval of a drug for the neoadjuvant treatment of breast cancer: pertuzumab.  In doing so, we are supporting the rapid movement of a highly active drug for metastatic breast cancer to the first-line setting, with the hope that women with earlier stages of breast cancer will live longer and better.  We do this with some words of advice to Genentech.  All eyes will be on the confirmatory APHINITY trial and on you to verify this initial signal of efficacy and to confirm the bandwidth of safety that we have seen so far.  If these are not confirmed we urge you to avoid a repeat performance of Avastin and voluntarily remove this drug from the market.”

Upon announcing the approval of pertuzumab, Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in an FDA statement, “We are seeing a significant shift in the treatment paradigm for early stage breast cancer.  By making effective therapies available to high-risk patients in the earliest disease setting, we may delay or prevent cancer recurrences.’’

All eyes will indeed be on the large adjuvant APHINITY trial, with the hope that this was ultimately a critical first step in truly expediting the approval and availability of safe, highly effective treatments for patients with high-risk early BC and in significantly decreasing the risk of developing metastatic disease.

For patients with HER2+ breast cancer, whether newly diagnosed or long-term survivors, the HER2 Support Group provides information, resources, and support at http://her2support.org/.

The FDA’s Meeting Materials for the September 12, 2013 Meeting of the Oncologic Drugs Advisory Committee (ODAC) are available on the FDA’s website at http://tinyurl.com/bdsgot2

In addition, if you are interested in learning more about the FDA’s Patient Representative Program, visit http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/patientinvolvement/ucm123858.htm.

Please note: The views expressed on these pages are mine alone and do not represent those of any other party.

On Self-Advocacy and Paying It Forward

This week, I’ve had the privilege of contributing a Guest Blog column for Jessie Gruman’s important series on “What I Wish I’d Known Earlier About Cancer Survivorship.”

This is a topic that resonates with anyone who has received a cancer diagnosis, regardless of age, cancer type, or stage.  And as a five-time cancer survivor herself, Jessie thought it important to share the many lessons she learned over the years concerning the unique needs of those who have been diagnosed with and treated for cancer.

Jessie is President and Founder of the Center for Advancing Health (CFAH), a nonpartisan, Washington-based policy institute that is committed to increasing patients’ engagement in their own healthcare.  The CFAH actively engages with and listens to patients and translates what they learn into resources that help all of us participate fully in our own healthcare and that enable clinicians and policy makers to better understand and meaningfully support these patient-centered efforts.

The Center’s website and its blog, called the “Prepared Patient,” are valuable resources for patients, family members, clinicians, policy makers, and all those concerned about ensuring optimal, evidence-based healthcare. Appropriately, the  CFAH’s motto is “Evidence, Engagement, Equity.”  

These 3 “E’s” form much of the core of my advocacy efforts, so as soon as I began reading the resources on the Center’s site, I was hooked.  And then, when I read about the new series that Jessie was establishing for the Center’s blog–one that so openly and honestly shared the hard-won lessons many of us have learned as cancer survivors–I immediately found myself writing part of my story, where I took my initial steps toward self-advocacy and on the critical road toward paying it forward.

I’ve reposted my blog for the series here.  But I also encourage you to link directly to this posting on the Prepared Patient blog, so that you’ll have the opportunity to also read the many other blogs that have been written for this important series and to learn more about the Center’s resources.

“Advocacy: The Road We Decide to Walk on Today”

Debra Madden

Road toward advocacyThis post was contributed in response to Jessie Gruman’s What I Wish I’d Known Earlier about Cancer Survivorship series about the unique needs and responsibilities of people who have been diagnosed and treated for cancer.

The year was 1986. It was a cold, frosty day in December, and it had just become clear to me that my father simply couldn’t take it anymore. I was living with my parents, having graduated from college earlier that spring, and every morning, my father woke up to the sound of my coughing—coughing that had gotten progressively worse. I’d had a terrible cold shortly before my graduation that I just couldn’t seem to shake, so I attributed my coughing to that. But the fact was that for more than a year, I’d also been fighting terrible exhaustion, drenching night sweats, and, strangely enough, unbearable itching. I’d gone to a number of doctors, looking for some explanation, but none of them could seem to find anything wrong. They each assured me that it was probably “just stress.”  After all, I was soon graduating and was probably worried about finding a job, right? And as a young woman who otherwise seemed very healthy, what else could possibly be wrong? In fact, during my last doctor’s visit, I was actually led to feel embarrassed: why would I think there was something wrong if the doctors themselves couldn’t find anything? So I gave up and resigned myself to thinking that I was simply worn out from my last year of college and that I’d gradually begin to feel better.

But I didn’t get better: I simply got used to feeling pretty terrible and essentially ignored or repressed it, depending on the day. My “newest” symptom was the relentless coughing. Every morning like clockwork, I began to have a coughing attack that seemed to last a little bit longer than the one the day before. Then at breakfast each morning, my parents expressed their worry, and I repeated the fact that I’d been to doctor after doctor who couldn’t find anything wrong. Then, on that morning in December, I stepped out of the shower, started coughing — and couldn’t stop. I wasn’t able to catch my breath, I was gasping for air, and I was truly frightened.

As I made my way shakily to my bedroom, after ensuring that I was okay, my father asked me whether any of my doctors had ever taken a chest x-ray. When I shook my head, he told me firmly to call work and tell them that I wouldn’t be coming in today. He was bringing me to a doctor now, and in a tone that broached no argument, stated, “And we’re not leaving there until they give you a chest x-ray, a complete exam, and an explanation of what on earth is wrong.”

And when the doctor placed that x-ray on the light box, it was clear that I was in terrible trouble. My coughing and all the rest of my symptoms were due to stage 3 Hodgkin’s lymphoma.

So at the age of 22, my world changed.  When looking at that chest x-ray, I became a cancer survivor — and by their insistence that I receive that x-ray, my parents had already become my advocates. Yes, I had initially tried to get answers concerning my symptoms. But I was young, unworldly, and self-conscious and simply didn’t have the confidence to question my doctors. Unfortunately, I was much more apt to question myself, and that lack of persistence as much as anything resulted in stage 3 cancer at my diagnosis.

Fortunately, however, today I no longer question myself. I question my doctors. And if I hadn’t learned that very difficult lesson, I wouldn’t be here today writing this essay for you—because my Hodgkin’s diagnosis was just the beginning.

My cancer treatment took place in 1987 – 1988 and consisted of a very aggressive protocol, including eight cycles of chemotherapy (alternating MOPP/ABVD) followed by six weeks of high-dose radiation. In the years since, I developed what is now termed as numerous “late effects” due to my previous radiation. When I was in my 30s, more than 15 years after my initial treatment, I once again found myself in a role where I was “too young” to be exhibiting certain symptoms, but this time I had absolutely no reluctance in questioning any doctor’s “conventional wisdom.”

It began on a typical day where I worked as a transcriptionist at a local neurology practice. I was moving a few patient charts before leaving to go home. Although I wasn’t doing anything physically taxing and wasn’t feeling particularly stressed, I suddenly became unaccountably aware of my heart—it seemed to be racing. I could feel it pounding and almost galloping in my chest. I sat down for a few moments until the sensation stopped. When I was on my treadmill a day or so later, I involuntarily raised my left arm. It was then that I felt a heavy sensation in my chest. I got off the treadmill, and the feeling went away immediately. But when I laid down in bed a bit later, I inexplicably felt short of breath though I was obviously at rest. The next morning, I immediately called my PCP and explained my troubling symptoms. I was told they had an opening in a few weeks. It’s important to note that at that time, there wasn’t a great deal of discussion or understanding of late effects due to cancer treatment — that was to come a few years later. But a little voice in my head insisted, “Tell them about your radiation and chemotherapy now.”

This time, I didn’t question myself for a second. I cleared my throat, took a deep breath, and explained that I’d had radiation to the chest and chemotherapy with Adriamycin about 15 years before. I knew that what I was experiencing was not normal, and I was terrified that my heart had been damaged by my treatment. By advocating for myself, I was taken seriously, and I hung up with an appointment later that same day.

Surprisingly, my EKG results were normal. But I carefully outlined my history for the APRN who was examining me. I explained that although I was only in my 30s, I had serious concerns that my symptoms could be due to cardiotoxicity secondary to my radiation or chemotherapy. She agreed that heart disease was indeed rare in women my age, but that my history very much had to be taken into account. She thanked me for being so candid and specific about my previous medical history and the cancer treatments I’d had. She then explained that she wanted to make a few phone calls to have me seen emergently by a cardiologist.

The test results from my new cardiologist confirmed my fears: coronary artery fibrosis (scarring), stenosis (narrowing), and 90% blockage secondary to radiation.

My case was reviewed by a team of cardiologists due to the location of the blockage and the distinct risk of another coronary artery collapsing during an angioplasty. After conferencing, their overall recommendation was to conduct an angioplasty with stent placement. But they also stressed the need to have a team of cardiac surgeons on hand to perform a coronary artery bypass graft (CABG) should a second artery indeed collapse, leading to risk of a heart attack during the procedure. And it was 100% my choice: deciding to go with angioplasty or going directly to a CABG. It was one of the most agonizing decisions of my life. But I ultimately decided to go with the angioplasty—and a second artery did in fact collapse during the procedure. But the team was able to immediately do a second angioplasty for that artery and place a second stent. And thanks to my two cardiologists, the procedure was successful.

Years later, my APRN—the one who had listened to my story so carefully as I stepped into my role as a self-advocate for the first time—shared something with me that I’ll never forget.  She asked whether I remembered that she’d spent a great deal of time on the phone to ensure I was seen by a cardiologist emergently. I assured her that I recalled all too well. She told me that when she finally got a cardiologist on the phone, he listened to everything she outlined about my case, and his response was, “Why are you calling me about this patient?  She’s far too young for her symptoms to be caused by coronary artery disease.”  She told me that she then went over my case again, stressing my history of high-dose radiation to the chest area, my chemotherapy with Adriamycin (whose most dangerous side effect is heart damage), and why it was therefore so critical for me to be seen right away. He listened as she advocated for me, minutes after I’d finally advocated for myself.

And now, he too is an advocate: I was the first patient he’d seen with cardiotoxicity as a late effect of cancer treatment. Just months later, he emergently treated a young man who had also had Hodgkin’s lymphoma and developed the same cardiac symptoms I’d exhibited; he has given grand rounds on treatment-induced cardiotoxicity; he now advocates on the critical need for specialists, PCPs, and patients themselves to be aware of the potential for late effects of cancer treatment for all cancer survivors, no matter their age.

The words that author Catherine Ryan Hyde expressed in Chasing Windmills can be likened to the choices we make concerning self-advocacy and advocacy on the behalf of others:

“I keep telling you the future isn’t set in stone. It’s not all decided yet. The future is just what’s down the road we decided to walk on today. You can change roads anytime. And that changes where you end up.”

More Blog Posts by Debra Madden

Debra Madden lives is Newtown, Connecticut, and is a 2-time cancer survivor: Hodgkin’s lymphoma as a young adult and breast cancer 20 years later as a late effect of her original radiation treatment. She is an active cancer research advocate who serves on several national grant review committees and panels, including for the FDA, the Department of Defense Breast Cancer Research Program (BCRP) and the Patient-Centered Outcomes Research Institute (PCORI). You can read more of Ms. Madden’s blogs at Musings of a Cancer Research Advocate and find her on Twitter at @AdvocateDebM.

Ms. Madden’s photo is by Nancy Crevier at “The Newtown Bee.”