In this issue:
By Beverly Canin, BCAction Board Member
The 2012 ASCO Annual Meeting drew more than 31,000 attendees from 117 countries, including over 300 patient advocates representing approximately 100 advocacy organizations. In a poll of the 25,500 professional attendees, 25% of the respondents indicated breast cancer was a primary area of interest. Though the question allowed for more than one response, only 4% indicated a primary interest in cancer prevention/epidemiology, 4% in patient and survivor care and 2% in ethics. These numbers were striking to me.
ASCO prides itself on its educational programs to improve patient care, its frequently updated clinical practice guidelines, its informational booklets and fact sheets for patients, and its disease- specific symposia. Obviously, physicians are trained to treat patients and most are clearly looking for ways to improve their practices, but one still has to wonder—I certainly did—at such an apparent disconnect between professional interests and the issues that are so vitally important to patients.
Of the hundreds of presentations in workshops, plenary and poster sessions at ASCO, there are always headline grabbers – the ‘breakthroughs’ as the media likes to call them. The most publicized results from this meeting was the EMILIA study, which show the efficacy of T-DM1, a monoclonal anti-body conjugate, in patients with HER2-positive locally advanced or metastatic breast cancer, though the progression free survival gain is modest and no overall survival gain is indicated.
Childhood chest radiation and breast cancer risk
Other headline research related to breast cancer included findings that chest radiation in childhood for Hodgkin’s Lymphoma increases breast cancer risk in adults. A federal study which is tracking survivors of childhood cancers indicates that by age 50, these survivors have a breast cancer incidence rate of about 30 percent, about the same as women who carry a BRCA1 or BRCA2 mutation, which suggests they should undergo the same surveillance as the BRCA1/2 carriers.
Abraxane and Ixempra for metastatic breast cancer
Dr. Hope Rugo, director of breast oncology and clinical trials education at the University of California, San Francisco reported on a large Phase III clinical trial which showed that certain newer, more expensive drugs were no better and even more toxic than a cheaper, older drug, paclitaxel, that is used in patients with locally advanced or metastatic breast cancer. Median progression free survival was 10.6 months for those taking paclitaxel, compared with 9.2 months for Abraxane and 7.6 months for Ixempra.
Cymbalta for chemo-induced numbness and tingling
Another Phase III clinical trial by the Cancer and Leukemia Group B (CALGB) showed that Cymbalta, which is used to treat depression, anxiety, and the pain caused by diabetes-related neuropathy, appears to reduce the numbness and tingling associated with taxane or platinum-based chemotherapy. The study found that 33 percent of the patients taking Cymbalta reported a 30 percent or greater reduction in pain scores compared with 17 percent of those on a placebo, with a daily 30mg dose not as effective as a daily 60mg dose.
“Overdiagnosis” Dilemma: Prescription for Change”
One very compelling presentation which did not make the news was “Addressing the “Overdiagnosis” Dilemma: Prescription for Change”, by Laura Esserman, MD. Dr. Esserman is boldly challenging the current paradigm which identifies and treats Ductal Carcinoma in Situ (DCIS) as cancer with prescriptions for lumpectomies, mastectomies and radiation. She calls for a new paradigm which recognizes the heterogeneity of lesions, acknowledges that the biology of lesions trumps size in determining progression, uses known facts to help distinguish indolent, low grade DCIS from high grade and introduces risk-based screening protocols. She recommends that low-grade DCIS be re-named and treated as atypia, which it closely resembles. She stressed the need for more clinical trials to determine treatment approaches, indicating that there is one underway for intermediate grade lesions and one being planned for high grade lestions. Dr. Esserman said in situ disease detection has increased 500%. She insists that cancer, not DCIS, should be the target of screening.
Genomic sequencing for cancer
Another take-away from the meeting is how genomic sequencing has impacted the way cancer is viewed, treated and researched. The entire genetic sequence of a cancer can now be analyzed and targeted therapies administered that weren’t possible a few years ago. Genetic analysis has allowed the identification of cancer subtypes and revealed the heterogeneity of cancers – even within the same tumor. Treatments can now be targeted for the biology of the tumor rather than the site, with potentially far fewer side effects. But there are some big questions that accompany this progress:
- Can the increasing cost to society of genetic research and targeted treatment be sustained?
- Will insurance companies support it so that everyone will be able to benefit or will it be reserved for the few who can afford it?
- Is this research leading toward prevention or just ‘chronic disease’ maintenance?
It’s essential that we consider these questions as we move forward.
“Designing Clinical Trials for the Elderly: A Road to What?”
On a final note, because of work I do as an advocate with the Cancer and Aging Research Group, I was asked to present the advocate perspective in an Educational Session on Designing Clinical Trials for the Elderly. I added the question “A Road to What?” to my title, not with an expectation to answer the question, but with a hope to leave it indelibly in the minds of the researchers as they design clinical trials for the elderly and other populations.
I pointed out that the scientific jargon is “translational research”, but advocates and patients simply want to know: “How is this research going to help me or my children and their children?” We advocates think my participation was quite a coup because, as far as anyone knows, this is the first time an advocate has presented as faculty at the ASCO Annual Meeting.
I let the audience know that my talk was informed by my years of experience as a breast cancer advocate interacting with patients and survivors of all ages, advocates in other cancers as well as breast cancer, clinicians and researchers in a variety of settings. I explored some of the following questions:
- Why have an advocate perspective?
- What do we mean by advocate?
- What do we mean by “elderly”?
- How does this diverse population view clinical trials?
- Why the skepticism and suspicion?
- Can we overcome the skepticism?
- What questions do the “elderly” want asked in clinical trials?
- Biomedical or behavioral – does it make a difference?
- What do we “elderly” need from researchers and clinicians?
- How do researchers find and work with advocates and advocate organizations?
I received many compliments about my presentation. The most rewarding comments came from two post doctoral students who thanked me enthusiastically, saying how much they appreciated hearing what I presented because they don’t learn anything like it in their courses.
By BCAction Staff
Breast Cancer Action has been a leading voice for breast cancer patients at the Food & Drug Administration (FDA) for over twenty years. As the watchdog of the breast cancer movement we insist that any new treatment approved by the FDA is shown to extend life, improve quality of life or cost less than drugs currently on the market. We urgently need more effective, less toxic treatments that benefit women, not only Big Pharma’s bottom line.
The recent treatment news we cover below addresses HER2-positive breast cancer, which accounts for less than a third of breast cancer diagnoses.
Get more treatment news in our report-back from this year’s ASCO Annual Meeting.
T-DM1 was in the headlines after Genentech released results of their Phase III clinical trial of T-DM1 at the annual ASCO conference in June, and announced their plans to seek FDA approval for the drug. The focus of the media frenzy was only partly on the results of the study, showing slight improvement in progression-free survival of just over three months in women with HER2+ metastatic breast cancer. The primary media excitement was about the science behind the creation of this new targeted treatment.
T-DM1 enables targeted delivery of the chemotherapy DM1 to HER2+ cancer cells by linking it to the antibody trastuzumab. We believe the significance of this “breakthrough”—if it is that—is in the science of creating the antibody-drug conjugate.
Breast Cancer Action has been following T-DM1 for a number of years and remains focused on real demonstrated benefit to patients, not media hype. In 2010, we successfully advocated for the FDA to deny accelerated approval of T-DM1 for metastatic breast cancer because Genentech’s data at that time relied on a Phase II trial that did not give sufficient information on the drug’s efficacy and safety.
With the recent release of the Phase III data, we have some new evidence to consider in evaluating our position on T-DM1 when it comes before the FDA. We do not believe progression free survival is an adequate substitute for overall survival and the T-DM1 data on overall survival is not yet mature, although it has been suggested that there appears to be a benefit. We remember the early elation in 1998 when Trastuzumab (Herceptin) was approved by the FDA. It was heralded as a new era in treating metastatic breast cancer. What we have learned in the years since is that cancer cells are incredibly adaptable and eventually some women develop drug resistance to trastuzumab. The current Phase III studies on T-DM1 do not give any long term indication on whether the effects of T-DM1 will last or whether cancer cells will eventually adapt to this treatment as well. We hope this type of targeted treatment can ‘outsmart’ the cancer cells for the long-term but it’s just too soon to know, nor celebrate, what is only an incremental improvement compared to current therapy.
However, in evaluating new drugs and their benefit to women, we also consider cost—which is unknown at this time but certainly not expected to be less than other treatments—and side effects. While there are still a large number of women experiencing severe side effects (grade 3 or worse) the percentage is smaller than with standard chemo (41% compared to 57% on standard chemo). In addition, the nature of the side effects is quite different, with patients on the pertuzumab arm spared the rash, vomiting/nausea and hair loss of standard chemo.
Based on these new Phase III data, T-DM1 appears to meet BCAction’s absolute minimum criteria for approving a new treatment as it seems the drug can offer patients a slight improvement in quality of life. We will watch for when T-DM1 goes before the FDA and ask that OS be part of the follow-up required if this drug gets accelerated approval.
While we are the first to champion the need for improved quality of life for women living with breast cancer, the media uproar about this drug — inspired by an additional 3.2 months of progression-free survival — is a sobering reminder of how desperately we need significantly better treatment options for women diagnosed with breast cancer, particularly women with metastatic disease.
On June 8, the Food and Drug Administration approved the use of pertuzumab (under the brand name Perjeta) for use in combination with trastuzumab (Herceptin) and the chemotherapy docetaxel for the treatment of patients with HER2+ metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Subsequently, following the FDA approved Perjeta, Genentech announced in a press release there is indication that the drug is showing improvement in overall survival. However, Genentech won’t release the actual data until it is presented at medical conferences later this year and we have not been able to review the company’s claims.
At the San Antonio Breast Cancer Synposium in December 2011, the data released from the CLEOPATRA trial showed that combining Herceptin with pertuzumab delayed progression of tumor growth by six additional months, with the greatest benefit for ER- tumors. The study examined the effect of combining pertuzumab and trastuzumab in a double-blind randomized study for HER2+ metastatic breast cancer in women who were previously untreated for the metastasis. These results were widely heralded by clinicians as among the most important findings presented at the conference.
However, Breast Cancer Action has not yet seen data that demonstrates it meets our drug approval guidelines. The CLEOPATRA trial focuses on progression-free survival (PFS) rather than focusing on overall survival (OS). Additionally, the drug is more toxic with more side effects. While the researchers claim “significantly prolonged progression-free survival, with no increase in cardiac toxic effects,” the rates of febrile neutropenia and diarrhea of grade 3 or above were higher in the pertuzumab group than in the control group. It is also important to note that these rates of toxicity in both groups, and particularly the pertuzumab-treated group, were even higher in the Asian patients that participated in the study. The majority of patients in the study were white or Asian, with insubstantial representation of other racial and ethnic groups.
In addition to overall survival and quality of life data, Breast Cancer Action considers cost, recognizing that drugs that cost less than current treatments get into the hands of more women. Initial information regarding cost has indicated that a course of treatment with pertuzumab and trastuzumab could cost approximately $200,000. A price tag this high inevitably limits availability especially to already underserved communities.
Of particular concern to us is the fact that this drug was approved by the FDA without going through the typical process of review through the Oncologic Drug Advisory Committee (ODAC). Although not all cancer drugs are required to go through this process, most do–especially drugs that have questionable end-points and toxic effects. We are concerned that the FDA has given Genentech a pass on the normal review process given the lack of clear OS information, the higher rates of febrile neutropenia—particularly in the Asian subgroup—and no data on other minority populations. BCAction is concerned about this short-changing of the FDA on review of pertuzumab. Because of pertuzumab’s failure to meet our criteria for approval, BCAction will outline our concerns to the FDA and vigorously monitor follow-up on the drug.
Upcoming FDA drug reviews include Tykerb, (lapatinib) scheduled to be reviewed by the FDA in late July. GlaxoSmithKline is seeking FDA approval of Tykerb tablets for use in combination with Herceptin for patients with Her2+ metastatic breast cancer that has progressed after previous treatment with Herceptin.
Tykerb is currently approved for use in Her2+ breast cancer in specific situations. In 2007, Tykerb was approved with the chemotherapy capecitabine for Her2+ breast cancer for women in whom the cancer has progressed following chemotherapy and Herceptin. In January 2010 Tykerb received accelerated approval for treatment in combination with hormonal therapy of postmenopausal “triple positive” (ER+/PR+/Her2+) metastatic breast cancer for women in whom the cancer has progressed after previous treatment of chemotherapy and Herceptin. Common side effects of Tykerb include diarrhea, fatigue, nausea, and rashes and the drug has been linked to toxic hepatitis.
We will take a close look at the evidence on Tykerb as it becomes available to the public. Based on our patient-centered analysis of the data, we are prepared to testify at the ODAC hearing to ensure that patient interest is represented at the FDA.