1. Cohen, Elly PhD

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As I expect is true of most people who are told they have breast cancer, I experienced a rollercoaster of emotions throughout my diagnosis and treatment in 1998-but due to the many courageous and generous women before me who participated in adjuvant therapy clinical trials, my ride came to a safe and rather soft landing. Twenty years earlier, my mother was also told she had early stage breast cancer, but without adjuvant hormone or chemotherapy, her ride came to an early end a mere 4 years after her diagnosis.

clinical trials. cli... - Click to enlarge in new windowclinical trials. clinical trials (BCT), which I helped found, underscores my appreciation for how clinical trials made such a difference between my mother's death and my own survival. Our mission at BCT is to make patient consideration of trials the norm, rather than the exception. Our approach is to raise awareness and access to clinical trials, not only to improve individual patient lives, but also for the collective benefit of the greater breast cancer community.


Advancing Breast Cancer Care

Oncology clinical trials are constantly evolving to improve care. Even my mother, for whom the efficacy of adjuvant therapy had not yet been demonstrated, benefitted from a trial that spared her the disfigurement of radical mastectomy. Today, based on advances in breast cancer care, the 5-year survival rate of patients with localized disease is 99 percent. But for patients with metastatic breast cancer, the 5-year survival is only 26 percent. Clinical trials for metastatic breast cancer have recently given rise to new therapies, which while not curative, have been shown to prolong survival.


Consider patients with HER2+ breast cancer. Once an indication of poor survival, patients with metastatic HER2+ tumors now have at their disposal several therapeutic weapons that target the HER2 receptor, including a chemotherapy-loaded smart bomb. Clinical trials have also increased options for metastatic ER+ cancer including CDK 4/6 and mTOR inhibitors for first- and second-line therapy.


In addition to these recent graduates to standard of care, new targeted agents for HER2+ and ER+ metastatic are being studied in clinical trials every day. While targeted therapy for metastatic triple negative breast cancer lags behind that for HER2+ and ER+ disease, the relative immunogenic properties of these tumors have led to clinical trials of pembrolizumab and atezolizumab for triple negative breast cancer, two immunotherapeutic agents which have recently been approved for treatment of non-small cell lung cancer. New agents are also being tested in clinical trials for patients with brain metastases. These include agents that have demonstrated activity in crossing the blood-brain barrier such as tucatinib (ONT-380) and etirinotecan pegol.


Breast cancer patients also have the opportunity to participate in clinical trials with novel designs that can potentially accelerate the pace of research. The I-SPY trial, for example, is enrolling patients with locally advanced breast cancer who are at high risk of recurrence. It is evaluating investigational neoadjuvant therapies using an adaptive design that continuously learns from prior patient cohorts to more accurately randomize newly enrolled patients.


Basket trials, a new design for precision medicine, are another option for breast cancer patients, for whom standard care is no longer an option. Basket trials enrolling breast cancer patients including NCI-MATCH and TAPUR, enroll patients based on their tumor mutation status rather than primary site of cancer. NCI-MATCH features investigational therapies in 24 treatment arms, whereas TAPUR is looking at approved therapies in off-label scenarios in 15 treatment arms. In both cases, breast cancer patients who have a targeted mutation are placed in the same treatment arm with patients from other cancers with the same genetic abnormality.


Why Aren't More Patients Participating?

It is puzzling, given the potential benefits of trials to one's own outcomes and that of the community, that the rate of trial participation remains well below 10 percent. Misinformation about trials remain a documented barrier to participation. Here are some of the most troublesome misperceptions:


* Patient fear of not receiving treatment: Many patients incorrectly think the term "placebo-controlled" means the possibility of being randomized to a treatment arm that includes only a sugar pill. The truth is that in all phase III randomized trials both the control and experimental groups receive standard of care. For the experimental group, the standard of care is coupled with the investigational agent, whereas for the control group the standard of care is coupled with a placebo. The only time a control group would receive no treatment is if there is no standard of care available as was the case with the study of tamoxifen for chemoprevention, where the standard of care at the time was watchful waiting.


* Patient fear of being a "guinea pig": Some patients fear they will receive an experimental agent that will be harmful. While clinical trials are research and thereby inherently carry risk, patients need to be assured about ways trials are designed to minimize risk. These include extensive preclinical testing and the slow, deliberate pace of clinical trials that continuously evaluates safety at every juncture, starting with phase I trials, where safety is the main objective. Unless safety is proven in phase I, the trial cannot continue to phase II. Moreover, patients should be made aware that it is their right to withdraw from a study for any reason at any time. This is a standard part of informed consent, but patients need to know this before they are being actively considered for a trial.


* Lack of awareness about trials: Another factor that precludes consideration of trials is patients' misunderstanding of the diversity of trials. In addition to treatment trials for those who have run out of standard care options, there are also treatment trials for patients who have been newly diagnosed with early stage disease or those who are at various points along their metastatic journey. In addition, patients should be made aware of non-treatment trials that focus on symptom management and quality of life. Patients should also be encouraged to participate in long-term observational studies such as the Cancer Experience Registry, the Metastatic Breast Cancer Project, and the Health of Women Study. Data collected in these registries are used to generate hypotheses for future clinical trials.



How Can Patients & Providers Find Trials?

While is the most complete registry of clinical trials taking place in the U.S., its technical language and descriptions of trials can pose as a barrier for many patients. BCT is a nonprofit, patient-friendly alternative to that was developed specifically to help patients learn about and find trials in a trusted, consumer-friendly setting. Launched in 2008, its goal is to engage patients to consider trials and talk about them with their providers during routine decision-making at the point-of-care. BCT maintains a registry of over 600 trials, which can be searched in two ways:


1. BCT Match-the cornerstone of BCT, this service provides personalized matching to trials based on a user's self-reported diagnostic and treatment history. As a feature of BCT Match, users can subscribe to its Trial Alert Service for a weekly email notification of newly listed trials for which they may be eligible. BCT Match was validated in a research pilot co-sponsored by the UCSF Carol Franc Buck Breast Care Center and the NCI, prior to its launch in 2008.


2. BCT Browse-as an alternative to trial matching, BCT Browse provides easy access to the BCT trial registry via searchable keywords or links to "QuickView" categories of trials organized by trial type (e.g., immunotherapy) or tumor type (e.g., inflammatory breast cancer).



BCT trial summaries are written in patient-friendly language. This includes highlighting each study's rationale, research objectives, study plan, and convenience factors, including travel distance to the nearest research site and contact information for participating research sites. In 2016, BCT logged over 130,000 visitor sessions. It operates as a program of QuantumLeap Healthcare Collaborative, a nonprofit organization affiliated with UCSF.


Metastatic Trial Search (MTS) is a new clinical trial search engine designed specifically for patients with metastatic breast cancer and powered by BCT. Launched in collaboration with five breast cancer advocacy organizations, on whose website it is embedded, MTS provides easy access to trial information from within a patient's trusted community. In January 2017, MTS expanded to 13 sites providing an important service to metastatic patients who are most likely to benefit from clinical trials.


Every advance in breast cancer care results from a clinical trial, the timely completion of which relies upon a collaboration among patients, providers, and the research community. By increasing patient awareness and access to clinical trials, and Metastatic Trial Search encourage patients to talk with their providers about opportunities for trial participation. In a climate where consideration of trials is the norm instead of the exception, investigational agents that are safe, effective, and can positively impact patient outcomes can move from the laboratory to the clinic in a significantly more accelerated and efficient way.


ELLY COHEN, PHD, is Program Director with

Elly Cohen, PhD. Ell... - Click to enlarge in new windowElly Cohen, PhD. Elly Cohen, PhD