At the 33rd Annual Miami Breast Cancer Conference (March 10-11, 2016; Miami Beach, FL), presenters called for new ways to evaluate the success of novel agents for the treatment of breast cancer.
Although overall survival (OS) may have once been considered the “gold standard” outcome measure in oncology, Maurie Markman, MD, national director for Medical Oncology, Cancer Treatment Centers of America, said in his presentation that continuing to look at OS as the primary endpoint in studies requiring hundreds of patients slows the approval process and denies patients access to drugs from which they could benefit.
Dr Markman used imatinib as an example. In phase 3 randomized trials, imatinib was never shown to improve OS when used as a frontline therapy for chronic myeloid leukemia because it was being compared with another drug, interferon. However, when used as a second line therapy after interferon had failed, it was found to be very successful despite the fact that OS was not improved.
As alternatives, Dr. Markman suggested that the industry begin to look at endpoints such as response rate of long duration and time to disease progression, and that they evaluate patient outcomes in comparison with a robust historical database. Additionally, personalized approaches to drug evaluation could include comparing time to disease progression for an individual patient after he or she has received treatment with a novel agent with the time to progression for that same patient while on a previous regimen.
“We need some way to aggressively, realistically, and rapidly demonstrate utility of these agents so we can decide whether or not we want to bring them into our armamentarium for the benefit of our patients,” concluded Dr. Markman.
In another presentation, Gunter von Minckwitz, MD, PhD, German Breast Cancer Group, University of Frankfurt (Frankfurt, Germany), said that pathologic complete response (pCR) may still have a role in accelerated neoadjuvant approvals for select patients with early stage breast cancer, despite the fact that it remains an unproven surrogate endpoint.
The use of pCR as an endpoint for drug approvals can provide earlier access to promising new compounds, Dr von Minckwitz asserted. To illustrate his point, he used the example of pertuzumab, which gained approval based on pCR as a surrogate endpoint in 2013. Because of this approval, patients with HER2-positive locally advanced, inflammatory or early-stage breast cancer had access to pertuzumab—a highly effective treatment—3 to 4 years earlier than they otherwise would have.
Dr von Minckwitz noted that, although using pCR as an endpoint can expedite approvals, it is not meant to support a full indication by the US Food and Drug Administration. Also, some subsequent studies have failed to show a connection between improvements in pCR and survival, causing some to question its utility. More research is already underway testing the effectiveness of pCR as it relates to survival and quality of life to determine whether it can be used in the approval of other neoadjuvant therapies for breast cancer.
