Abstract
Results from a phase Ib study indicate that pembrolizumab is well tolerated by patients with advanced triple-negative breast cancer, and yields durable responses. This provides proof-of-principle that a refractory subtype of breast cancer may be targetable by immunotherapy, potentially adding to the disease's limited treatment options.
With no approved targeted agents for triple-negative breast cancer (TNBC), women diagnosed with this disease have few treatment options besides chemotherapy. However, the immune checkpoint inhibitor pembrolizumab (Keytruda; Merck) may be effective in some patients, according to a report from the 2014 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX, December 9–13.
By binding to the PD-1 receptor and blocking its ligands, PD-L1 and PD-L2, pembrolizumab—approved by the FDA in September for advanced melanoma—prevents tumor cells from using this pathway to escape immune surveillance.
In the phase Ib study presented at SABCS, 18.5% of 27 evaluable patients responded to pembrolizumab, “an encouraging signal that's worthy of further evaluation,” said principal investigator Rita Nanda, MD, associate director of the Breast Medical Oncology program at the University of Chicago. All participants had advanced TNBC and were PD-L1–positive; most had previously received and progressed on multiple lines of therapy. One patient achieved a complete response to pembrolizumab, four had partial responses, and seven saw their disease stabilize.
Rita Nanda, MD, presents findings of a study on the use of pembrolizumab for the treatment of triple-negative breast cancer at the San Antonio Breast Cancer Symposium.
Rita Nanda, MD, presents findings of a study on the use of pembrolizumab for the treatment of triple-negative breast cancer at the San Antonio Breast Cancer Symposium.
The median progression-free survival was just under 2 months. Three patients remained on pembrolizumab for at least 11 months, which “speaks to the response durability,” Nanda said. Although one patient died of treatment-related disseminated intravascular coagulation, pembrolizumab's main side effects—including low-grade joint and muscle pain, fatigue, and nausea—were largely well-tolerated, Nanda added.
Oncologists are optimistic about the use of pembrolizumab for TNBC, an aggressive, difficult-to-treat disease. “When it comes to harnessing the immune system in breast cancer, we've just started scratching the surface,” said Jennifer Litton, MD, director of the Breast Medical Oncology Education program at The MD Anderson Cancer Center in Houston, TX. “This disease, intrinsically, is not like melanoma and other cancers that have higher immune infiltrates.”
Edith Perez, MD, deputy director at large for the Mayo Clinic Cancer Center, agreed. “Breast cancer has not typically been considered targetable with immunotherapy,” she said, “so it's gratifying to have proof-of-principle data showing a glimpse of [pembrolizumab] activity in patients with refractory disease.”
Nanda noted that “the degree of PD-L1 positivity and response [to pembrolizumab] didn't appear to correlate, so PD-L1 alone may not be the most appropriate biomarker.” Research is under way to investigate the relationship between outcome and PD-L2 expression, and a phase II trial to further evaluate pembrolizumab in TNBC will begin enrolling patients in the first half of 2015.
“This was a small study,” said Eric Winer, MD, director of Dana-Farber Cancer Institute's Breast Oncology Center in Boston, MA, “but the fact that a handful of patients responded durably to pembrolizumab is a signal saying, ‘Look into this further,’ which is where the next study, and the one after that, should go.“
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