Immunotherapy Slows TNBC Progression

An investigational immunotherapy that blocks the interaction between two proteins that inactivate the immune system is showing promise for treating triple-negative breast cancer (TNBC), according to preliminary results from a phase I trial announced at the American Association for Cancer Research Annual Meeting 2015, held in Philadelphia, PA, April 18–22.

The trial is evaluating the experimental monoclonal antibody MPDL3280A (Genentech) in a variety of advanced solid tumors. MPDL3280A blocks the binding of PD-L1, expressed on many cancer and immune cells, to the PD-1 receptor. Interaction between the two proteins interferes with the ability of T cells to mount an immune response.

The trial enrolled 54 patients with previously treated metastatic TNBC, 21 of whom had PD-L1–positive disease, defined as having PD-L1 on 5% or more of immune cells that infiltrate the tumor. Among those 21 patients, there was a 24-week progression-free survival rate of 27% and an objective response rate of 19% after treatment with MPDL3280A, said Leisha Emens, MD, PhD, a member of the Cancer Immunology and Breast and Ovarian Cancer Programs at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, MD, at a news conference. After 56 weeks, the median duration of response had not yet been reached.

“Importantly, these responses [in the PD-L1–positive group] included two complete responses and two partial responses, and three of the four responses were ongoing at the time of data cutoff,” said Emens. “Moreover, there were three patients who appeared to experience a phenomenon known as pseudoprogression, which is an atypical response pattern seen in some patients treated with this class of agents.”

The patients who experienced pseudoprogression showed durable shrinkage of their target lesions while developing new lesions at other sites, explained Emens. However, the patients remained clinically well and eventually showed regression of the secondary lesions, suggesting that the emergence of other lesions does not necessarily call for an immediate change in therapy, she said.

TNBC, for which chemotherapy is the only approved treatment option, may be particularly susceptible to immunotherapy, said Emens. It has a higher mutation rate and a higher number of tumor-infiltrating lymphocytes relative to other breast cancer subtypes, both of which help boost the immune response. Emens noted that greater numbers of tumor-infiltrating lymphocytes have been associated with better clinical outcomes in patients with TNBC.

Based on the promising results, Genentech's parent company, Roche Holding AG, announced last week that it plans to proceed directly to a phase III trial for MPDL3280A later this year. The FDA has already designated the drug as a Breakthrough Therapy for PD-L1–positive advanced non–small cell lung cancer and metastatic bladder cancer.

“Further evaluation of MPDL3280A is ongoing in this study in both PD-L1–expressing and PD-L1–nonexpressing patients,” said Emens. “We are now preparing to launch a global randomized trial testing MPDL3280A in combination with Abraxane (nab-paclitaxel; Celgene) as first-line therapy for patients with metastatic triple-negative breast cancer.”

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