MPDL3280A Shows Activity in Triple-Negative Breast Cancer

April 20, 2015

In an ongoing study, the immunotherapy MPDL3280A continues to be well-tolerated and to show signs of activity in triple-negative breast cancer patients.

In an updated analysis of a cohort of metastatic triple-negative breast cancer patients, it was demonstrated that MPDL3280A, a programmed death ligand 1 (PD-L1)–targeted immunotherapy, continues to be well-tolerated and to show signs of activity.

The 24-week progression-free survival (PFS) rate was 27% and the objective response rate was 19%. Three of the four patients who responded to treatment are continuing to respond.

Three patients had partial responses and two patients had complete responses. The duration of responses so far ranged from 0.1 to more than 41.6 weeks, and the median response time has not yet been reached.

These results, part of an ongoing phase I clinical trial, were presented by Leisha A. Emens, MD, PhD, an associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, at the American Association for Cancer Research (AACR) Annual Meeting, held April 18 to 22 in Philadelphia.

Preliminary results of this patient cohort were presented in December 2014 at the San Antonio Breast Cancer Symposium (SABCS).

MPDL3280A is a monoclonal antibody targeting PD-L1. The interaction between programmed death 1 (PD-1) and PD-L1 prevents T cells from attacking tumor cells. Inhibiting this interaction with MPDL3280A reinstates the ability of T cells to efficiently attack tumor cells.

According to Emens and her study coauthors, triple-negative breast cancer patients are candidates for immunotherapy because this tumor type has an increased number of tumor-infiltrating lymphocytes (TILs), higher PD-L1 tumor expression levels, and a high mutation rate that can produce neoantigens inducing immune responses, as compared with other breast cancer subtypes.

The trial enrolled a cohort of 54 triple-negative breast cancer patients-with both PD-L1–positive and PD-L1–negative tumors. Previous studies in other tumor types, including melanoma, have shown that not all cancer patients express PD-L1 on their tumor cells and that a lack of PD-L1 expression, thus far, has not precluded patients from responding to treatment with either PD-L1– or PD-1–directed antibodies.

The most common adverse events were loss of appetite, nausea, fatigue, and fever. Of the 54 patients that were evaluated for side effects, 63% had at least one drug-related adverse event and 11% had at least one grade 3 event. Grade 3 events included adrenal insufficiency, neutropenia, nausea, vomiting, and decreased white blood cell count. A single patient with an atrial septal defect had a grade 5 adverse event of pulmonary hypertension. “The safety data are consistent with this drug class across tumor types,” Emens told Cancer Network.

Patients had a median age of 48 years, with ages ranging from 29 to 82 years. They were heavily pretreated, with 85% having had at least four prior treatments, including those in the neoadjuvant and adjuvant settings. Fifty-nine percent of patients had visceral metastases and 11% had bone metastases.

Another immune checkpoint antibody, pembrolizumab, directed against PD-1, is also currently being investigated in triple-negative breast cancer.