ASCO 2015: Experimental Immunotherapy Shows High Response Rate in Advanced Lung Cancer
An early-phase study testing the anti–PD-L1 agent MPDL3280A in combination with standard chemotherapy in the treatment of advanced non–small cell lung cancer (NSCLC) has provided promising early results, prompting multiple phase III studies in lung cancer. The findings are being presented at the 2015 ASCO Annual Meeting (Abstract 8030).
Study Details
In this phase Ib study, patients with untreated NSCLC received one of three standard platinum-based chemotherapy regimens (paclitaxel/carboplatin, pemetrexed [Alimta]/carboplatin, or nab-paclitaxel [Abraxane]/carboplatin) with MPDL3280A, an antibody targeting PD-L1. Early results from the first 37 patients showed impressive response rates of between 60% to 75%, comparing favorably with historical outcomes with chemotherapy alone, where historical response rates from randomized trials are around 30% to 35%. In addition, two complete responses have been documented, with no evidence of lung cancer or computed tomography scans.
“A complete response is not typically seen in patients with stage IV lung cancer,” said the abstract's lead author, Stephen V. Liu, MD, Assistant Professor of Medicine at Georgetown Lombardi Comprehensive Cancer Center. “And the response rates seen with MPDL3280A and chemotherapy were higher than one would expect with chemotherapy alone.”
Researchers say the combination therapy was well tolerated by patients, with no unexpected toxicities. The most frequently reported adverse events were linked to use of chemotherapy, investigators reported, including nausea, fatigue, and constipation. Side effects associated with MPDL3280A use included anemia, low levels of neutrophils, and low platelet counts.
Anti–PD-1 and Anti–PD-L1 Antibodies
Anti–PD-L1 and anti–PD-1 antibodies are designed to enhance the activity of T cells. “The body needs to tightly regulate immune function,” Dr. Liu explained. “When T cells are activated under normal conditions, they are quickly suppressed, to prevent overactivation. This suppression is controlled by the interaction of PD-1 and PD-L1, the protein that binds to the PD-1 receptor.”
“The problem is that many tumors express PD-L1 and are able to escape T-cell immunity,” Dr. Liu continued. “So these drugs are designed to keep the immune signal on.”
The U.S. Food and Drug Administration has approved two anti–PD-1 antibodies for the treatment of refractory melanoma and one anti–PD-1 antibody for the treatment of refractory squamous cell lung cancer. “MPDL3280A represents an approach at targeting not PD-1, but its ligand, PD-L1, which may provide some advantages. The combination with chemotherapy in the first-line setting certainly deserves further study,” Dr. Liu concluded.
The study was supported by Genentech. Dr. Liu serves on the advisory board for Genentech.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
