The second most common cause of skin cancer death, Merkel cell carcinoma (MCC) is a rare and lethal cancer that usually metastasizes quickly. Researchers have discovered that the immunotherapy drug pembrolizumab (Keytruda®), which has already been FDA approved as a second-line treatment for MCC, elicits a better response rate and increased progression-free survival compared with chemotherapy as a first-line treatment for this condition.
In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), published in the Journal of Clinical Oncology, 50 treatment-naive adults with advanced MCC received 2 mg per kg of body weight of pembrolizumab every three weeks for up to two years. Sixty four percent of participants had Merkel cell polyomavirus-positive tumors.
The response rate to pembrolizumab was 56%, with 24% of participants experiencing a complete response. Pembrolizumab produced a response rate of 59% in patients with polyomavirus-positive tumors and a response rate of 53% in polyomavirus-negative tumors. At two years after the first dose of pembrolizumab, the progression-free survival rate was 48.3%, and the overall survival rate was 68.7%.
"This is the earliest trial of immunotherapy as a front-line therapy for Merkel cell carcinoma, and it was shown to be more effective than what would be expected from traditional therapies, like chemotherapy," remarked one of the study authors, Suzanne L. Topalian, MD, Associate Director and Professor of Surgery at the Bloomberg~Kimmel Institute for Cancer Immunotherapy. "Immunotherapy provides an effective treatment for patients with Merkel cell carcinoma who before had few options. Immunotherapy is unique in cancer treatment, because it does not directly target cancer cells but rather removes constraints on the immune system's natural ability to find and destroy cancer cells."
Pembrolizumab is effective in treating MCC because it acts as a checkpoint inhibitor and blocks programmed cell death protein 1 (PD-1), a protein found on the surface of a type of immune cell called T cells. When PD-1 binds to PD-L1, another protein critical to the immune system, T cells are blocked from killing cancer cells. As a result of pembrolizumab's ability to block PD-1, T cells are able to kill cancer cells.
"Under the microscope, PD-L1 looks like an armor around the cancer cells," commented another study author, Janis M. Taube, MD, Director of the Division of Dermatopathology and Associate Professor of Oncology at Johns Hopkins University. "Pembrolizumab interrupts PD-1 signaling by blocking the communication between PD-1 and PD-L1, removing the stop signal, and re-engaging the immune system to go after cancer cells."
These findings set a strong foundation for further research concerning immunotherapy as first-line treatment for cancer.
For More Information
Nghiem P, Bhatia S, Lipson EJ, et al (2019). Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy. J Clin Oncol. [Epub ahead of print] DOI:10.1200/JCO.18.01896
Image courtesy of Nephron