The FDA has approved pembrolizumab for treatment of patients with metastatic non-small cell lung cancer whose tumors express PD-L1 with disease progression during or following treatment with a platinum-based agent. (See Figure.)
The study included 550 advanced lung cancer patients, 61 of whom had the genetic mutation and already been treated with chemotherapy. In 41% of patients, tumors shrank after treatment with the drug, an effect that lasted between 2.1 and 9.1 months.
“The approval of this drug and a test to identify patients most likely to benefit has the potential to transform the way that lung cancer is treated,” Dr. Edward Garon, a researcher at the University of California Los Angeles, told NBC News. “For people battling this deadly disease, this approach provides real hope of long-lasting responses while avoiding the toxicities of typical chemotherapy.”
Many Promising Results
At the 2015 European Cancer Congress, impressive findings from a phase II study were presented for pembrolizumab in patients with Merkel cell carcinoma. “In the study, the objective response rate with pembrolizumab was 71%, which included a complete response in 2 of 14 patients,” according to a report on OncLive. The responses appeared to be durable, according to lead investigator Paul Nghiem, MD, PhD.
In September 2014, the FDA approved pembrolizumab for treatment of patients with advanced or unresectable melanoma who are no longer responding to other drugs.
Results of studies of pembrolizumab in patients with advanced NSCLC, melanoma, gastric cancer, urothelial cancer, and head and neck carcinoma, presented during the ESMO 2014 Congress in Madrid, showed promising activity and tolerability from this then novel monoclonal antibody.
Mechanism: Programmed Death Blockade
Pembrolizumab is able to achieve a blockade of both programmed death ligand 1 and 2 (PD-L1 and L2). It has demonstrated clinical activity in multiple tumor types while showing no cytotoxic effects. Evidence suggests maximum efficacy with dosing every 2 to 3 weeks.
PD-1 is a negative co-stimulatory receptor expressed primarily on activated T cells. Binding of PD-1 to its ligands inhibits effector T-cell function. Expression of PD-L1 on tumor cells and macrophages can suppress immune surveillance and permit neoplastic growth.
The Literature
PubMed returns more than 140 results in a search for pembrolizumab.
