Pembrolizumab (Keytruda®, Merck) has received accelerated FDA approval for patients with metastatic small cell lung cancer (SCLC) experiencing disease progression during or after platinum-based chemotherapy following at least one other previous line of therapy.
Metastatic SCLC, or extensive-stage SCLC, comprises around 15% of all lung cancers and occurs primarily in heavy smokers. It carries a dismal outlook; only 5% of patients with extensive-stage SCLC live for two years after diagnosis.
Approval was based on data from SCLC cohorts in two multicenter, non-randomized, open-label trials involving patients with multiple tumor types, KEYNOTE-158 (NCT02628067) Cohort G and KEYNOTE-028 (NCT02054806) Cohort C1. These two cohorts together consisted of 83 patients with SCLC experiencing disease progression on or after at least two previous lines of therapy. For KEYNOTE-028, participants were required to have programmed death-ligand 1 (PD-L1) expression.
"This study is, to our knowledge, the first report to evaluate the immune checkpoint inhibitor pembrolizumab in patients with heavily pretreated (87.5% with two or more lines of prior therapy; 37.5% with three or more) extensive-stage SCLC," write the authors of the KEYNOTE-028 study, led by Patrick A. Ott, MD, PhD, Clinical Director of the Center for Immuno-Oncology at Dana-Farber Cancer Institute, in their publication in the Journal of Clinical Oncology. "Pembrolizumab showed clinically meaningful antitumor activity and overall was well tolerated; the safety was consistent with the reported safety profile in other tumor types."
Patients with SCLC in both trials received intravenous pembrolizumab, with 64 patients receiving 200 mg every three weeks and 19 patients receiving 10 mg/kg every two weeks for a maximum of 24 months or until disease progression or unacceptable toxicity. The trial's primary end points were overall response rate and duration of response.
Pembrolizumab produced an overall response rate of 19%, with a complete response rate of 2%. For the 16 patients who responded to pembrolizumab, the medication produced responses lasting at least six months in 94% of patients, lasting at least twelve months in 63%, and lasting at least 18 months in 56%.
Adverse reactions experienced by at least 20% of patients included fatigue, decreased appetite, cough, nausea, and constipation. Nine percent of patients discontinued treatment due to adverse reactions, and 25% had at least one dose withheld as a result of adverse reactions. Thirty-one percent of patients experienced adverse reactions of grade 3 or higher, with the most frequent being pneumonia and pleural effusion, both of which occurred in at least 2% of patients.
The recommended dose is 200 mg administered intravenously over 30 minutes every three weeks for up to 24 months or until disease progression or unacceptable toxicity.
For More Information
Ott PA, Elez E, Hiret S, et al (2017). Pembrolizumab in patients with extensive-stage small-cell lung cancer: results from the phase Ib KEYNOTE-028 study. J Clin Oncol, 35(34):3823-3829. DOI:10.1200/JCO.2017.72.5069Image credit: Yale Rosen. Licensed under CC BY-SA 2.0