The FDA has approved pembrolizumab (Keytruda®, Merck) for adjuvant treatment of stage IB, II, or IIIA non–small cell lung cancer (NSCLC), following resection and platinum-based chemotherapy.
"Although adjuvant chemotherapy improves overall survival in completely resected NSCLC, the absolute 5-year survival benefit is moderate compared with observation alone," wrote Mary O'Brien, MD, Head of Royal Marsden Hospital's Lung Unit, and colleagues, in their published results of the KEYNOTE-091 trial (NCT02504372), on which approval was based. "Until recently, efforts to improve the efficacy of platinum-based chemotherapy in the adjuvant setting were unsuccessful. . .we compared pembrolizumab with placebo as adjuvant therapy for completely resected stage IB– IIIA NSCLC."
Safety and efficacy were evaluated in the phase 3, triple-blind, multicenter trial, in which 1,177 patients were randomized 1:1 to receive either 200 mg of pembrolizumab or placebo via intravenous infusion every three weeks for up to one year. Out of the total population, 1,010 of the patients received adjuvant platinum-based chemotherapy following complete resection. The remaining 167 patients who did not receive platinum-based chemotherapy were studied as an exploratory subgroup.
The primary end point measured was investigator-assessed disease-free survival. Median disease-free survival in those receiving platinum-based chemotherapy and pembrolizumab was at 58.7 months, compared with 34.9 months for those receiving platinum-based chemotherapy and placebo. In the exploratory subgroup of 167 patients not receiving platinum-based chemotherapy, the disease-free survival hazard ratio was 1.25.
The most common adverse events experienced by patients in the trial were similar to those experienced by other patients receiving pembrolizumab as a single agent for treatment of NSCLC, with the exceptions of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). In addition, two fatal adverse events of myocarditis occurred.
"Pembrolizumab significantly improved disease-free survival compared with placebo and was not associated with new safety signals in completely resected, PD-L1-unselected, stage IB-IIIA NSCLC," concluded Dr. O'Brien and colleagues. "Pembrolizumab is potentially a new treatment option for stage IB-IIIA NSCLC after complete resection and, when recommended, adjuvant chemotherapy, regardless of programmed death ligand 1 (PD-L1) expression."
The recommended dosage is 200 mg of pembrolizumab every three weeks, or 400 mg every six weeks, for up to 12 months or until disease recurrence or unacceptable toxicity.
For More Information
O'Brien M, Paz-Ares L, Marreaud S, et al (2022). Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol, 23(10):1274-1286. DOI:10.1016/S1470-2045(22)00518-6
Clinicaltrials.gov (2020). Study of pembrolizumab (MK-3475) vs placebo for participants with non–small cell lung cancer after resection with or without standard adjuvant therapy (MK-3475-091/KEYNOTE-091) (PEARLS). NLM identifier: NCT02504372.
Keytruda® (pembrolizumab) prescribing information (2023). Merck. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125514s128lbl.pdf
US Food and Drug Administration (2023). FDA approves pembrolizumab as adjuvant treatment for non–small cell lung cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-non-small-cell-lung-cancer
Image credit: Yale Rosen. Licensed under CC BY-SA 2.0
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