On October 16, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) with platinum-containing chemotherapy as neoadjuvant treatment, and with continuation of single-agent pembrolizumab as postsurgical adjuvant treatment, for resectable (tumors ≥ 4 cm or node-positive) non–small cell lung cancer (NSCLC).
KEYNOTE-671
Efficacy was evaluated in KEYNOTE-671 (ClinicalTrials.gov identifier NCT03425643), a multicenter, randomized, double-blind, placebo-controlled trial in 797 patients with previously untreated and resectable stage II, IIIA, or IIIB (N2) NSCLC per the American Joint Committee on Cancer 8th edition. Patients were randomly assigned 1:1 to receive either pembrolizumab or placebo, with platinum-based chemotherapy, every 3 weeks for 4 cycles (neoadjuvant treatment) followed by either continued single-agent pembrolizumab or placebo every 3 weeks for up to 13 cycles (adjuvant treatment).
The major efficacy outcome measures were overall survival and investigator-assessed event-free survival. Median overall survival was not reached in the pembrolizumab arm (95% confidence interval [CI] = not estimable to not estimable) and 52.4 months for those receiving placebo (95% CI = 45.7 months to not estimable; hazard ratio [HR] = 0.72, 95% CI = 0.56–0.93, P = .0103). Median event-free survival was not reached in the pembrolizumab arm (95% CI = 34.1 months to not estimable) and 17 months in the placebo arm (95% CI = 14.3–22.0 months; HR = 0.58, 95% CI = 0.46–0.72, P < .0001).
In KEYNOTE-671, the most common adverse reactions reported in at least 20% of patients were nausea, fatigue, neutropenia, anemia, constipation, decreased appetite, decreased white blood cell count, musculoskeletal pain, rash, cough, vomiting, diarrhea, and dyspnea. Of the patients who received neoadjuvant treatment in the pembrolizumab arm, 6% were unable to receive surgery because of adverse reactions compared with 4.3% in the placebo arm. In addition, 3.1% of patients who received neoadjuvant treatment and surgery in the pembrolizumab arm had delays in surgery from adverse reactions compared with 2.5% in the placebo arm.
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks. Pembrolizumab should be administered prior to chemotherapy when given on the same day.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
