On October 16, 2023, the FDA approved a new indication for pembrolizumab (Keytruda; Merck), a PD-1 inhibitor, combined 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).
Pembrolizumab monotherapy was previously approved for the adjuvant treatment of patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC, after resection and platinum-based chemotherapy as first-line treatment, as well as in patients with NSCLC and PD-L1 expression without ALK or EGFR mutations, and for patients with metastatic NSCLC and PD-L1 expression, after platinum-based chemotherapy. Pembrolizumab also has indications for the treatment of several other cancer types.
This approval of pembrolizumab was supported by results of the KEYNOTE-671 study, a multicenter, randomized, double-blind, placebo-controlled clinical trial of 797 patients with previously untreated and resectable stage II, IIIA, or IIIB (N2) NSCLC by the American Joint Committee on Cancer’s Cancer Staging Manual, 8th Edition. Patients were randomized to pembrolizumab or to placebo, with platinum-based chemotherapy, every 3 weeks for 4 cycles (neoadjuvant treatment) followed by continued single-agent pembrolizumab or placebo every 3 weeks for up to 13 cycles (adjuvant treatment).
The primary efficacy measures were overall survival (OS) and investigator-assessed event-free survival (EFS). The median OS was not reached for patients who received pembrolizumab (95% confidence interval [CI], not estimable-not estimable) and was 52.4 months for patients who received placebo (95% CI, 45.7-not estimable; hazard ratio [HR], 0.72 [95% CI, 0.56-0.93]; P=.0103). The median EFS was not reached in the pembrolizumab arm (95% CI, 34.1-not estimable) and was 17 months in the placebo arm (95% CI, 14.3-22; HR, 0.58 [95% CI, 0.46-0.72]; P<.0001).
The most common (≥20%) adverse events with pembrolizumab treatment in KEYNOTE-671 were nausea, fatigue, neutropenia, anemia, constipation, decreased appetite, a decrease in white blood cell count, musculoskeletal pain, rash, cough, vomiting, diarrhea, and dyspnea. Among patients who received neoadjuvant pembrolizumab, 6% were unable to undergo surgery as a result of adverse reactions compared with 4.3% in the placebo arm. Among patients who received neoadjuvant treatment and surgery in the pembrolizumab arm, 3.1% had delays in surgery as a result of adverse reactions compared with 2.5% in the placebo arm.
The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks. Pembrolizumab should be administered before chemotherapy when both treatments are administered on the same day.