FDA approves neoadjuvant/ adjuvant pembrolizumab for resectable non-small cell lung cancer

Regulatory approval: On Oct 16, 2023, the FDA approved pembrolizumab (Keytruda) with platinum-containing chemotherapy as neoadjuvant therapy, followed by continuation of single-agent pembrolizumab as adjuvant therapy after surgery, for resectable NSCLC (tumors ≥4 cm or node positive). The decision was based on KEYNOTE-671, which showed improvements in OS and investigator-assessed EFS versus placebo plus chemotherapy using the same perioperative approach.

FDA approval (Oct 16, 2023): perioperative pembrolizumab for resectable NSCLC

The FDA granted a regulatory approval on 2023-10-16 for pembrolizumab (Keytruda, Merck) in combination with platinum-containing chemotherapy as neoadjuvant treatment, with continued single-agent pembrolizumab as post-surgical adjuvant treatment for resectable NSCLC (tumors ≥4 cm or node positive).

Supporting trial: KEYNOTE-671 (NCT03425643)

  • Design: multicenter, randomized, double-blind, placebo-controlled
  • Population: 797 patients with previously untreated, resectable Stage II, IIIA, or IIIB (N2) NSCLC (AJCC 8th edition)
  • Regimen: pembrolizumab or placebo q3w for 4 cycles with platinum-based chemotherapy (neoadjuvant), then pembrolizumab or placebo q3w up to 13 cycles (adjuvant)
  • Primary efficacy endpoints: overall survival (OS) and investigator-assessed event-free survival (EFS)

Efficacy results

  • OS: median not reached (95% CI: NE, NE) with pembrolizumab vs 52.4 months (95% CI: 45.7, NE) with placebo; HR 0.72 (95% CI: 0.56, 0.93); p=0.0103
  • EFS: median not reached (95% CI: 34.1, NE) vs 17 months (95% CI: 14.3, 22.0); HR 0.58 (95% CI: 0.46, 0.72); p<0.0001

Safety highlights

Common adverse reactions (≥20%) included nausea, fatigue, neutropenia, anemia, constipation, decreased appetite, decreased WBC count, musculoskeletal pain, rash, cough, vomiting, diarrhea, and dyspnea. In the pembrolizumab arm, 6% did not undergo surgery due to adverse reactions (vs 4.3% placebo); surgical delays occurred in 3.1% (vs 2.5%).

Dosing per FDA communication

Recommended pembrolizumab dose: 200 mg q3w or 400 mg q6w; administer pembrolizumab prior to chemotherapy when given the same day.

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