Pembrolizumab Receives FDA Approval Before and After Lung Cancer Surgery

On October 16, 2023, the US Food and Drug Administration (FDA) approved, for patients with resectable non–small-cell lung cancer (tumor diameter ≥4 cm or node-positive), the immunotherapy pembrolizumab (Keytruda) with platinum-containing chemotherapy as neoadjuvant (preoperative) treatment, followed after surgery by adjuvant (supportive) single-agent treatment.

FDA Approval Based on the KEYNOTE-671 Study

The efficacy of perioperative pembrolizumab was evaluated in KEYNOTE-671, a phase-3, multicenter, randomized, double-blind, placebo-controlled trial involving 797 previously untreated patients with resectable stage II, IIIA, or IIIB (N2) non–small-cell lung cancer (NSCLC).

Patients received platinum-based chemotherapy with either pembrolizumab or placebo every 3 weeks for 4 cycles (the neoadjuvant phase). They then underwent surgery. Afterward, patients continued either pembrolizumab alone or placebo every 3 weeks for up to 13 cycles (the adjuvant phase).

Results

The main efficacy outcomes were overall survival (OS) and investigator-assessed event-free survival (EFS).

• Pembrolizumab as perioperative (neoadjuvant + adjuvant) treatment reduced the risk of cancer progression, recurrence, or death by 42%.
• Median overall survival was not reached in the pembrolizumab arm (95% CI: not estimable [NE], NE), compared with 52.4 months with placebo (95% CI: 45.7, NE) (hazard ratio [HR] 0.72 [95% CI: 0.56, 0.93]; p-value=0.0103).
• Median EFS was not reached in the pembrolizumab arm (95% CI: 34.1 months, NE) and was 17 months in the placebo arm (95% CI: 14.3, 22.0) (HR 0.58 [95% CI: 0.46, 0.72]; p-value=<0.0001).

In KEYNOTE-671, reported in more than 20% of patients, the most common adverse reactions were nausea, fatigue, neutropenia, anemia, constipation, decreased appetite, decreased white blood cell count, musculoskeletal pain, rash, cough, vomiting, diarrhea, and shortness of breath. Among patients receiving neoadjuvant treatment, 6% in the pembrolizumab arm could not undergo surgery because of adverse reactions, compared with 4.3% in the placebo arm. Among patients receiving neoadjuvant treatment and surgery, adverse reactions also delayed surgery in 3.1% in the pembrolizumab arm versus 2.5% in the placebo arm.

The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks. When given on the same day, administer pembrolizumab before chemotherapy.