FDA approves Pembrolizumab for resectable NSCLC in both neoadjuvant and adjuvant setting

By Dr. Kanak Parmer

Texas Tech University Health Sciences Center

On October 16,2023 the U.S. Food and Drug Administration approved pembrolizumab for patients with resectable non-small cell lung cancer (NSCLC) tumors ≥4 cm or node positive.

Study ID number: NCT03425643

Approval was based on the KEYNOTE-671, a phase 3, multicenter, double-blind, placebo-controlled trial with 797 patients with previously untreated and resectable stage II, IIIA, or IIIB (N2) NSCLC. Patients were either given Pembrolizumab with platinum-based chemotherapy or just platinum based-chemotherapy every 3 weeks for 4 cycles as neoadjuvant treatment, followed by continued single-agent pembrolizumab or placebo every 3 weeks for up to 13 cycles as adjuvant treatment.

The primary outcome measures were overall survival (OS) and event-free survival (EFS) and the median follow-up was 25.2 months. EFS at 2 years was 62.4% in the pembrolizumab group and 40.6% in the placebo group (HR 0.58; 95% CI, 0.46-0.72; P<0.001). The estimated 2-year OS was 80.9% in the pembrolizumab group and 77.6% in the placebo group but did not reach statistical significance. There were significant improvements in secondary endpoints-major pathologic response rate and pathologic complete response.

The most common adverse reactions reported in ≥ 20% of patients were nausea, fatigue, neutropenia, anemia, constipation, decreased appetite, white blood cell count decreased, musculoskeletal pain, rash, cough, vomiting, diarrhea and dyspnea. Treatment-related AEs led to discontinuation of treatment for 12.6% versus 5.3% in  pembrolizumab and placebo arm respectively.

Among patients with resectable, early-stage NSCLC, neoadjuvant pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab significantly improved event-free survival, major pathological response, and pathological complete response as compared with neoadjuvant chemotherapy alone followed by surgery.