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.
