On October 16, 2023, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda®) 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).

FDA update

Efficacy was evaluated in KEYNOTE-671 (NCT03425643), a multicenter, randomized, double-blind, placebo-controlled trial in 797 patients with previously untreated and resectable stage II, IIIA, or IIIB (N2) NSCLC by the American Joint Committee on Cancer’s Eighth Edition Cancer Staging Manual. Patients were randomized 1:1 to receive either pembrolizumab or placebo, with platinum-based chemotherapy, every three weeks for four cycles (neoadjuvant treatment) followed by either continued single-agent pembrolizumab or placebo, every three weeks for up to 13 cycles (adjuvant treatment). Refer to the prescribing information for chemotherapy details and surgical window.

The major efficacy outcome measures were overall survival (OS) and investigator-assessed event-free survival (EFS). Median OS was not reached in the pembrolizumab arm (95% CI = not estimable [NE], NE) and 52.4 months for those receiving placebo (95% CI = 45.7, NE; HR = 0.72; 95% CI = 0.56, 0.93; p = 0.0103). Median EFS was not reached in the pembrolizumab arm (95% CI = 34.1 months, NE) and 17 months in the placebo arm (95% CI = 14.3, 22.0; HR = 0.58; 95% CI = 0.46, 0.72; p < 0.0001).

The most common adverse reactions reported in at least 20% of patients in the clinical trial were nausea, fatigue, neutropenia, anemia, constipation, decreased appetite, decreased white blood cell counts, musculoskeletal pain, rash, cough, vomiting, diarrhea, and dyspnea. Of the patients who received neoadjuvant treatment, 6% in the pembrolizumab arm and 4.3% in the placebo arm were unable to receive surgery because of adverse reactions. In addition, 3.1% of patients in the pembrolizumab arm and 2.5% in the placebo arm who received neoadjuvant treatment and surgery had delays in surgery because of adverse reactions. Refer to the prescribing information for detailed safety descriptions of the neoadjuvant and adjuvant phases.

The recommended pembrolizumab dose is 200 mg every three weeks or 400 mg every six weeks. Administer pembrolizumab prior to chemotherapy when administered on the same day.

View the full prescribing information for pembrolizumab.

This review used Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Office of Oncology Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.