Pembrolizumab Approved for Neoadjuvant/Adjuvant Treatment of Non–Small Cell Lung Cancer

Lung cancer x-ray.

The FDA has approved pembrolizumab (Keytruda®, Merck) for non–small cell lung cancer (NSCLC) as neoadjuvant treatment in combination with platinum-containing chemotherapy, and with continuation of single-agent pembrolizumab as post-surgical adjuvant treatment for resectable tumors, defined as those with a tumor ≥4 cm or node-positive.  

Why it matters: “In patients with NSCLC, pembrolizumab has shown efficacy as monotherapy in the adjuvant and advanced settings and in combination with chemotherapy in metastatic disease,” wrote Heather A. Wakelee, MD, Professor of Oncology at Stanford Health Care, and colleagues, in their abstract of KEYNOTE-671 (NCT03425643), on which the approval was based, presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting. “KEYNOTE-671 evaluated the addition of pembrolizumab to platinum-based chemotherapy as neoadjuvant therapy followed by resection and pembrolizumab versus placebo as adjuvant therapy in patients with early-stage NSCLC.”

What they studied: Efficacy was evaluated in the phase 3, multicenter, double-blind, placebo-controlled KEYNOTE-671 trial, which enrolled 797 patients with previously untreated and resectable stage II, IIIA, or IIIB NSCLC according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition. Patients were randomized 1:1 to receive 200 mg pembrolizumab or placebo in combination with platinum-based chemotherapy as neoadjuvant treatment every three weeks. After completing four cycles and undergoing surgical resection, patients continued single-agent pembrolizumab or placebo as adjuvant treatment, every three weeks for up to 13 cycles.

The primary end points were overall survival and investigator-assessed event-free survival, with secondary end points of major pathologic response and pathological complete response.

What they found: Median overall survival and median event-free survival were not reached in the pembrolizumab plus platinum chemotherapy arm, compared with 52.4 months and 17.0 months in the placebo plus platinum chemotherapy arm, respectively. The difference in median overall survival was not statistically significant. The pembrolizumab group also saw an improvement in major pathologic response compared with placebo (30.2% vs 11.0%) and pathological complete response (18.1% vs 4.0%).

Adverse events: The most common adverse events experienced by ≥20% of patients receiving pembrolizumab plus platinum chemotherapy were nausea, fatigue, neutropenia, anemia, constipation, decreased appetite, decreased white blood cell count, musculoskeletal pain, rash, cough, vomiting, diarrhea, and dyspnea. Among patients who received neoadjuvant therapy, 6% of those in the pembrolizumab arm were unable to receive surgery due to adverse events, compared with 4.3% of those in the placebo arm. Of patients who received both neoadjuvant treatment and surgery, 3.1% of those in the pembrolizumab arm had delays in surgery due to adverse events, compared with 2.5% of those in the placebo arm. Additional safety details from the neoadjuvant and adjuvant phases are outlined in the prescribing information for pembrolizumab.

What’s next: Later analyses will determine if overall survival is significantly different between groups. Future study will attempt to determine the relative contributions of the neoadjuvant and adjuvant components of the regimen.

Conclusion: “Pembrolizumab plus chemotherapy followed by resection and adjuvant pembrolizumab provided a statistically significant and clinically meaningful improvement in event-free survival, pathological complete response, and major pathologic response in patients with resectable stage II, IIIA, and IIIB NSCLC,” concluded Dr. Wakelee and colleagues.

Instructions: The recommended dose of pembrolizumab is 200 mg every three weeks or 400 mg every six weeks. When given on the same day, pembrolizumab should be administered prior to chemotherapy.

For More Information

Wakelee HA, Liberman M, Kato T, et al (2023). Perioperative pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med, 389:491-503. DOI:10.1056/NEJMoa2302983

Wakelee HA, Liberman M, Kato T, et al (2023). KEYNOTE-671: randomized, double-blind, phase 3 study of pembrolizumab or placebo plus platinum-based chemotherapy followed by resection and pembrolizumab or placebo for early stage NSCLC. J Clin Oncol (ASCO Annual Meeting Abstracts), 41(suppl_17). LBA100. DOI:10.1200/JCO.2023.41.17_suppl.LBA100 (2023). Efficacy and safety of pembrolizumab (MK-3475) with platinum doublet chemotherapy as neoadjuvant/adjuvant therapy for participants with resectable stage II, stage IIA, and resectable IIIB (T3-4N2) non–small cell lung cancer (MK-3475-671/KEYNOTE-671). NLM identifier: NCT03425643.

Keytruda® (pembrolizumab) prescribing information (2023). Merck. Available at:

US Food & Drug Administration (2023). FDA approves neoadjuvant/adjuvant pembrolizumab for resectable non–small cell lung cancer. Available at:

Image credit: James Heilman. Licensed under CC BY-SA 4.0 DEED

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