On October 16, 2023, pembrolizumab was approved for use with platinum-containing chemotherapy as neoadjuvant treatment and as single-agent adjuvant treatment in patients with resectable (tumors ≥ 4 cm or node-positive) non–small cell lung cancer (NSCLC).¹

Supporting Efficacy Data

Approval was based on findings in the double-blind multicenter KEYNOTE-671 trial (ClinicalTrials.gov identifier NCT03425643). In this study, 797 patients with previously untreated and resectable stage II, IIIA, or IIIB (N2) NSCLC were randomly assigned to receive neoadjuvant pembrolizumab at 200 mg or placebo plus platinum-based chemotherapy (cisplatin at 75 mg/m² and either pemetrexed at 500 mg/m² on day 1 or gemcitabine at 1,000 mg/m² on days 1 and 8) every 3 weeks for 4 cycles followed within 4 to 12 weeks after surgery by adjuvant single-agent pembrolizumab at 200 mg or placebo every 3 weeks for up to 13 cycles.

Median overall survival was not reached (95% confidence interval [CI] = not estimable to not estimable) in the pembrolizumab group vs 52.4 months (95% CI = 45.7 months to not estimable) in the placebo group (hazard ratio [HR] = 0.72, 95% CI = 0.56–0.93, P = .0103). Median event-free survival was not reached (95% CI = 34.1 months to not estimable) in the pembrolizumab group vs 17 months (95% CI = 14.3–22.0 months) in the placebo group (HR = 0.58, 95% CI = 0.46–0.72, P < .0001).

How It Is Used

The recommended dose is 200 mg every 3 weeks or 400 mg every 6 weeks. Neoadjuvant treatment in combination with chemotherapy is given for 12 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity; pembrolizumab should be administered prior to chemotherapy when given on the same day. Adjuvant single-agent treatment is continued for 39 weeks after surgery or until recurrence or unacceptable toxicity.

Safety Profile

In KEYNOTE-671, the most common adverse events of any grade reported in at least 20% of patients in the pembrolizumab group were nausea, fatigue, neutropenia, anemia, constipation, decreased appetite, decreased white blood cell count, musculoskeletal pain, rash, cough, vomiting, diarrhea, and dyspnea.

During neoadjuvant treatment with chemotherapy, serious adverse events occurred in 34% of patients, most commonly pneumonia (4.8%), venous thromboembolism (3.3%), and anemia (2%). Adverse events led to discontinuation of any drug in 18%, most commonly acute kidney injury (1.8%) and interstitial lung disease. Fatal adverse events occurred in 1.3% of patients, including unknown cause (0.8%), sepsis (0.3%), and immune-mediated lung disease (0.3%). Adverse events prevented surgery in 6% of the pembrolizumab group vs 4.3% of the placebo group and delayed surgery in 3.1% vs 2.5%.

Among 290 patients who received adjuvant pembrolizumab, serious adverse events occurred in 14%, most commonly pneumonia (3.4%). Adverse events led to discontinuation of treatment in 12%, most commonly diarrhea (1.7%) and interstitial lung disease (1.4%). One fatal adverse event was reported (pulmonary hemorrhage).

Pembrolizumab has warnings or precautions for immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic reactions, and solid organ transplant rejection; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving pembrolizumab. 

REFERENCE

1. Keytruda (pembrolizumab) injection, for intravenous use, prescribing information, Merck & Co, Inc, October 2023. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125514s139lbl.pdf. Accessed November 2, 2023.