On January 26, 2023, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda®) for adjuvant treatment following resection and platinum-based chemotherapy of patients with stage IB (T2a ≥ 4 cm), II, or IIIA non-small cell lung cancer (NSCLC).

FDA Approves Pembrolizumab as Adjuvant Treatment for Non-Small Cell Lung Cancer

Efficacy was evaluated in KEYNOTE-091 (NCT02504372), a multicenter, randomized, triple-blind, placebo-controlled trial. Patients had not received neoadjuvant radiotherapy or chemotherapy. Patients were randomized (1:1) to receive pembrolizumab 200 mg or placebo via IV every three weeks for up to one year. Stratification factors included receipt of adjuvant chemotherapy and region of the world. Of the 1,177 patients randomized, 1,010 (86%) received adjuvant platinum-based chemotherapy following complete resection.

The major efficacy outcome measure was investigator-assessed disease-free survival (DFS). The trial met its primary endpoint, demonstrating a statistically significant improvement in DFS in the overall population. In an exploratory subgroup analysis of the 167 patients who did not receive adjuvant chemotherapy, the DFS hazard ratio was 1.25 (95% CI = 0.76, 2.05). Among patients who received adjuvant chemotherapy, median DFS was 58.7 months in the pembrolizumab arm (95% CI = 39.2, not reached) and 34.9 months in the placebo arm (95% CI = 28.6, not reached) (hazard ratio = 0.73; 95% CI = 0.60, 0.89).

The adverse reactions observed in patients in the trial were generally similar to those occurring in other patients with NSCLC receiving pembrolizumab as a single agent with the exception of hypothyroidism (22%), hyperthyroidism (11%), and pneumonitis (7%). Two fatal myocarditis reactions occurred in patients treated with pembrolizumab.

The recommended dose of pembrolizumab is 200 mg every three weeks or 400 mg every six weeks for up to 12 months or until patients experience disease recurrence or unacceptable toxicity.

View the full prescribing information for pembrolizumab.

The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate the 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 investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.