On January 26, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage IB (T2a, ≥ 4 cm), II, or IIIA non–small cell lung cancer (NSCLC).
KEYNOTE-091
Efficacy was evaluated in KEYNOTE-091 (ClinicalTrials.gov identifier NCT02504372), a multicenter, randomized, triple-blind, placebo-controlled trial. Patients had not received neoadjuvant radiotherapy or chemotherapy. They were randomly assigned 1:1 to receive pembrolizumab at 200 mg or placebo intravenously every 3 weeks for up to 1 year.
Stratification factors included receipt of adjuvant chemotherapy and region of the world. Of the 1,177 patients who were randomly assigned, 1,010 (86%) received adjuvant platinum-based chemotherapy following complete resection.
The major efficacy outcome measure was investigator-assessed disease-free survival. The trial met its primary endpoint, demonstrating a statistically significant improvement in disease-free survival in the overall population. In an exploratory subgroup analysis of the 167 patients who did not receive adjuvant chemotherapy, the disease-free survival hazard ratio was 1.25 (95% confidence interval [CI] = 0.76–2.05). For patients who received adjuvant chemotherapy, the median disease-free survival was 58.7 months in the pembrolizumab arm (95% CI = 39.2 months to not reached) and 34.9 months in the placebo arm (95% CI = 28.6 months to not reached; hazard ratio = 0.73; 95% CI = 0.60–0.89).
The adverse reactions observed in KEYNOTE-091 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 adverse reactions of myocarditis occurred.
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
