Adjuvant Pembrolizumab Gets FDA Approval in NSCLC

The FDA has approved pembrolizumab (Keytruda) for the adjuvant treatment of patients with completely resected stage IB (T2a ≥ 4 cm diameter), II, or IIIA non–small cell lung cancer (NSCLC) following platinum-based chemotherapy. The approval is based on data from the KEYNOTE-091 trial (NCT02504372).¹

Findings from the trial showed that treatment with pembrolizumab (n = 580) reduced the risk of disease symptom development by 27% compared with placebo (n = 581). The median disease-free survival (DFS) was 58.7 months (95% CI, 39.2-not reached [NR]) vs 34.9 months (95% CI, 28.6-NR) for pembrolizumab vs placebo, respectively (HR, 0.73; 95% CI, 0.60-0.89).¹

The label comes with a warning for immune-mediated pneumonitis, which was reported in 41 patients (7%) treated with pembrolizumab in KEYNOTE-091 with 26 patients discontinuing treatment. Events were fatal (0.2%), grade 4 (0.3%), and grade 3 (1%) in nature. Patients who developed symptoms were treated with high-dose corticosteroids for a median duration of 10 days (range, 1 day to 2.3 months). Dose interruptions were reported for 54% of patients receiving pembrolizumab, 63% discontinued treatment, and 71% resolved symptoms.²

The label notes that other adverse events (AEs) observed in KEYNOTE-091 were consistent with previously reported data for patients with NSCLC receiving pembrolizumab. However, rates of hypothyroidism were higher at 22%.² Additional AEs of note in the study were hyperthyroidism (11%), and pneumonitis (7%) with pembrolizumab.²

KEYNOTE-091 enrolled patients with stage IB/II-IIIA NSCLC who have undergone complete resection of either lobectomy or pneumonectomy with or without adjuvant chemotherapy. Individuals were randomly assigned to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for up to 1 year. The primary outcome was DFS with secondary end points of overall survival and lung cancer specific survival.³

The median age of patients who received adjuvant treatment following resection and chemotherapy was 64 years (range, 35-84), and 49% were 65 years or older. Among the overall populations 68% were men, 77% were White, 18% were Asian, and 86% were current or former smokers.²

In terms of disease stage, 11% of patients had stage IB, 57% had stage II, and 31% had stage IIIA disease. Tumor proportion score (TPS) was reported as follows: 39% had PD-L1 TPS lower than 1%; 33% had TPS 1% to 49%, and 28% had TPS at least 50%.²

The median duration of exposure to pembrolizumab was 11.7 months with 68% of patients in the pembrolizumab arm exposed to the agent for at least 6 months.² Investigators performed an exploratory subgroup analysis of patients who did receive adjuvant chemotherapy (n = 167); the HR for DFS was 1.25 (95% CI, 0.76-2.05).¹

Data reported from KEYNOTE-091 reported during a 2022 ESMO Plenary session showed that among allcomers DFS met the primary end point of the study, but was not statistically significant among patients with a TPS of at least 50%.

References

1. FDA approves pembrolizumab as adjuvant treatment for non-small cell lung cancer. FDA. January 26, 2023. Accessed January 26, 2023. https://www.fda.gov/drugs
2. Keytruda. Prescribing information. Merck; 2023. Accessed January 26, 2023.
3. Study of pembrolizumab (MK-3475) vs placebo for participants with non-small cell lung cancer after resection with or without standard adjuvant therapy (MK-3475-091/KEYNOTE-091) (PEARLS). ClinicalTrials.gov. Updated July 17, 2020. Accessed January 26, 2023.