Dr. Herbst on the FDA Approval of Adjuvant Pembrolizumab in NSCLC

Roy S. Herbst, MD, PhD, ensign professor of medicine, medical oncology, professor, pharmacology, director, Center for Thoracic Cancers, Assistant Dean for Translational Research, Yale School of Medicine; deputy director, Yale Cancer Center; chief, Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital, discusses the significance of the FDA approval of adjuvant pembrolizumab (Keytruda) in patients with non–small cell lung cancer (NSCLC).

On January 26, 2023, the FDA approved pembrolizumab in patients with NSCLC following resection and platinum-based chemotherapy. The regulatory decision was based on findings from the phase 3 PEARLS/KEYNOTE-091 trial (NCT02504372), in which the agent produced a median disease-free survival (DFS) of 58.7 months vs 34.9 months with placebo.

The approval of adjuvant pembrolizumab monotherapy in NSCLC is exciting and marks the expansion of indications for this agent across NSCLC treatment settings, Herbst says. In 2016, pembrolizumab was first approved in the frontline setting for patients with metastatic, PD-L1–positive NSCLC. This agent has since gained approval for several other NSCLC indications and is now approved for patients following the resection of stage IB, II, and IIIA disease, Herbst explains.

KEYNOTE-091 showed a 27% improvement in DFS in patients who received adjuvant pembrolizumab vs those who received placebo, regardless of their PD-L1 status, Herbst emphasizes. This benefit was also seen in patients who had previously received adjuvant chemotherapy, Herbst notes.

This approval provides a new adjuvant standard of care for patients with NSCLC, Herbst says. In 2021, the FDA approved the PD-L1 inhibitor atezolizumab (Tecentriq) in this setting based on the phase 3 IMpower010 trial (NCT02486718). However, this approval was limited to patients with stage II to IIIA NSCLC and PD-L1 expression of 1% or higher. The approval of adjuvant pembrolizumab extends to patients with stage IB, II, and IIIA disease and all levels of PD-L1 expression, Herbst explains.

Early data from KEYNOTE-091 show that the use of pembrolizumab in the adjuvant setting can help prevent lung cancer from spreading to sites such as the other lung, the liver, the bones, and the brain after the initial tumor has been resected, Herbst explains. Overall survival data are still immature but will further inform the best use of this agent once reported, Herbst concludes.