Phase 3 Trial Shows Pembrolizumab Improves Survival in Patients With Non-Small Cell Lung Cancer

Pembrolizumab (Keytruda; Merck) injection showed a statistically significant improvement in the event-free survival (EFS) of patients with resectable stage 2, 3A, or 3B non-small cell lung cancer (NSCLC) in the KEYNOTE-671 trial. Pembrolizumab, an anti-programmed death receptor-1 (PD-1) therapy, was used as a pre-surgery (neoadjuvant) treatment with chemotherapy, followed by use as post-surgery (adjuvant) single agent in the trial.

“Results from KEYNOTE-671 show that [pembrolizumab] in combination with chemotherapy provided significant improvement in event-free survival, pathological complete response and major pathological response over chemotherapy alone as a perioperative treatment regimen for patients with resectable stage 2, 3A or 3B non-small cell lung cancer,” said Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, in a press release.

Pembrolizumab acts by blocking the interaction between PD-1 and its ligands, which activates immune T lymphocytes (T-cells), increasing the immune system’s ability to detect and fight tumor cells. Among pembrolizumab’s multiple indications across cancer types, it is indicated as a first-line treatment for patients with specific types of metastatic nonsquamous NSCLC; combined with carboplatin and paclitaxel or paclitaxel for metastatic squamous NSCLC; and as a single agent treatment for various types of NSCLC.

Merck investigators conducted the randomized, double-blind, phase 3 KEYNOTE-671 trial to compare a regimen of neoadjuvant pembrolizumab 200 mg intravenous solution and chemotherapy with gemcitabine or pemetrexed followed by single agent pembrolizumab against a regimen of neoadjuvant placebo plus chemotherapy followed by adjuvant placebo in 786 patients with resectable stage 2, 3A, and 3B NSCLC.

The primary endpoints were EFS and overall survival (OS), and key secondary endpoints of pathological compete response and major pathological response. At a prespecified interim analysis, perioperative pembrolizumab and chemotherapy followed by treatment with single agent pembrolizumab significantly and meaningfully improved all designated endpoints. Additionally, the pembrolizumab regimen did not have worse safety outcomes.

NSCLC accounts for 81% of lung cancer cases. Globally, more than 1.8 million people died from lung cancer in 2020. As the leading cause of cancer-related death worldwide, the 5-year OS rate is 25%, which is an improvement from a 4% OS rate less than a decade ago. Screening and early detection contribute to improved OS, but only a small percentage of people in the United States are eligible (5.8% in 2021).

The FDA previously accepted a supplemental Biologics License Application based on these data and set a target action date of October 16, 2023.

“By moving this Keytruda-based regimen into earlier stages of non-small cell lung cancer, we may be able to significantly reduce the risk of recurrence for these patients,” Barr said in the press release.

Reference

Merck. Merck Announces Phase 3 KEYNOTE-671 Trial Met Primary Endpoint of Event-Free Survival (EFS) in Patients With Resectable Stage II, IIIA or IIIB Non-Small Cell Lung Cancer. News Release. March 1, 2023. Accessed March 1, 2023. https://www.merck.com/news/merck-announces-phase-3-keynote-671-trial-met-primary-endpoint-of-event-free-survival-efs-in-patients-with-resectable-stage-ii-iiia-or-iiib-non-small-cell-lung-cancer/