Updated Data in KEYNOTE-061: Pembrolizumab in Previously Treated Gastric or Gastroesophageal Junction Adenocarcinoma

The phase III KEYNOTE-061 trial investigating pembrolizumab (Keytruda) as a second-line treatment for patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma did not meet its primary endpoint of overall survival (OS) (hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.66–1.03; P = .042 [one-sided]) in patients whose tumors expressed programmed cell death ligand 1 (PD-L1) (combined positive score [CPS] ≥ 1). Additionally, progression-free survival (PFS) in the PD-L1–positive population did not show statistical significance. The safety profile observed in KEYNOTE-061 was consistent with that observed in previously reported studies of pembrolizumab; no new safety signals were identified.

In September 2017, the U.S. Food and Drug Administration (FDA) approved pembrolizumab as a third-line treatment for previously treated patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction cancer whose tumors express PD-L1 (CPS ≥ 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy.

The current indication remains unchanged and pembrolizumab will continue to be evaluated for gastric or GEJ adenocarcinoma through KEYNOTE-062, a phase III clinical trial studying pembrolizumab as a monotherapy or in combination with chemotherapy as first-line treatment for patients with PD-L1–positive advanced gastric or gastroesophageal junction cancer, and with KEYNOTE-585, a phase III trial studying pembrolizumab in combination with chemotherapy in a neoadjuvant/adjuvant setting.

About KEYNOTE-061

KEYNOTE-061 is a randomized, open-label, pivotal phase III study investigating pembrolizumab as a monotherapy vs paclitaxel in patients with advanced gastric or GEJ adenocarcinoma whose disease progressed after first-line treatment with platinum and fluoropyrimidine doublet therapy. The primary endpoints are PFS and OS in patients whose tumors express PD-L1 (CPS > 1); secondary endpoints include PFS, OS, and overall response rate (ORR) in patients regardless of PD-L1 expression.

The study randomized 592 patients to receive pembrolizumab (200 mg fixed dose every 3 weeks) or paclitaxel (80 mg/m2 on days 1, 8, and 15 of each 28-day cycle).

The study was designed to first evaluate efficacy in patients whose tumors expressed PD-L1. If efficacy signals were observed and PFS and OS were positive in this subset of patients, further analysis was planned in the overall population.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.