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FDA Approves Keytruda Plus Chemotherapy for Gastric, Gastroesophageal Junction Adenocarcinoma


Merck's pembrolizumab (Keytruda) plus fluoropyrimidine- and platinum-containing chemotherapy approved for the first-line treatment of patients with locally advanced unresectable or metastatic, HER2-negative gastric/GEJ adenocarcinoma.

The FDA has approved Merck’s pembrolizumab (Keytruda) plus fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic, human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.1

Image credit: LASZLO | stock.adobe.com

Image credit: LASZLO | stock.adobe.com

The approval was based on data from the Phase 3 KEYNOTE-859 trial (NCT03675737). Findings from the trial demonstrated that adding Keytruda to chemotherapy produced statistically significant improvements in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR).1,2 At a median follow-up of 31.0 months, median OS was 12.9 months for those administered Keytruda plus chemotherapy compared with 11.5 months for chemotherapy alone.1

“The majority of patients with gastric cancer are diagnosed at an advanced stage, at which point they face a poor prognosis with a five-year survival rate of 6%,” Zev A. Wainberg, MD, professor of medicine at University of California, Los Angeles School of Medicine and co-director of the UCLA GI Oncology Program, said in a press release.1 “This approval of pembrolizumab plus chemotherapy offers patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction cancer a new immunotherapy regimen that has demonstrated the potential to help these patients live longer.”

KEYNOTE-859, a multicenter, randomized, double-blind, placebo-controlled study, included patients with histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the stomach or GEJ who were not previously treated, had a known PD-L1 status, were HER2-negative, and had an ECOG performance status of 0 or 1.

Patients were randomly assigned 1:1 to receive 200 mg of Keytruda or placebo plus investigator's choice of chemotherapy of either 800 mg/m2 of 5-flourouracil per day on days one through five and 80 mg/m2 of cisplatin every three weeks, or 1000 mg/m2 of oral capecitabine twice daily on days one through 14 plus 130 mg/m2 of IV oxaliplatin every three weeks. Keytruda and placebo were administered for up to 35 cycles, which equaled approximately two years. The primary endpoint of KEYNOTE-859 was OS, with secondary end points of PFS, ORR, duration of response (DOR), and safety.

The combination produced a median PFS of 6.9 months compared with 5.6 months with chemotherapy alone. PFS rates at 12- and 24-months with the Keytruda combination were 28.9% and 17.8% compared with 19.3% and 9.4% with chemotherapy, respectively. The treatment combination produced an ORR of 51.3%, with a complete response (CR) rate of 9.5% and a partial response (PR) rate of 41.8% compared with an ORR of 42.0%, a CR rate of 6.2%, and a PR rate of 35.7% in the placebo cohort. Median DOR was 8.0 months in patients administered the Keytruda combination compared with 5.7 months chemotherapy alone.

In terms of safety, the most common any-grade treatment-related adverse effects (TRAEs) in patients administered Keytruda vs. chemotherapy alone, respectively, were nausea (41.4% vs. 41.4%), diarrhea (32.1% vs. 27.2%), anemia (31.0% vs. 26.9%), vomiting (27.4% vs. 22.2%), reduced platelet count 25.0% vs. 22.5%), reduced neutrophil count (24.6% vs. 21.6%), palmar-plantar erythrodysesthesia syndrome (24.1% vs. 21.1%), diminished appetite (21.4% vs. 21.3%), fatigue (20.0% vs. 20.8%), peripheral neuropathy (19.1% vs. 20.8%), neutropenia (18.1% vs. 17.2%), increased aspartate aminotransferase (17.7% vs. 13.0%), and peripheral sensory neuropathy (17.5% vs. 16.6%). Serious AEs occurred in 23.4% of patients administered Keytruda compared with 18.6% of patients in the placebo cohort.

“At Merck, we have a comprehensive development program across a broad range of gastrointestinal cancers with the goal of providing meaningful new options to patients and their healthcare providers,” said Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, in a press release.1 “This latest approval of a Keytruda-based treatment option is an important milestone for patients with advanced HER2-negative gastric or GEJ adenocarcinoma and reinforces Merck’s commitment to addressing the needs of these patients in the US.”


1. FDA Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy as First-Line Treatment for Locally Advanced Unresectable or Metastatic HER2-Negative Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma. Merck. News release. November 16, 2023. Accessed November 17, 2023. https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-plus-chemotherapy-as-first-line-treatment-for-locally-advanced-unresectable-or-metastatic-her2-negative-gastric-or-gastroesophageal-junction/

2. Rha SY, Wyrwicz LS, Weber Y, et al. Pembrolizumab plus chemotherapy as first-line therapy for advanced HER2-negative gastric or gastroesophageal junction cancer: phase 3 KEYNOTE-859 study. Presented at: ESMO Virtual Plenary Series; February 16-17, 2023. doi:10.1016/j.annonc.2023.01.006.

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