The FDA has approved pembrolizumab (Keytruda) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic, HER2-negative gastric or gastroesophageal junction adenocarcinoma.
This article was originally published by OncLive®.
The FDA has approved pembrolizumab (Keytruda) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic, HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.1
The regulatory decision was supported by data from the phase 3 KEYNOTE-859 trial (NCT03675737), which showed that the addition of pembrolizumab to chemotherapy led to statistically significant improvements in overall survival (OS), progression-free survival (PFS), and overall (ORR).1,2
Findings demonstrated that at a median follow-up of 31.0 months (range, 15.3-46.3), patients treated with the pembrolizumab regimen (n = 790) experienced a median OS of 12.9 months (95% CI, 11.9-14.0) vs 11.5 months (95% CI, 10.6-12.1) for those given chemotherapy alone (n = 789; HR, 0.78; 95% CI, 0.70-0.87; P < .0001). The 12- and 24-month OS rates with the combination were 52.7% and 28.2% vs 46.7% and 18.9% with chemotherapy alone, respectively.2
The multicenter, randomized, double-blind, placebo-controlled KEYNOTE-859 trial enrolled patients with histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma of the stomach or GEJ who received no prior treatment, 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 intravenous (IV) pembrolizumab or placebo in combination with investigator's choice of chemotherapy, which consisted of either 800 mg/m2 of 5-flourouracil per day on days 1 through 5 and 80 mg/m2 of cisplatin every 3 weeks, or 1000 mg/m2 of oral capecitabine twice daily on days 1 through 14 plus 130 mg/m2 of IV oxaliplatin every 3 weeks. Pembrolizumab and placebo were administered for up to 35 cycles, equating to approximately 2 years.
OS served as the primary end point. Secondary end points included PFS, ORR, duration of response (DOR), and safety.
Additional findings showed that the pembrolizumab regimen elicited a median PFS of 6.9 months (95% CI, 6.3-7.2) vs 5.6 months (95% CI, 5.5-5.7) with chemotherapy alone (HR, 0.76; 95% CI, 0.67-0.85; P < .0001). The 12- and 24-month PFS rates with the combination were 28.9% and 17.8% vs 19.3% and 9.4% with chemotherapy, respectively.
OS and PFS benefits were similar across subgroups, including those for the stratification factors of geographic region, PD-L1 expression, and choice of chemotherapy.
Pembrolizumab plus chemotherapy generated an ORR of 51.3% (95% CI, 47.7%-54.8%), including a complete response (CR) rate of 9.5% and a partial response (PR) rate of 41.8%. The ORR for chemotherapy plus placebo was 42.0% (95% CI, 38.5%-45.5%), including a CR rate of 6.2% and a PR rate of 35.7%. The median DOR was 8.0 months (range, 1.2+ to 41.5+) with the combination vs 5.7 months (range, 1.3+ to 34.7+) with chemotherapy alone.
Regarding safety, the most common any-grade treatment-related adverse effects (TRAEs) with pembrolizumab and chemotherapy alone, respectively, included nausea (41.4% vs 41.4%), diarrhea (32.1% vs 27.2%), anemia (31.0% vs 26.9%), vomiting (27.4% vs 22.2%), decreased platelet count 25.0% vs 22.5%), decreased neutrophil count (24.6% vs 21.6%), palmar-plantar erythrodysesthesia syndrome (24.1% vs 21.1%), decreased 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%).
Grade 3 to 5 TRAEs occurred in 59.4% (n = 466) of patients who received pembrolizumab vs 51.1% (n = 402) of those who received chemotherapy alone. Serious AEs occurred in 23.4% (n = 184) and 18.6% (n = 146) of patients in the pembrolizumab and chemotherapy alone arms, respectively.
Immune-mediated AEs occurred more commonly in the pembrolizumab arm than in the chemotherapy alone arm, respectively (any grade, 27.1%; grade ≥3, 7.9% vs any grade, 9.3%; grade ≥3, 1.7%).
Additionally, TRAEs led to treatment discontinuation in 26.4% of patients who received pembrolizumab vs 20.1% of those who received chemotherapy alone. Fatalities were reported in 8 patients (1.0%) with pembrolizumab vs 16 (2.0%) with chemotherapy alone.
References
1. FDA approves pembrolizumab with chemotherapy for HER2-negative gastric or gastroesophageal junction adenocarcinoma. News release. FDA. November 16, 2023. Accessed November 16, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-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
Integrating RECIST and Clinician Approaches Boosts NSCLC Research
May 8th 2024Outcomes among patients with stage IV non–small cell lung cancer as evaluated within clinical trials via Response Evaluation Criteria in Solid Tumors (RECIST) and clinician response criteria in observational studies were compared for their concordance and reliability.
Read More
CMS Medicare Final Rule: Advancing Benefits, Competition, and Consumer Protection
May 7th 2024On this episode of Managed Care Cast, we're talking with Karen Iapoce, senior director of government products and programs at ZeOmega, about the recent CMS final rule on Medicare Part D and Medicare Advantage.
Listen
AUA Session Highlights the General Urologist’s Role in Gender-Affirming Care
May 7th 2024During her session, Polina Reyblat, MD, Kaiser Permanente Los Angeles Medical Center, highlighted best practices urologists should incorporate to make transgender and gender-diverse patients comfortable during physical exams and avoid retraumatization.
Read More
Following Roe v Wade Overturn, Research Focuses on Male Contraceptives
May 6th 2024Stephanie T. Page, MD, PhD, UW Medicine Diabetes Institute, presented on ongoing research and growing interest in new male contraceptive options, such as an oral pill and a hormonal transdermal gel, at the American Urological Association 2024 Annual Meeting.
Read More