|The following article features coverage from the ASCO Gastrointestinal Cancers Symposium 2022. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
Adding pembrolizumab to chemotherapy does not improve survival outcomes for patients with PD-L1-positive, advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to updated results from the KEYNOTE-062 trial.
These results were presented at the ASCO Gastrointestinal Cancers Symposium 2022 by Zev A. Wainberg, MD, of University of California, Los Angeles.
KEYNOTE-062 (ClinicalTrials.gov Identifier: NCT02494583) included 763 patients with locally advanced, unresectable, or metastatic gastric or GEJ adenocarcinoma. All patients had a PD-L1 combined positive score (CPS) of 1 or higher.
The patients were randomly assigned to receive pembrolizumab monotherapy (253 patients treated), pembrolizumab plus chemotherapy (251 treated), or placebo plus chemotherapy (244 treated). Chemotherapy consisted of cisplatin and fluorouracil or capecitabine.
At a median follow-up of 54.3 months, the overall survival (OS) with pembrolizumab monotherapy was noninferior to the OS with chemotherapy alone in the overall cohort. The median OS was 10.6 months with pembrolizumab and 11.1 months with chemotherapy (hazard ratio [HR], 0.90; 95% CI, 0.75-1.08).
The researchers noted a “clinically meaningful” OS benefit with pembrolizumab in patients with a CPS of 10 or higher. In this group, the median OS was 17.4 months with pembrolizumab alone and 10.8 months with chemotherapy alone (HR, 0.62; 95% CI, 0.45-0.86).
When the researchers compared pembrolizumab plus chemotherapy with chemotherapy alone, neither OS nor progression-free survival (PFS) results were superior with the addition of pembrolizumab, regardless of CPS.
“In the combination arms, not much has changed over the last 2 years,” Dr Wainberg said. “We still see, unfortunately and perplexingly to some extent, a negative impact of pembrolizumab plus chemotherapy over chemotherapy alone.”
Among patients with a CPS of 1 or higher, the median OS was 12.5 months with pembrolizumab plus chemotherapy and 11.1 months with chemotherapy alone (HR, 0.85; 95% CI, 0.71-1.02). Among patients with a CPS of 10 or higher, the median OS was 12.3 months and 10.8 months, respectively (HR, 0.76; 95% CI, 0.56-1.03).
Among patients with a CPS of 1 or higher, the median PFS was 6.9 months with pembrolizumab plus chemotherapy and 6.5 months with chemotherapy alone (HR, 0.84; 95% CI, 0.70-1.01). Among patients with a CPS of 10 or higher, the median PFS was 5.8 months and 6.2 months, respectively (HR, 0.71; 95% CI, 0.52-0.96).
Pembrolizumab was associated with a lower rate of grade 3-5 adverse events (AEs) compared with chemotherapy alone or chemotherapy plus pembrolizumab — 50.4%, 82.4%, and 84.8%, respectively.
However, the rate of fatal AEs was higher in the pembrolizumab arm than in the chemotherapy or combination arms — 9.8%, 5.3%, and 6.8%, respectively.
Disclosures: This research was supported by Merck Sharp & Dohme Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
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Wainberg ZA, Shitara K, Van Cutsem E, et al. Pembrolizumab with or without chemotherapy versus chemotherapy alone for patients with PD-L1-positive advanced gastric or gastroesophageal junction adenocarcinoma: Update from the phase 3 KEYNOTE-062 trial. Presented at ASCO GI 2022; January 20-22, 2022. Abstract 243.