KEYNOTE-811: Final OS for Pembrolizumab Plus Trastuzumab, Chemo for HER2-Positive G/GEJ Adenocarcinoma

First-line pembrolizumab plus trastuzumab and chemotherapy provides a statistically significant and clinically meaningful improvement in overall survival (OS) compared to placebo plus trastuzumab and chemotherapy in patients with HER2-positive advanced, unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, according to the final overall survival analysis of KEYNOTE-811.

Data are presented by Dr. Sara Lonardi as a proffered paper at the European Society for Medical Oncology Congress 2024.

Previous reports of the phase 3 KEYNOTE-811 study showed that first-line pembrolizumab plus trastuzumab and chemotherapy improves progression-free survival (PFS) and objective response rate (ORR) with durable responses compared with placebo plus trastuzumab and chemotherapy in patients with HER2-positive advanced, unresectable or metastatic G/GEJ adenocarcinoma, particularly in patients with tumors of PD-L1 combined positive score of at least one.

In KEYNOTE-811, 698 eligible patients were randomized (1:1) to the pembrolizumab arm (200 mg IV every 3 weeks; n=350) or the placebo arm (IV every 3 weeks; n=348). Each arm was given trastuzumab plus chemotherapy (5-FU and cisplatin or capecitabine and oxaliplatin). Patients were at least 18 years of age with treatment-naïve HER2-positive unresectable or metastatic G/GEJ adenocarcinoma, irrespective of PD-L1 status.

The dual primary endpoints were PFS and OS. The data cutoff at final analysis was March 20, 2024.

After a median follow-up of 50.2 months, the median PFS continued to be longer in the pembrolizumab arm than the placebo arm (10.0 months vs 8.1 months, respectively; HR, 0.73; 95% CI, 0.61-0.87). In patients with tumors of PD-L1 combined positive score of at least one, the median PFS was 10.9 months versus 7.3 months, respectively (HR, 0.72; 95% CI, 0.60-0.87).

At the final analysis, median OS was significantly improved for patients in the pembrolizumab arm (20.0 months vs 16.8 months, respectively; HR, 0.80; 95% CI, 0.67-0.94; P=.004). This P value was less than the prespecified boundary of 0.0201, Dr. Lonardi and colleagues noted.

A similar trend was observed for patients with tumors of PD-L1 combined positive score of at least one; the median OS was 20.1 months versus 15.7 months, respectively (HR, 0.79; 95% CI, 0.66-0.95).

The ORR was 72.6% versus 60.1%, respectively, they added. Grade 3 or higher treatment-related adverse event rates were 59% vs 51%, respectively.

“These data support the approval of pembrolizumab plus trastuzumab and chemotherapy in patients with HER2-positive metastatic G/GEJ cancer and confirm this regimen as standard of care in the first-line setting,” study authors concluded.