Dr Janjigian on Final OS Results With Pembrolizumab Plus Trastuzumab and Chemo in HER2+ Gastric/GEJ Cancer

Yelena Y. Janjigian, MD, chief, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, discusses results from final overall survival (OS) analysis of the phase 3 KEYNOTE-811 trial (NCT03615326) in patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

KEYNOTE-811 investigated the combination of pembrolizumab (Keytruda) plus trastuzumab (Herceptin) and chemotherapy vs placebo plus trastuzumab and chemotherapy in this population. In 2021, the FDA granted accelerated approval to the combination for this indication based on previously reported findings from the first interim analysis of KEYNOTE-811, in which the investigational regimen improved ORR by 22% vs the control arm.

Final OS data from KEYNOTE-811 presented at the 2024 ESMO Congressdemonstrated a 20% reduction in the risk of death among patients treated with pembrolizumab plus trastuzumab and chemotherapy (n = 350) vs those who received trastuzumab and chemotherapy alone (n = 348), Janjigian explains. After a median follow-up of 50.2 months (Range, 31.1-64.4), the median OS was 20.0 months (95% CI, 17.8-22.1) in the pembrolizumab arm compared with 16.8 months (95% CI, 14.9-18.7) in the control arm (HR, 0.80; 95% CI, 0.67-0.94; P = .004). The 36-month OS rate was also higher with pembrolizumab (28%) than with the control arm (23%).

Among patients with a PD-L1 combined positive score (CPS) of 1 or greater, which comprised 85% of patients across both arms, the median OS was 20.1 months (95% CI, 17.9-22.9) with pembrolizumab vs 15.7 months (95% CI, 0.13.5-18.5) with placebo. Progression-free survival (PFS) was similarly improved, with a median PFS of 10.9 months (95% CI, 8.5-12.5) vs 7.3 months (95% CI, 6.6-8.4), respectively, (HR, 0.72; 95% CI, 0.60-0.87). The overall response rate (ORR) was also notably higher with pembrolizumab, at 73.2% vs 58.4% in the control arm, she reports.

At the final analysis, most patients had discontinued treatment due to disease progression, though 11 patients remained on treatment in the pembrolizumab arm compared with 4 in the placebo group. The data reaffirm pembrolizumab plus trastuzumab and chemotherapy as a new standard of care in first-line treatment for patients with unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma with PD-L1 CPS of 1 or higher, Janjigian concludes.