Combined PD-1, HER2 blockade extends PFS in gastric, gastroesophageal junction cancers
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Key takeaways:
- Combined PD-1 and HER2 blockade improved PFS, response rate and response durability.
- Patients with PD-L1 combined positive scores of 1 or higher derived the most benefit.
MADRID — Adding pembrolizumab to trastuzumab and chemotherapy extended PFS for patients with unresectable HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma, study results presented at ESMO Congress showed.
The combination also increased response rate and durability of response, according to the findings, published simultaneously in The Lancet Oncology.
The benefit appeared most pronounced among patients with PD-L1 combined positive scores of 1 or higher.
“These efficacy and safety data continue to support use of this regimen in the first-line setting,” Yelena Y. Janjigian, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, and colleagues wrote.
There is limited evidence about the impact combined PD-1 and HER2 blockade with chemotherapy may have on disease progression or survival in HER2-positive gastro-esophageal cancer, according to study background.
The randomized phase 3 KEYNOTE-811 study assessed the addition of the anti-PD-1 antibody pembrolizumab (Keytruda, Merck) to first-line trastuzumab and chemotherapy for adults with treatment-naive locally advanced or metastatic HER2-positive gastro-esophageal junction adenocarcinoma.
The analysis included 698 patients (81% men) treated at 168 centers in 20 countries.
Researchers randomly assigned 350 patients to 200 mg IV pembrolizumab plus standard chemotherapy and trastuzumab every 3 weeks. The other 348 received placebo plus chemotherapy and trastuzumab.
Treatment continued for 35 cycles, or until disease progression, unacceptable toxicity, or participant- or investigator-initiated withdrawal.
PFS and OS per intention-to-treat analysis served as dual primary endpoints. Investigators also assessed safety for all patients who received at least one dose of assigned treatment.
Results of a second interim analysis — performed after median follow-up of 28.3 months in the pembrolizumab group and 28.5 months in the placebo group — showed longer median PFS with pembrolizumab (10 months vs. 8.1 months; HR = 0.72; 95% CI, 0.6-0.87). At that time, the difference in median OS between the pembrolizumab and placebo groups had not reached statistical significance (20 months vs. 16.9 months; HR = 0.87; 95% CI, 0.72-1.06).
At ESMO, Janjigian reported findings from a third protocol-specified interim analysis, performed after median follow-up of 38.4 months (interquartile range, 29.55-44.4) in the pembrolizumab group and 38.6 months (interquartile range, 30.2-44.4) in the placebo group.
At data cutoff, 82% of those assigned pembrolizumab and 88% of those assigned placebo had discontinued treatment, primarily because of disease progression.
Results continued to show longer median PFS with pembrolizumab (10 months vs. 8.1 months; HR = 0.73; 95% CI, 0.61-0.87). Researchers reported a numerical improvement in median OS but the difference did not reach statistical significance (20 months vs. 16.8 months; HR = 0.84; 95% CI, 0.7-1.01). Follow-up for OS will continue, and results will be updated at the final analysis.
The effect of the pembrolizumab regimen appeared “enhanced” among patients whose tumors had PD-L1 combined positive score of 1 or more, researchers wrote. They reported little to no benefit among patients whose tumors had PD-L1 combined positive scores less than 1.
A higher percentage of patients assigned pembrolizumab experienced grade 3 or higher treatment-related adverse events (58% vs. 51%). Four patients assigned pembrolizumab and three assigned placebo died due to treatment-related adverse events.
The most common any-grade treatment-related adverse events included diarrhea (47% for pembrolizumab vs. 42% for placebo), nausea (44% in each group) and anemia (31% vs. 33%).
References:
- Janjigian YY, et al. Abstract 1511O. Presented at: European Society for Medical Oncology Congress; Oct. 20-24, 2023; Madrid.
- Janjigian YY, et al. Lancet Oncol. 2023;doi:10.1016/S0140-6763(23)02033-0.
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Janjigian YY, et al. Abstract 1511O. Presented at: European Society for Medical Oncology Congress; Oct. 20-24, 2023; Madrid.
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