CheckMate-649 study findings continue to support frontline nivolumab and chemotherapy for patients with advanced gastric, gastroesophageal junction cancer, and esophageal adenocarcinoma.
Updated findings from the phase 3 CheckMate-649 study (NCT02872116) continue to support the combination of nivolumab and chemotherapy as frontline treatment for patients with advanced gastric, gastroesophageal junction cancer, and esophageal adenocarcinoma.1
These 3-year follow-up data shared during the 2023 Gastrointestinal Cancers Symposium showed that at a minimum follow-up of 36.2 months, the median overall survival (OS) was 14.4 months (95% CI, 13.1-16.2) with nivolumab plus chemotherapy (n = 473) and 11.1 months (95% CI, 10.0-12.1) with chemotherapy alone (n = 482) in the population of patients with a PD-L1 combined positive score (CPS) of 5 or higher (HR, 0.70; 95% CI, 0.61-0.81). The 3-year OS rates were 21% and 10%, respectively.
In the all-randomized population, the addition of nivolumab to chemotherapy (n = 789) resulted in a 21% reduction in the risk of death vs chemotherapy alone (n = 792). The median OS was 13.7 months (95% CI, 12.4-14.5) and 11.6 months (95% CI, 10.9-12.5), respectively (HR, 0.79; 95% CI, 0.71-0.88). The 3-year OS rates were 17% and 10%, respectively.
The progression-free survival (PFS) benefit achieved with nivolumab plus chemotherapy over chemotherapy alone was also maintained with longer follow-up in both populations. In the subset of patients with a PD-L1 CPS of at least 5, the median PFS was 8.3 months (95% CI, 7.0-9.3) in the investigative arm vs 6.1 months (95% CI, 5.6-6.9) in the control arm (HR, 0.70; 95% CI, 0.60-0.81). The 3-year PFS rates were 13% and 8%, respectively. In the all-randomized population, the median PFS was 7.7 months (95% CI, 7.1-8.6) and 6.9 months (95% CI, 6.7-7.2), respectively (HR, 0.79; 95% CI, 0.71-0.89). In this group, the 3-year PFS rates were 11% and 7%, respectively.
Across all PD-L1 CPS subsets analyzed, the objective response rate (ORR) reported with nivolumab plus chemotherapy continued to be higher than that achieved with chemotherapy alone. In the subset of patients with a PD-L1 CPS of 5 or higher, the ORR with nivolumab plus chemotherapy (n = 378) was 60% (95% CI, 55%-65%) vs 45% (95% CI, 40%-50%) with chemotherapy alone (n = 390). The median duration of response (DOR) was 9.6 months (95% CI, 8.2-12.4) and 7.0 months (95% CI, 5.6-7.9), respectively.
In the all-randomized population, the ORR in the investigative arm (n = 602) was 58% (95% CI, 54%-62%) vs 46% (95% CI, 42%-50%) in the control arm. In this group, the median DOR was 8.5 months (95% CI, 7.7-9.9) and 6.9 months (95% CI, 5.8-7.2), respectively.
“At 36 months, we still see a meaningful improvement in all efficacy end points, such as OS and PFS, both in first line and subsequent therapies, and of course, ORR. We [also] see no new safety signals,” said Yelena Y. Janjigian, MD, who is the lead study author of the trial, and the chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center, in a presentation of the data. “And so, [these] data, in conjunction with the safety data, continue to support the use of nivolumab plus chemotherapy in the first-line setting [in this population].”
In April 2021, the FDA approved nivolumab for use in combination with select types of chemotherapy in the frontline treatment of this patient population based on earlier findings from CheckMate-649.2 “CheckMate-649 changed practice for many patients worldwide,” Janjigian underscored.
With a minimum of 12 months of follow-up, the median OS was 14.4 months (95% CI, 13.1-16.2) with nivolumab plus chemotherapy vs 11.1 months (95% CI, 10.0-12.1) with chemotherapy alone in the subgroup of patients with a PD-L1 CPS of at least 5 (HR, 0.71; P < .0001).3 The median PFS in the investigative and control arms at that time point was 7.7 months (95% CI, 7.0-9.2) and 6.0 months (95% CI, 5.6-6.9), respectively (HR, 0.68; P < .0001).3 The combination of nivolumab and chemotherapy continued to showcase clinically meaningful improvements over chemotherapy alone at a minimum of 24 months of follow-up.4
The open-label, randomized, global phase 3 trial enrolled patients with previously untreated, unresectable, advanced or metastatic gastric/GEJ/esophageal adenocarcinoma who had an ECOG performance status of 0 or 1 and no known HER2 positivity.
Participants were enrolled from 175 hospitals and cancer centers throughout 29 countries and were randomly assigned 1:1:1 to the following treatment arms where they received:
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