DISCUSSION
death, TRAEs, PD‐L1
PRIMARY TUMOR, ADVERSE EVENTS, CPS, SEPARATION, DISEASE CHARACTERISTIC
Chinese patients who received nivolumab plus chemotherapy experienced clinically meaningful improvements in OS and PFS per BICR vs chemotherapy alone in the PD‐L1 CPS ≥5 and PD‐L1 CPS ≥1 groups and in the all randomized population. There was early and sustained separation of OS and PFS curves and a higher percentage of patients alive at 12 months in the nivolumab plus chemotherapy group vs the chemotherapy group, suggesting rapid and durable clinical benefit with nivolumab plus chemotherapy. OS consistently favored nivolumab plus chemotherapy vs chemotherapy across multiple prespecified subgroups, including by PD‐L1 CPS subgroups. Objective response rates were higher and responses were more durable in the nivolumab plus chemotherapy group compared with those in the chemotherapy group for patients with PD‐L1 CPS ≥5 and for all randomized patients. Nivolumab plus chemotherapy had an acceptable safety profile and was consistent with the known safety profiles of the individual treatment components with no new safety signals identified.In the global study population (n = 1581), nivolumab plus chemotherapy demonstrated superior OS vs chemotherapy with a 29% reduction in the risk of death and 3.3‐month improvement in median OS for patients with PD‐L1 CPS ≥5, and a 20% reduction in the risk of death and 2.2‐month improvement in median OS for all randomized patients. Clinically meaningful OS benefit with nivolumab plus chemotherapy vs chemotherapy was also observed in the Chinese subgroup (n = 208) with a 46% reduction in risk of death and 5.9‐month improvement in median OS in patients with PD‐L1 CPS ≥5 and a 39% reduction in risk of death and 4.0‐month improvement in median OS in all randomized patients. While median OS and PFS in the chemotherapy group were shorter in Chinese patients compared with the global study population these were consistent with reports in other global trialsSafety was comparable between the Chinese subgroup and global study population with grade 3 to 4 TRAEs reported for 65% of Chinese patients and 59% of the global study population treated with nivolumab plus chemotherapy. However, rates of any‐grade TRAEs leading to discontinuation from nivolumab plus chemotherapy were higher in Chinese patients than the global study population (51% and 36% of patients, respectively). The type and severity of TRAEs observed in Chinese patients were similar to those observed in the global study population. Despite the increased incidence of TRAEs leading to discontinuation, median duration of treatment was comparable between the global study population and the Chinese subgroup, indicating that TRAEs leading to discontinuation likely did not have a substantial effect on treatment duration in this subgroup.While it is important to note that this analysis was not designed as a formal comparison with the global study population, differences in baseline disease characteristics and practice patterns, including subsequent therapies, were observed. Chinese patients, when compared with the global study population, respectively, had numerically higher rates of ECOG PS 1 (75% vs 58%) and GC as the primary tumor location at initial diagnosis (89% vs 70%). In the nivolumab plus chemotherapy group, a higher percentage of Chinese patients received XELOX compared with the global study population (81% vs 46%, respectively). The rate of subsequent therapy in the Chinese subgroup was also higher than the overall population in both the nivolumab plus chemotherapy (47% vs 38%, respectively) and chemotherapy (59% vs 41%) groups.The randomized phase III trial ORIENT‐16 evaluated the PD‐1 inhibitor sintilimab plus chemotherapy vs chemotherapy in Chinese patients with previously untreated, unresectable advanced, recurrent or metastatic GC/GEJC.It is important to consider the potential limitations of this study and the Chinese subgroup analysis. CheckMate 649 was an open‐label trial. A lack of blinding may result in differences in assessments such as causality of adverse events. The open‐label design was determined to be appropriate due to the use of multiple treatments and dosing regimens. It was not expected that the management of TRAEs (with standard treatment algorithms) or centrally assessed primary endpoints (eg, PFS) would be affected by bias. The Chinese subgroup was relatively small in comparison to the global population (n = 208 vs n = 1581, respectively).