Correlation between PD-L1 CPS and clinical outcomes in patients treated with first-line nivolumab plus chemotherapy for advanced gastric or gastroesophageal junction cancer: A multi-center retrospective study in Japan.

364 Background: The CheckMate 649 trial showed the superiority of first-line nivolumab plus chemotherapy (Nivo-CT) compared with chemotherapy alone for advanced gastric and gastroesophageal junction (GEJ) cancer with a programmed cell death ligand 1 (PD-L1) combined positive score (CPS) >5, while survival benefit was poor in PD-L1 CPS <1 and <5. However, there were few studies on correlation between PD-L1 CPS and efficacy of first-line Nivo-CT for advanced gastric or GEJ cancer in real world data. Methods: This multi-center retrospective study included patients with histologically confirmed advanced gastric or GEJ cancer who were started on first-line Nivo-CT between December 2021 and December 2023. PD-L1 CPS was assessed before the start of Nivo-CT by classified into three groups at each center: <1, 1~5 and >5, using the Dako PD-L1 immunohistochemistry 28-8 pharmDx assay. The efficacy was evaluated by overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Results: A total of 271 patients were included (median age, 70 [range 18–85] years; male/female, 64/36%; performance status (PS) 0/1/2, 47/49/4%; primary tumor site gastric/GEJ, 90/10%; status unresectable/recurrent, 81/19%; histology intestinal/diffuse, 30/70%). PD-L1 CPS status were evaluated 234 (86%) patients and PD-L1 CPS <1, 1~5 and >5 was found in 35 (15%), 76 (33%) and 123 (53%) patients, respectively. Median follow-up time was 11.3 (range 1-30) months. The median PFS was 9.7 (95%CI, 5.9-16.3), 8.8 (95%CI, 7.2-13.0) and 6.3 (95%CI, 5.3-9.0) months in the patient with PD-L1 CPS <1, 1~5 and >5, respectively. The median OS was 18.7 (95%CI, 17.4-NA), 23.4 (95%CI, 17.7-NA) and 18.3 (95%CI, 13.3-22.5) months, and the ORR were 30.8, 66.7 and 61.3% (p = 0.075) in the patient with PD-L1 CPS <1, 1~5 and >5, respectively. Liver metastases were found in 43 (35.0%) of the patients with PD-L1 CPS >5, significantly more than in the patients with PD-L1 CPS <5 (p < 0.001). Multivariate analysis indicated that PD-L1 CPS status was not associated with prognosis (PD-L1 CPS ≥5 vs. <1, HR 1.18 [95%CI, 0.75-1.86], p = 0.48). In the overall population, grade ≥3 adverse events were observed in 102 (37.6%) patients and grade ≥3 immune-related adverse events were observed in 26 (9.6%) patients. Conclusions: There were no significant differences in prognosis and response between PD-L1 CPS in first-line Nivo-CT for advanced gastric or GEJ cancer in real world data.