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Background Molecular subtypes including mismatch repair-deficient (MMR-D) affect the efficacy of immune checkpoint inhibitors in patients (pts) with advanced gastric cancer (AGC). However, the association between the subtypes and efficacy of standard chemotherapy remains unclear. Methods AGC pts received chemotherapy from October 2015 to July 2018 with available molecular features were analyzed in this study. We investigated the efficacy of first- (fluoropyrimidine + platinum ± trastuzumab) or second-line (taxanes ± ramucirumab or irinotecan) chemotherapy according to four subtypes: MMR-D, EBV+, HER2+ and others (all-negative). Results Total 410 pts were analyzed: MMR-D, n = 24 (5.9%); EBV+, n = 16 (3.9%); HER2+, n = 56 (13.7%); all-negative, n = 314 (76.6%) with no overlapping between molecular subgroups. Among 285 pts receiving standard first-line chemotherapy, the median PFS were 4.2, 6.0, 7.5, 7.6 months and the ORR were 31, 62, 62, 51% in MMR-D, EBV+, HER2+, and all-negative groups, respectively. Multivariate analysis showed shorter PFS in MMR-D group vs. all-negative (HR 1.98, 95% confidence interval, 1.13-3.47; p = 0.016), while other comparison between subgroups did not show significant difference. In 262 pts receiving second-line chemotherapy, there was no significant difference in efficacy among the four subtypes: the median PFS were 3.9, 6.6, 3.7, 3.9 months and the ORR were 37, 43, 14, 32% in MMR-D, EBV+, HER2+ and all-negative groups, respectively. Twelve MMR-D pts received subsequent immune checkpoint inhibitors, which showed higher ORR (64%) and longer PFS (median PFS: 13.0 months) compared with earlier line chemotherapy. Conclusion MMR-D might result in shorter PFS with first-line chemotherapy for AGC compared with other subgroups. Meanwhile immune checkpoint inhibitors achieved a longer PFS than standard chemotherapy in most MMR-D pts, supporting earlier use of immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Background Nivolumab showed a survival benefit compared to placebo in patients (pts) with advanced gastric cancer (AGC) after two or more previous lines of chemotherapy. However, it remains unclear whether to use nivolumab or irinotecan in AGC pts as a third- or later-line treatment. Meanwhile, ECOG PS or molecular characteristics are associated with outcomes after PD1 blockade for AGC (Shitara K, et al, Lancet 2018; Mishima S, et al, JITC 2019). Methods AGC Pts treated with nivolumab or irinotecan after fluoropyrimidine based regimens and taxanes from May 2016 to November 2018 were analyzed. Subgroup analysis was conducted according to ECOG PS or other clinicopathological characteristics. Results Total 128 pts (58 in the nivolumab group and 70 in the irinotecan group) were included in this study. The median PFS were both 1.9 months (HR 0.85; 95% CI, 0.58-1.27). Nivolumab showed a longer PFS than that of irinotecan in pts with ECOG PS of 0 (N = 66), with median PFS of 3.1 vs. 2.0 months (HR, 0.53; 95% CI, 0.30-0.94), while irinotecan showed a trend of longer PFS in pts with ECOG PS of 1 or more (N = 62; median 1.1 vs. 1.8 months; HR 1.51; 95% CI, 0.87-2.63; p for interaction = 0.009). Interaction between treatment effect and ECOG PS was consistent if it was limited to microsatellite stable AGC. Conclusions ECOG PS was associated with outcomes after nivolumab or irinotecan in AGC pts as a third- or later-line, which warrants further evaluation in a larger cohort. Biomarker analysis will be presented at the meeting. [ABSTRACT FROM AUTHOR]

Background Nivolumab (NIVO) showed a survival benefit compared to placebo in patients (pts) with advanced gastric cancer (AGC) after two or more previous lines of chemotherapy. It has been reported that prior treatment with immune check point inhibitors might improve responses to salvage chemotherapy without unexpected safety signals in non-small cell lung cancer. However, safety and efficacy of irinotecan (IRI) administered after NIVO in pts with AGC remains unclear. Methods Pts with AGC treated with IRI after NIVO (cohort A) or IRI before NIVO (cohort B) from September 2017 to December 2018 were analyzed in this study. Clinical outcomes after IRI were compared between two groups. Results A total of 44 pts (14 in cohort A and 31 in cohort B) were included in this study. Common grade 3 or worse adverse events in cohort A were leukocytopenia (21%), neutropenia (14%), thrombocytopenia (7%) and diarrhea (7%), which were not significantly different in cohort B. No immune related adverse events occurred in cohort A. The ORR-IRI was 21% in cohort A and 16% in cohort B (p = 0.48), and the median PFS-IRI was 2.67 and 2.37 months (HR = 0.87, p = 0.68), respectively. In cohort A, the PFS of IRI was longer than that of NIVO in 9 of 14 pts (64%). Conclusions IRI administered after NIVO was manageable without unexpected adverse events. Although prior NIVO did not seem to improve responses to IRI, it was notable that IRI showed a longer PFS than that of prior NIVO in a substantial number of pts. [ABSTRACT FROM AUTHOR]