Real-world effectiveness of drugs newly approved in Japan on survival in patients with advanced gastric cancer.

322 Background: Ramucirumab (RAM), nivolumab (NIVO), and trifluridine/tipiracil (FTD/TPI) were approved for advanced gastric cancer (AGC) between 2010 and 2020 in Japan. However, the impact of these newly approved drugs on survival in the real-world clinical setting is not clear. Methods: This retrospective study investigated the effectiveness of RAM, NIVO, and FTD/TPI in patients with performance status (PS) 0 to 2 who received doublet or triplet chemotherapy including platinum agents in first-line (1L) for advanced gastric adenocarcinoma at our hospital between 2010 and 2020. Patients were divided into two groups before or after 2017 to compare the effectiveness. Results: From a total of 825 patients, 533 were assigned to the pre-2017 group and 292 to the post-2017 group. Baseline characteristics of the pre- and post-2017 groups were, respectively, as follows: median age, 64 (range, 20-83) and 65 (25-85) years; PS 0, 206 (39%) and 89 (31%), and PS 1-2, 327 (61%) and 202 (69%); peritoneal metastasis, 334 (63%) and 189 (65%); liver metastasis, 157 (30%) and 68 (23%); and HER2 positive, 82 (15%) and 57 (20%). There was no difference in the proportion of fluoropyrimidine and platinum agents between the two groups. For the pre- and post-2017 groups, 1L chemotherapy comprised fluoropyrimidine plus platinum agents (FP) for 71% and 68% of patients, FP plus taxanes for 15% and 1%, FP plus trastuzumab for 11% and 15%, and FP plus immune checkpoint inhibitors (ICIs) for 1% and 10%, respectively. Taxanes and irinotecan were used significantly more often in any treatment line in the pre-2017 group (taxanes, 74% vs. 64%, p<0.01; irinotecan, 32% vs. 7%, p<0.01), whereas RAM, ICIs, and FTD/TPI were used significantly more often in any line in the post-2017 group (RAM, 50% vs. 17%, p<0.01; ICIs, 48% vs. 9%, p<0.01; FTD/TPI, 6% vs. 0%, p<0.01). Overall survival was significantly longer in the post-2017 group than in the pre-2017 group (median, 16.9 months vs. 13.8 months, HR 0.74, p<0.01). Progression-free survival did not differ between the pre- and post-2017 groups in relation to 1L (median, 6.0 vs. 5.9 months, p=0.74); second-line treatment (median, 3.0 months [95%CI, 2.6-3.3] vs. 3.1 months [95%CI, 2.3-3.6]; HR 0.96 [95%CI, 0.82-1.14], p=0.57); third-line treatment (median, 2.1 months [95%CI, 1.8-2.5] vs. 1.8 months [95%CI, 1.4-2.1]; HR 1.03 [95%CI, 0.82-1.29], p=0.80); or fourth-line treatment (median, 1.9 months [95%CI, 1.7-2.5] vs. 1.8 months [95%CI, 1.5-2.8]; HR 0.85 [95%CI, 0.57-1.25], p=0.39). Rates of second-, third-, and fourth-line treatment in the pre- and post-2017 groups were 83% and 79% (p=0.23), 45% and 56% (p<0.01), 16% and 22% (p=0.07), respectively. Conclusions: Newly approved drugs in salvage-line treatment of AGC may have contributed to prolonged survival.