Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial

Abstract

No survival benefit was observed upon adding CDDP to CPT-11 after S-1 monotherapy failure.

2300 A multicenter randomized phase II study of docetaxel vs. docetaxel plus cisplatin vs. docetaxel plus S-1 as second-line chemotherapy in metastatic gastric cancer patients who had progressed after cisplatin plus either S-1 or capecitabine

“…In terms of confirmed ORR, which is similar to the addition of cisplatin to docetaxel, the addition of S-1 to docetaxel showed a very low ORR and did not show any significant difference compared to docetaxel alone (4.3% in the D arm, 4.3% in the DC arm, and 8.7% in the DS arm; p > 0.990). Previous studies of second-line chemotherapy in MGC showed an ORR ranging from 0% to 22% [8,9,[24][25][26][27], and the ORR of the present study was much lower than the ORRs of previous studies. The small sample size might have affected the result because the baseline characteristics and treatment delivery did not appear to differ from previous studies.…”

“…In a phase III study (TCOG GI-0801/BIRIP) that compared irinotecan alone with irinotecan plus cisplatin in patients with metastatic or recurrent gastric cancer refractory to S-1-based first-line chemotherapy, the PFS (3.8 months vs. 2.8 months; hazard ratio [HR], 0.68; p=0.0398) and the DCR (75% vs. 54%, p=0.0162) were significantly better in the irinotecan plus cisplatin group than in the irinotecan alone group, whereas there was no difference in survival between the two groups [25]. In another phase III trial (TRICS), which also compared irinotecan alone with irinotecan plus cisplatin in advanced gastric cancer refractory to first-line S-1 monotherapy, the addition of cisplatin to irinotecan did not improve the PFS (4.6 months vs. 4.1 months; HR, 0.860; p=0.376) or OS (13.9 months vs. 12.7 months; HR, 0.834; p=0.288) compared to irinotecan monotherapy [26].…”

Meta-analysis of patient-level data on biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer with the TCOG GI-0801 BIRIP and ECRIN TRICS RCTs: protocol paper

“…We selected two studies, the TRICS trial 18) and the TCOG GI-0801/BIRIP trial 17) . We selected these two trials because they were randomized phase III trials employing the same regimen of biweekly CPT-11 plus CDDP versus CPT-11 alone in a second-line setting for advanced or recurrent gastric cancer.…”

“…Recently, two randomized trials employing the same regimen of biweekly CPT-11 plus CDDP versus CPT-11 alone in the second-line setting have been reported 17,18) . Higuchi et al reported (n = 130) that biweekly CPT-11 plus CDDP significantly prolonged progression free survival (PFS) (HR: 0.68) compared with CPT-11 alone, but did not demonstrate an overall survival (OS) benefit (HR: 1.00) in patients with metastatic or recurrent gastric cancer that progressed after S-1-based first-line chemotherapy 17) .…”

“…Higuchi et al reported (n = 130) that biweekly CPT-11 plus CDDP significantly prolonged progression free survival (PFS) (HR: 0.68) compared with CPT-11 alone, but did not demonstrate an overall survival (OS) benefit (HR: 1.00) in patients with metastatic or recurrent gastric cancer that progressed after S-1-based first-line chemotherapy 17) . Nishikawa et al reported (n = 168) that CPT-11/CDDP combination therapy did not show significant benefit in terms of OS (HR: 0.83) or PFS (HR: 0.86) compared with CPT-11 alone in patients with progressive AGC previously treated with S-1 monotherapy 18) . In a subset analysis confined to intestinal-type tumors, CPT-11/CDDP combination therapy was associated with significantly better OS than CPT-11 monotherapy (median OS: 15.8 months vs. 14.0 months; HR: 0.569).…”