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

AimThe optimal second-line regimen for treating advanced gastric cancer (AGC) remains unclear. While irinotecan (CPT-11) plus cisplatin (CDDP) combination therapy and CPT-11 monotherapy have been explored in the second-line setting, the superiority of second-line platinum-based therapies for AGC patients initially treated with S-1 monotherapy has not yet been evaluated; therefore, we aimed to examine the survival benefit of CPT-11/CDDP combination over CPT-11 monotherapy. MethodsAGC patients showing progression after S-1 monotherapy for advanced cancer or recurrence within 6months after completion of S-1 adjuvant therapy were randomly allocated to CPT-11/CDDP (CPT-11, 60mg/m2; CDDP, 30mg/m2, q2w) or CPT-11 (150mg/m2, q2w). ResultsSixty-eight advanced and 95 recurrent cases were evaluated. The median overall survivals were 13.9 (95% confidence interval [CI]: 10.8–17.6) and 12.7 (95% CI: 10.3–17.2) months for CPT-11/CDDP and CPT-11, respectively (hazard ratio: 0.834; 95% CI: 0.596–1.167, P=0.288). No significant differences were observed in the secondary end-points, including progression-free survival (4.6 [95% CI: 3.4–5.9] versus 4.1 [95% CI: 3.3–4.9]months) and response rate (16.9% [95% CI: 8.8–28.3] versus 15.4% [95% CI: 7.6–26.5]). The incidences of grade 3–4 anaemia (16% versus 4%) and elevated serum lactate dehydrogenase levels (5% versus 0%) were higher for CPT-11/CDDP than for CPT-11. Exploratory subgroup analysis revealed that CPT-11/CDDP was significantly more effective for intestinal-type AGC, compared with CPT-11 (overall survival: 15.8 versus 14.0months; P=0.019). ConclusionNo survival benefit was observed upon adding CDDP to CPT-11 after S-1 monotherapy failure.