Post-recurrent survival of a phase III trial comparing adjuvant chemotherapy with docetaxel plus S-1 versus S-1 alone in stage III gastric cancer: A post-hoc analysis of the START-2 trial (JACCRO GC-07).
Authors: Ishida Hiroo , Sunakawa Yu , Kodera Yasuhiro , Yoshida Kazuhiro , Kochi Mitsugu , Kakeji Yoshihiro , Sano Takeshi , Takeuchi Masahiro , Ichikawa Wataru , Fujii Masashi 
Published: January 2023

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Background: The START-2 trial showed docetaxel plus S-1 (DS) was superior to S-1 alone (S-1) in terms of recurrence-free survival (RFS) and overall survival (OS) as the adjuvant chemotherapy for stage III gastric cancer patients (pts) (J Clin Oncol 2019, Gastric Cancer 2022). However, the optimal treatment strategy has been controversial for pts who develop recurrence after DS. Methods: We investigated the post-recurrence survival (PRS) of pts who developed recurrence during and after adjuvant chemotherapy using the results of the START-2. The PRS was analyzed according to time to recurrence or treatment regimens. Also, survival rates were estimated by the Kaplan-Meier methods. A cox proportional hazards model was used to calculate hazard ratio (HR). The PRS was defined as the interval from the date of recurrence to the date of death from any cause. Results: A total of 361 pts had confirmed recurrence (154 of 441 pts in the DS group and 207 of 452 pts in the S-1 group). In pts with recurrence, 109 of 154 pts in the DS group and 156 of 207 pts in the S-1 group received chemotherapy. Median PRS were 12.9 months (mo) (95% confidence interval [CI] 10.7-16.7) in the DS group and 13.5 mo (95% CI 10.7-16.2) in the S-1 group (HR 1.09, 95% CI 0.83-1.44, p = 0.52). In the DS group and S-1 group, 69 and 95 pts received platinum-based (cisplatin or oxaliplatin) regimen, 25 and 44 received taxane (paclitaxel or docetaxel), 14 and 17 received other regimens (such as fluoropyrimidine monotherapy or irinotecan), respectively. Median PRS was significantly longer in pts who received platinum-based regimen compared with non-platinum regimen in the DS group (p = 0.0039), whereas there was no significant difference in the S-1 group (p = 0.07). In comparison of PRS between pts treated with platinum-based regimen and taxane-based one, HR was 0.46 (95% CI, 0.28-0.76, p=0.0019) in the DS group and 0.69 (95% CI, 0.47-1.02, p=0.063) and the S-1 group. In pts with recurrence during or less than 6 mo from completion of DS, median PRS was significantly longer in pts who received platinum- based regimen compared to taxane-based one. Whereas, there was no statistically significance in the PRS between the 2 regimens for recurrence in pts with recurrence during or less than 6 mo from completion of S-1. Among pts with recurrence after 6 mo or later, median PRS was favorable in pts treated with platinum-based regimen in both DS and S-1 group although no statistical significance. Conclusions: The addition of docetaxel to S-1 in adjuvant treatment of stage III gastric cancer did not affect PRS. Platinum-based chemotherapy might be a favorable choice for pts with recurrence during or after completion of docetaxel plus S-1 as adjuvant chemotherapy, especially in pts with a RFS of less than 6mo. Further prospective studies are warranted to validate these findings. Clinical trial information: UMIN000010337 .