A randomized phase III trial comparing primary tumor resection plus chemotherapy with chemotherapy alone in incurable stage IV colorectal cancer: JCOG1007 study (iPACS).
Yukihide Kanemitsu, Kohei Shitara, Junki Mizusawa, Tetsuya Hamaguchi, Dai Shida, Koji Komori, Satoshi Ikeda, Hitoshi Ojima, Seiji Hasegawa, Akio Shiomi, Jun Watanabe, Yasumasa Takii, Takashi Yamaguchi, Kenji Katsumata, Masaaki Ito, Jyunji Okuda, Ryoji Hyakudomi, Yasuhiro Shimada, Hiroshi Katayama, Haruhiko Fukuda
Abstract
7 Background: It is still controversial whether primary tumor resection (PTR) before chemotherapy (CTX) improves overall survival (OS) of colorectal cancer (CRC) patients (pts) with synchronous unresectable metastases. There are several retrospective analyses suggesting better outcomes in pts who underwent PTR compared to pts without it, but no prospective studies confirming these results. We conducted a randomized controlled trial to confirm the superiority of PTR plus CTX to CTX alone in asymptomatic unresectable stage IV CRC patients. Methods: Eligibility criteria included histologically proven colon and upper rectal adenocarcinoma, cT1-4 without involvement of other organs, presence of three or less unresectable factors confined to either liver, lungs, distant lymph nodes, or peritoneum, aged 20-74, no symptoms due to primary tumor and PS 0-1. Eligible patients were randomized to either PTR followed by CTX or CTX alone. CTX regimens were declared before study entry; options included mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab. The primary endpoint was the OS. The planned sample size was 140 pts per arm, with one-sided alpha of 5%, and 70% power detecting a median OS difference of 8 months (24 months vs. 32 months). Results: Between Jun 2012 and Apr 2019, 160 patients were randomized. 78 pts were allocated to PTR plus CTX, and 82 pts to CTX alone. When the first interim analysis was performed in Sep 2019, with 50% (114/227) of the expected events observed, the DSMC recommended the early termination of the trial based on its futility. With a median follow-up period of 22.0 months for 160 patients, median OS was25.9 months (95% CI 19.9 – 31.5) with PTR plus CTX and 26.7(21.9 – 32.5) with CTX alone (hazard ratio 1.10 [0.76 – 1.59], one-sided p = 0.69). Median PFS was 10.4 (8.6-13.4) with PTR plus CTX and 12.1 (9.4 – 13.2) with CTX alone (hazard ratio 1.08 [0.77 – 1.50]). There were three treatment related deaths following PTR due to postoperative complications. Conclusions: PTR followed by CTX has no survival benefit over CTX alone. PTR is not recommended for CRC patients with asymptomatic primary tumor and synchronous unresectable metastases. Clinical trial information: UMIN000008147.