2274 - ACHIEVE-2 trial: a randomized phase III trial investigating duration of adjuvant (adj) oxaliplatin-based therapy (3 vs 6 months) for patients (pts) with high-risk stage II colon cancer (CC)

Background

The IDEA collaboration, a prospective pooled analysis of four concurrently conducted randomized phase III trials (SCOT, TOSCA, ACHIEVE-2, and HORG) for pts with high-risk stage II CC investigating duration of adj oxaliplatin-based therapy, were presented at ASCO 2019. The results of ACHIEVE-2 trial, the only investigation in Asia, are presented here.

Methods

ACHIEVE-2 was an open-label, multicenter trial randomizing pts with high-risk stage II CC (T4, inadequate nodal harvest, poorly differentiated, obstruction, perforation or vascular invasion) to receive 3 months (m) or 6m of mFOLFOX6/CAPOX after curative surgery. Choice of regimen was declared before randomization by a site investigator. Primary endpoint was disease-free survival (DFS). No formal hypothesis testing for non-inferiority (NI) was planned in this trial.

Results

Between Feb 2014 and Jan 2017, 525 pts were randomized. The primary analysis included 514 randomized pts of which 82 had mFOLFOX6 (16.0%) and 432 had CAPOX (84.0%). High-risk features included 35.8% of T4, 12.8% of inadequate nodal harvest, 11.5% of poorly differentiated, 19.3% of obstruction, 6.4% of perforation and 87.5% of vascular invasion. There was significantly less grade 3-5 toxicity with 3m treatment (p = 0.0003). Grade 2 or higher neurotoxicity in 3m was significantly lower than that in 6m (16.5% vs. 42.9%, p < 0.0001), and the same was observed for grade 3 or higher neurotoxicity (0.8% vs. 6.9%, p = 0.0003). As of Mar 2019, 60 DFS events were observed with a median follow-up of 36 m. The 3-year DFS rate was 88.2% for 3m and 87.9% for 6m, with a hazard ratio (HR) of 1.12 (95% CI, 0.67-1.87; p for NI = 0.3942). For CAPOX the HR was 1.13 (95% CI, 0.65-1.96; p for NI = 0.4139) and for mFOLFOX6 the HR was 1.08 (95% CI, 0.26-4.42; p for NI = 0.4404).

Conclusions

Shorter duration significantly decreased overall toxicities including neurotoxicity. Our results need to be interpreted within the IDEA combined analysis as well as in terms of the reproducibility of results across all trials.

Clinical trial identification

UMIN000013036.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Japanese Foundation for Multidisciplinary Treatment of Cancer under the contract with Yakult Honsha.

Disclosure

T. Yoshino: Research grant / Funding (institution): Novartis Pharma K.K; Research grant / Funding (institution): MSD.K.K.; Research grant / Funding (institution): Sumitomo Dainippon Pharma Co., Ltd.; Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Research grant / Funding (institution): Sanofi K.K.; Research grant / Funding (institution): Daiichi Sankyo Company, Limited; Research grant / Funding (institution): Parexel International Inc.; Research grant / Funding (institution): Ono Pharmaceutical Co., Ltd. T. Yamanaka: Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Research grant / Funding (institution): Boehringer-Ingelheim; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): Pfizer; Advisory / Consultancy: Gilead Sciences; Advisory / Consultancy, Research grant / Funding (institution): Daiichi-Sankyo; Advisory / Consultancy: Sysmex; Advisory / Consultancy: Huya Biosciences; Research grant / Funding (institution): Ono; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Eli Lilly. M. Kotaka: Honoraria (self): Yakult Honsha; Honoraria (self): Chugai pharmaceutical. M. Gamoh: Honoraria (self): Taiho; Honoraria (self): Bayer; Honoraria (self): Novartis; Honoraria (self): Ono; Honoraria (self): Shionogi; Honoraria (self): Sanofi; Honoraria (self): Asahikasei; Honoraria (self): Chugai; Honoraria (self): Takeda; Honoraria (self): Daiichisankyo; Honoraria (self): Merck; Honoraria (self): Nipponkayaku; Honoraria (self): Eli Lilly Japan. A. Makiyama: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lily Pharmaceutical; Speaker Bureau / Expert testimony: Chugai; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Takeda. K. Shitara: Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Ono; Advisory / Consultancy, Research grant / Funding (institution): MSD; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Medi Science; Honoraria (self): Novartis; Honoraria (self): AbbVie; Honoraria (self): Yakult. K. Yamazaki: Speaker Bureau / Expert testimony: Chugai; Speaker Bureau / Expert testimony: Yakult. A. Ohtsu: Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self): Chugai; Honoraria (self): Taiho; Honoraria (self): Ono; Honoraria (self): Eisai. Y. Maehara: Research grant / Funding (institution): Yakult; Research grant / Funding (institution): Chugai. All other authors have declared no conflicts of interest.