401MO - OS and long-term DFS with 3- vs. 6-month adjuvant oxaliplatin and fluoropyrimidine-based therapy for stage III colon cancer patients: A randomized phase III ACHIEVE trial

Background

Pooled analysis of International Duration Evaluation of Adjuvant therapy (IDEA) did not demonstrate the non-inferiority of 3- vs. 6-month (m) adjuvant FOLFOX/CAPOX for disease-free survival (DFS) in stage III colon cancer (CC) patients. However, in patients treated with CAPOX (especially low-risk patients), 3-m therapy had similar efficacy as the 6-m one. Herein, we report the overall survival (OS) and long-term DFS for the ACHIEVE trial, as part of the IDEA collaboration.

Methods

ACHIEVE was a randomized, open-label, multicenter study that allocated stage III CC patients to 3-m or 6-m mFOLFOX6/CAPOX post-surgery. Hazard ratios (HRs) for the association between survival endpoints and treatment duration (3 m or 6 m) were analyzed using the Cox model. Pre-planned confirmatory sub-group analyses included regimens and risk groups.

Results

As of September 2019, 175 deaths and 323 DFS events were observed in the modified intention-to-treat population (n=1,291), with an overall median survival follow-up of 62 m. Seventy-five percent of the patients received CAPOX. Fifty-six percent were low-risk (T1-3 and N1), while 44% were high-risk (T4 or N2). The 5-yr OS rate was 87% (95% confidence interval [CI], 84–90%) and 87% (84–89%) in the 3-m and 6-m therapy groups, respectively, with an estimated HR of 0.90 (0.67–1.21). The 5-year DFS rate was 75% (72–78%) and 74% (71–78%) in the 3- and 6-m therapy groups, respectively, with an estimated HR of 0.94 (0.76–1.18). For the HRs (95% CI) in the pre-planned subgroup analyses, please refer to the table. Table: 401MO

Conclusions

Our data indicate that previous heterogeneous DFS results based on regimens and risk groups became almost the same; the OS and DFS of 3-m and 6-m groups were comparable. Three-month adjuvant CAPOX therapy could be used for most stage III CC patients, but our results should be interpreted in the context of the whole IDEA collaboration.

Clinical trial identification

UMIN000008543.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

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.; Honoraria (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.; Research grant/Funding (institution): GlaxoSmithKline K.K.. M. Kotaka: Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Yakult Honsha; Honoraria (self): Takeda Pharmaceutical. M. Nakamura: Speaker Bureau/Expert testimony: Chugai Co.Ltd.; Speaker Bureau/Expert testimony: Yakult Honsya Co. Ltd.. T. Kato: Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd; Honoraria (self): Takeda Pharmaceutical Company Limited; Honoraria (self): Eli Lilly; Honoraria (self): Bayer Yakuhin; Honoraria (self): Sanofi; Honoraria (self): Yakult Honsha. T. Mizushima: Speaker Bureau/Expert testimony: EA Pharma Co., Ltd.; Speaker Bureau/Expert testimony: AbbVie GK.; Speaker Bureau/Expert testimony: Miyarisan Pharmaceutical Co. Ltd.; Speaker Bureau/Expert testimony: Janssen Pharmaceutical K.K; Speaker Bureau/Expert testimony: Kyorin Pharmaceutical Co., Ltd.; Speaker Bureau/Expert testimony: Daiichi Sankyo Company, Limited.; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Mitsubishi Tanabe Pharma Corporation; Speaker Bureau/Expert testimony: Takeda Pharmaceutical Company Limited; Research grant/Funding (institution): Taiho Pharmaceutical Co., Ltd.; Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Research grant/Funding (institution): Sanofi K.K.; Research grant/Funding (institution): Astellas Pharma Inc.; Research grant/Funding (institution): Shionogi & 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: Huya Biosciences; Advisory/Consultancy: Sysmex; Research grant/Funding (institution): Ono; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Eli Lilly. A. Ohtsu: Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self): Ono; Honoraria (self): Taiho; Honoraria (self): Chugai. All other authors have declared no conflicts of interest.