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Clinical Trial
. 2021 Jan;32(1):77-84.
doi: 10.1016/j.annonc.2020.10.480. Epub 2020 Oct 26.

Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial

K Yamazaki  1 , T Yamanaka  2 , M Shiozawa  3 , D Manaka  4 , M Kotaka  5 , M Gamoh  6 , A Shiomi  7 , A Makiyama  8 , Y Munemoto  9 , T Rikiyama  10 , M Fukunaga  11 , T Ueki  12 , K Shitara  13 , H Shinkai  14 , N Tanida  15 , E Oki  16 , E Sunami  17 , A Ohtsu  18 , Y Maehara  19 , T Yoshino  20
Affiliations
Free article
Clinical Trial

Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial

K Yamazaki et al. Ann Oncol. 2021 Jan.
Free article

Abstract

Background: Oxaliplatin-based adjuvant chemotherapy may be associated with debilitating peripheral sensory neuropathy (PSN) in patients with high-risk stage II colon cancer. This open-label, multicenter, randomized phase III trial was conducted as a prospective pooled analysis to investigate the non-inferiority of 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy.

Patients and methods: From 12 February 2014 to 31 January 2017, 525 Asian patients with high-risk stage II colon cancer were randomly assigned to 3- and 6-month treatment arms. The treatment consisted of either modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine combined with oxaliplatin (CAPOX). The primary end point was disease-free survival (DFS). The secondary end points were treatment compliance and safety.

Results: Of the 525 randomized patients, 11 were not treated. Among the 514 participating patients (255 in the 3-month arm; 259 in the 6-month arm), 432 (84%) received CAPOX, and 184 (36%) presented with T4 as a high-risk factor for recurrence. The 3-year DFS rate was 88.2% in the 3-month arm and 87.9% in the 6-month arm [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.67-1.87]. With CAPOX, the 3-year DFS rate was 88.2% in the 3-month arm and 88.4% in the 6-month arm (HR, 1.13; 95% CI, 0.65-1.96). The discontinuation rate in the 3- and 6-month arms was 10% and 31% for mFOLFOX6 (P = 0.0193), and 15% and 35% for CAPOX (P < 0.0001), respectively. The incidence of grade ≥2 PSN was significantly lower in the 3-month arm than in the 6-month arm (16% and 43%, respectively, P < 0.0001).

Conclusions: Three months of combination therapy presented significantly less grade ≥2 PSN than the respective 6-month regimen. The shortened therapy duration did not affect the 3-year DFS rate, suggesting that a 3-month course of CAPOX can be an effective treatment option.

Clinical trial information: UMIN Clinical Trials Registry, UMIN000013036 and Japan Registry of Clinical Trials, jRCTs031180128.

Keywords: adjuvant chemotherapy; high-risk stage II colon cancer; oxaliplatin; treatment duration.

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Conflict of interest statement

Disclosure KY reports the receipt of honoraria from Chugai, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho, Lilly, Sanofi, ONO, MSD, and Bristol-Myers Squibb. TY reports the receipt of honoraria from Chugai, Takeda, Taiho, Boehringer Ingelheim, Bayer, and Pfizer; fees for consultancy from Gilead Sciences, Daiichi Sankyo, HUYA Biosciences, and Sysmex; and research funding from Chugai, Takeda, Taiho, Daiichi Sankyo, ONO, Boehringer Ingelheim, Bayer, Merck Serono, Astellas, and Eli Lilly. MK reports the receipt of honoraria from Chugai, Yakult Honsha, and Takeda. AM reports the receipt of honoraria from Lily, Chugai, and Takeda. KS reports the receipt of fees for consultancy from Astellas, Lilly, Bristol-Myers Squibb, Takeda, Pfizer, Ono, Novartis, AbbVie, Taiho, MSD, and GlaxoSmithKline; honoraria from Novartis, AbbVie, and Yakult Honsha; and research funding from Astellas, Lilly, ONO, Sumitomo Dainippon, Daiichi Sankyo, Taiho, Chugai, and Medi-Science. EO reports the receipt of lecture fees from Yakult Honsha, Taiho, Takeda, Chugai, Eli Lilly, and Bayer. AO reports the receipt of honoraria from BMS, ONO, Taiho, and Chugai; and research funding from BMS. TY reports the receipt of research funding from Novartis, MSD, Sumitomo Dainippon, Chugai, Sanofi, Daiichi Sankyo, PAREXEL, ONO, and GlaxoSmithKline. The remaining authors have declared no conflicts of interest.

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