ACHIEVE-2 Results of Oxaliplatin-Based Adjuvant Chemotherapy in Asian Patients with High-Risk Stage II Colon Cancer

The Asian researchers reported on 25 October 2020 in the Annals of Oncology that 3-month of combination therapy for adjuvant treatment of high-risk stage II colon cancer resulted with significantly less grade ≥2 peripheral sensory neuropathy (PSN) than the 6-month regimen. The 3-month regimen did not affect the 3-year disease-free survival (DFS) rate. The ACHIEVE-2 (Adjuvant Chemotherapy for colon cancer with HIgh EVidencE in high-risk stage 2) researchers concluded that a 3-month course of adjuvant CAPOX can be an option for high-risk stage II colon cancer.

Oxaliplatin-based adjuvant chemotherapy is considered an option for patients with high-risk stage II colon cancer. However, many patients develop PSN during the 6 months of oxaliplatin-based adjuvant therapy, leading to treatment modification or discontinuation. The incidence of long-lasting PSN is significantly lower with 3-month therapy than with 6-month therapy, and significantly lower with CAPOX than with mFOLFOX6.

The phase III ACHIEVE-2 study of 3 versus 6 months of mFOLFOX6/CAPOX adjuvant therapy for high-risk stage II colon cancer was conducted to assess the potential implications in reducing the adjuvant therapy duration to 3 months for Asian patients. One of the key objectives of the ACHIEVE-2 study was to provide data pertaining to Asian patients for the International Duration Evaluation of Adjuvant (IDEA) chemotherapy pooled analysis to investigate the non-inferiority of 3 versus 6 months of FOLFOX or CAPOX adjuvant chemotherapy.

The IDEA pooled analysis for high-risk stage II colorectal cancer also collected data from three other phase III trials (SCOT [UK, Denmark, Spain, Sweden, Australia, and New Zealand], TOSCA [Italy], and HORG [Greece]) to compare the therapeutic effect (non-inferiority) of 3 months versus 6 months of adjuvant treatment in patients with high-risk stage II colon cancer worldwide.

The ACHIEVE-2 was open-label, multicentre, randomised phase III study, a prospective pooled analysis conducted to investigate the non-inferiority of 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy in stage II disease. From February 2014 to 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 mFOLFOX6 or CAPOX. The primary endpoint was DFS. The secondary endpoints were treatment compliance and safety.

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. In total, 184 (36%) presented 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).

The authors concluded that a shorter duration of oxaliplatin-based adjuvant chemotherapy significantly reduced grade ≥2 PSN, and it did not compromise the DFS. However, this study was conducted as a part of the IDEA Collaboration trials and did not have the statistical power to independently determine the optimised adjuvant chemotherapy duration.

Nevertheless, the data suggested that patients with high-risk stage II colon cancer, especially patients with non-T4 and high-risk stage II colon cancer, receiving oxaliplatin-based adjuvant chemotherapy can be considered for 3 months of CAPOX therapy as a treatment option with favourable risk–benefit balance.


Yamazaki K, Yamanaka T, Shiozawa M, et al. Oxaliplatin-Based Adjuvant Chemotherapy Duration (3 vs. 6 Months) for High-Risk Stage II Colon Cancer: The Randomized Phase 3 ACHIEVE-2 Trial. Annals of Oncology; Published online 25 October 2020. DOI: