Results of a randomized phase 3 trial demonstrated that the 3-month regimen of adjuvant combination therapy caused significantly less grade 2 or more peripheral sensory neuropathy than the 6-month regimen as treatment of patients with high-risk stage II colorectal cancer, while not affecting the 3-year disease-free survival rate, according to a report in the Annals of Oncology.
Results of a randomized phase 3 trial demonstrated that the 3-month regimen of adjuvant combination therapy caused significantly less grade 2 or more peripheral sensory neuropathy (PSN) than the 6-month regimen as treatment of patients with high-risk stage II colorectal cancer (CRC), while not affecting the 3-year disease-free survival (DFS) rate, according to a report in the Annals of Oncology.1
The ACHIEVE-2, or the Adjuvant Chemotherapy for colon cancer with HIgh EVidencE in high-risk stage 2, study [UMIN000013036] investigated CAPOX (capecitabine and oxaliplatin) or mFOLFOX6 (modified fluorouracil, leucovorin, and oxaliplatin) given for 3 months versus 6 months for noninferiority in a prospective pooled analysis.
Of the 514 eligible patients, including 255 in the 3-month arm and 259 in the 6-month arm, 432 (84%) were given CAPOX and 82 (16%) had mFOLFOX6. Overall, there was a 3-year DFS rate of 88.2% for the 3-month regimen and 87.9% for the 6-month regimen (HR, 1.12; 95% CI, 0.67-1.87). Patients who received CAPOX had a DFS rate of 88.2% and 88.4% for the 3- and 6-month arms at 3 years, respectively (HR 1.13; 95% CI, 0.65-1.96).
Ten percent of patients in the 3-month arm and 31% in the 6-month arm discontinued mFOLFOX6 (P =.0193), and 15% in the 3-month arm and 35% in the 6-month arm discontinued CAPOX (P <.0001.)
In patients on the 3-month regimen, the incidence of grade 2 or more PSN was significantly lower than for those on the 6-month regimen, at 16% and 43%, respectively (P <.0001). PSN is associated with oxaliplatin-based adjuvant chemotherapy in patients with high-risk stage II CRC.
The initial publication of this trial from 2019 showed significantly less grade 3 to 5 toxicity with the 3-month treatment (P =.0003). The grade 2 or higher neurotoxicity was also significantly lower in the 3-month arm compared with the 6-month arm, at 16.5% and 42.9%, respectively (P <.0001). This was the same for grade 3 or higher neurotoxicity at 0.8% and 6.9% (P =.0003).2
Additionally, the first publication identified multiple high-risk features for recurrence in these patients: 87.5% of patients presented with vascular invasion, 35.8% with T4, 19.3% with obstruction, 12.8% with inadequate nodal harvest, 11.5% with poorly differentiated, and 6.4% with perforation.
In this open-label, multicenter, randomized phase 3 trial, 525 Asian patients were enrolled from February 2014 to January 2017, although 11 were not treated. The primary end point was DFS, and secondary end points included treatment compliance and safety.
“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,” the investigators concluded in their report.1
1. 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. Ann Oncol. Published online October 25, 2020. Accessed October 29, 2020. doi:10.1016/j.annonc.2020.10.480
2. Yoshino T, Yamanaka T, Shiozawa M, et al. 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). Ann Oncol. 2019;30(suppl 5):V199. doi:10.1093/annonc/mdz246.003