New Results Released from the ACHIEVE Study

 A 3-month course of capecitabine plus oxaliplatin (CAPOX) may be the most appropriate course of treatment to reduce the rate of peripheral sensory neuropathy (PSN) in patients with stage III colon cancer, according to results of the ACHIEVE study out of Japan.

Disease-free survival was improved among patients receiving a 3-month course of oxaliplatin-based chemotherapy compared with a 6-month course. It was also improved among those who received CAPOX compared with those who received modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6), according to results of the study.

ACHIEVE is one of six studies that are part of the International Duration Evaluation of Adjuvant (IDEA) chemotherapy collaboration, a global collaborative effort to evaluate the noninferiority of 3-month vs 6-month oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer using a prospectively designed, pooled analysis of 6 concurrently conducted phase III randomized trials.  It was the only study conducted with Asian patients.

“Since the shortened therapy duration did not compromise outcomes, 3 months of CAPOX therapy might be the most appropriate treatment option, especially in patients with low-risk stage III colon cancer,” Takayuki Yoshino, MD, PhD, of National Cancer Center Hospital East, Kashiwa, Japan, and colleagues wrote in JAMA Oncology. “Although our results need to be interpreted within the IDEA combined analysis as well as in terms of the reproducibility of results across trials.”

ACHIEVE included 1,313 patients with stage III colon cancer. Patients were randomly assigned to 3 or 6 months of adjuvant chemotherapy chosen by the treating physician. Ultimately, 1,291 patients initiated treatment; 650 received 3 months and 641 received 6 months. The majority of patients (75%) underwent chemotherapy with CAPOX.

The 3-year disease-free survival for patients in the 3-month arm was 79.5% compared with 77.9% for the 6-month arm. The hazard ratio for the 3-month arm compared with the 6-month arm was 0.95 (95% CI, 0.76–1.20).

“Although this study did not define a noninferiority margin, the upper limit of the 95% CI exceeds the upper limit of 1.12 for noninferiority set by the IDEA Collaboration,” the researchers wrote.

Three-year disease-free survival for 3 months of mFOLFOX6 was 73.9% compared with 72.3% for 6 months of treatment. Three-year disease-free survival for 3 months of CAPOX was 81.4% compared with 79.7% for 6 months of CAPOX.

The rate of any grade PSN lasting 3 years was more than doubled in the 6-month arm compared with the 3-month arm (9.7% vs 24.3%; P<.001). PSN lasting for 3 years was significantly lower for patients treated with CAPOX compared with mFOLFOX6 in both the 3-month (7.9% vs 15.7%; P=.04) and 6-month arms (21.0% vs 34.1%; P=.02).

“Although our exploratory analysis requires confirmation of the reproducibility of the results as part of the IDEA Collaboration as well as in a prospective randomized comparison, this is the first evidence that FOLFOX may be a more neurotoxic chemotherapy drug than CAPOX in terms of long-term PSN, despite comparable cumulative oxaliplatin doses,” the researchers wrote.