Dr. Thierry André presents Abstract 3500.
“A reduction of adjuvant treatment for stage III colon cancer may decrease toxicities without loss of efficacy and could provide clear advantages to patients and health care providers,” Thierry André, MD, of Hôpital Saint-Antoine, in France, said, during an Oral Abstract Session on June 5.
The trial he presented was one of six included in the IDEA collaboration, which was presented during the Plenary Session on June 4 (Abstract LBA1). It found that, although 3 months of chemotherapy is not noninferior to 6 months in the overall cohort of patients with stage III colon cancer, there may be differences that are based on the oxaliplatin regimen chosen, and the toxicity of the longer chemotherapy course may make the 3-month option more favorable in certain patients.
The IDEA France study presented by Dr. André included 2,010 patients, randomly assigned to either 3 or 6 months of oxaliplatin-containing regimens (modified FOLFOX6 [mFOLFOX6; fluorouracil, leucovorin, and oxaliplatin] or CAPOX [capecitabine and oxaliplatin] by physician’s choice). Patients had a median age of 64, and almost all had an Eastern Cooperative Oncology Group performance status of either 0 (74%) or 1 (25%). Most patients (90%) received mFOLFOX6 (90%). Patient characteristics were well balanced between the 3-month and 6-month arms.
The mean chemotherapy duration for patients in the 3-month arm was 11.8 weeks compared with 21.7 weeks for patients in the 6-month arm. A total of 94% of patients in the 3-month arm received their assigned full length of chemotherapy treatment compared with 78% of patients in the 6-month arm.
After a median follow-up of 4.3 years, the patients in the 6-month arm had a 3-year DFS rate of approximately 72% compared with approximately 76% of patients in the 6-month arm, which yielded a hazard ratio (HR) of 1.24 (95% CI [1.05, 1.46]; p = 0.011). Exploratory subgroup analyses suggested that the 6-month course of therapy may offer greater benefit in T4 or N2 disease, and there was a stronger effect with mFOLFOX6 than with CAPOX.
Specifically, in the 1,809 patients on the mFOLFOX6 regimen, the 3-year DFS rate was 72% with 3 months of therapy, and it was 76% with 6 months (HR 1.27, 95% CI [1.07, 1.51]). For patients treated with this regimen who had T4 or N2 disease, the HR was 1.44 (95% CI [1.14, 1.82]).
Not surprisingly, the 6-month chemotherapy regimen yielded more adverse events; 46.4% of those patients experienced a grade 3 or higher event compared with 29.5% of the patients in the 3-month arm (p < 0.001). Grade 3 or higher neutropenia, thrombocytopenia, fatigue, and oxaliplatin allergy (of grade 2 or higher) were all significantly increased with the 6-month course of chemotherapy.
The rate of grade 2 peripheral neuropathy was 38.6% in the patients in the 6-month arm during the first 7 months after treatment. For the patients in the 3-month arm, the rate was 23.5%. For grade 3/4 neuropathy during the first 7 months, the rates were 20.5% in the patients on the 6-month treatment and 5.9% in the patients on the 3-month regimen (p < 0.001).
Importantly, neuropathy can persist after treatment is completed. A total of 5.8% of patients in the 6-month arm had grade 2 residual neuropathy on their last follow-up visit compared with 2.3% of patients in 3-month arm. Grade 3/4 rates at that visit were 1.6% in the 6-month arm and 0.5% in the 3-month (p < 0.001).
“This study, with 90% of patients treated with mFOLFOX6, shows that 6 months adjuvant chemotherapy is superior to 3 months,” Dr. André said.
However, the DFS advantage for patients with T1-3N1 disease was small, so it must be balanced with the higher sensory neuropathy rates. For the patients with T4 or N2 disease, he said, the larger DFS advantage suggests that those patients should maintain chemotherapy for the full 6 months unless grade 2 or higher neuropathy is present.
“Ultimately, we may have to believe that the difference between [the IDEA trials] was the percent of CAPOX versus FOLFOX,” the discussant for the session, Jeffrey A. Meyerhardt, MD, MPH, FASCO, of the Dana-Farber Cancer Institute, said. He pointed out that the IDEA France trial had far higher rates of FOLFOX use than others included in the collaboration.