In a pooled analysis reported in the Journal of Clinical Oncology, Gallois et al found that early discontinuation of adjuvant oxaliplatin/fluoropyrimidine regimens—consisting of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin)—was associated with poorer outcomes in patients with stage III colon cancer. Early discontinuation of oxaliplatin alone was not associated with poorer outcomes unless < 50% of planned cycles were given.
Study Details
The study used pooled data from 11 adjuvant trials in the ACCENT/IDEA database in which patients were to receive 6 months of FOLFOX (including mFOLFOX6, FOLFOX4) or CAPOX. Early discontinuation of treatment was defined as discontinuation of the entire regimen and early discontinuation of oxaliplatin as discontinuation of only oxaliplatin before 75% of planned cycles had been received. Multivariate analyses of associations of early discontinuation of treatment and early discontinuation of oxaliplatin with outcomes were adjusted for known prognostic factors, including age, sex, Eastern Cooperative Oncology Group performance status, T stage, N stage, and year of enrollment.
Key Findings
A total of 10,447 patients were evaluable for early discontinuation of treatment; of these, 2,184 (20.9%) had discontinued treatment early. A total of 7,243 were evaluable for early discontinuation of oxaliplatin; of these, 1,359 (18.8%) discontinued oxaliplatin early.
In multivariable analyses, early treatment discontinuation vs no early treatment discontinuation among all patients was associated with significantly poorer 3-year disease-free survival (69.0% vs 78.8%, hazard ratio [HR] = 1.61, P < .001) and 5-year overall survival (74.7% vs 84.7%, HR = 1.73, P < .001). By subgroup, these outcomes were significantly poorer among 7,035 patients who received FOLFOX (HR = 1.64, P < .001; HR = 1.75, P < .001) and among 3,412 who received CAPOX (HR = 1.58, P <.001; HR =1.71, P < .001).
Among all patients, early discontinuation of oxaliplatin alone vs no early oxaliplatin discontinuation was not associated with significant differences in 3-year disease-free survival (HR = 1.07, P = .3) or 5-year overall survival (HR = 1.13, P = .1). By subgroup, no significant differences in these outcomes were observed among 4,481 patients who received FOLFOX (HR = 1.00, P = 1.00; HR = 1.04, P = .6). Among 2,452 patients who received CAPOX, there was no difference in disease-free survival (HR = 1.18, P = .1); a “marginal numerical difference” was observed for 5-year overall survival (81% vs 83%, HR = 1.29, P = .02).
No significant differences in outcomes were observed among patients who received between 50% and 75% or between 75% and 100% of planned oxaliplatin cycles. Patients who received < 50% of planned cycles had significantly poorer 3-year disease-free survival (HR = 1.34, 95% confidence interval [CI] =1.10–1.64) and 5-year overall survival (HR = 1.61, 95% CI = 1.29–2.01) vs those who received 100% of cycles.
The investigators concluded: “In patients treated with 6 months of oxaliplatin-based chemotherapy for stage III [colon cancer], [early treatment discontinuation] was associated with poorer oncologic outcomes. However, this was not the case for [early oxaliplatin discontinuation]. These data favor discontinuing oxaliplatin while continuing fluoropyrimidine in individuals with significant neurotoxicity having received > 50% of the planned 6-month chemotherapy.”
Julien Taieb, MD, PhD, of Hôpital Européen Georges Pompidou, Université Paris-Cité, Paris, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
