Trends and Prescriber Variation in the Duration of Oxaliplatin-Containing Adjuvant Chemotherapy for Stage III Colon Cancer From 2007 to 2019: A Population-Based Retrospective Cohort Study.

INTRODUCTION: The International Duration Evaluation of Adjuvant Therapy (IDEA) collaboration in 2017 established 3 months of adjuvant therapy as an alternative to 6 months of therapy for stage III colon cancer. We determined the association between the IDEA publication, changes in clinical practice, and prescriber variation. PATIENTS AND METHODS: Using linked databases, we identified Ontarians aged ≥18 years at diagnosis of stage III colon cancer between 2007 and 2019 who received oxaliplatin-containing adjuvant therapy. The outcome was duration of therapy, categorized as ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% of a 6-month course of therapy to approximate treatment durations in the IDEA collaboration. We examined trends in duration over time using an interrupted time series regression model. We analyzed treatment duration after accounting for patient and prescriber characteristics, using multivariable mixed effects logistic regression models to quantify between-prescriber variation. RESULTS: We included 4695 patients with stage III colon cancer who received oxaliplatin-containing adjuvant chemotherapy, of whom 77.5% initiated treatment pre-IDEA and 22.5% initiated treatment post-IDEA. Post-IDEA, there was a 16.4% (95% CI, 12.5%-20.3%) absolute increase in the proportion of patients treated with ≤50% of a maximal course of therapy. This trend was greatest among patients with low-risk tumors. Prescriber variation increased pre-IDEA to 15.6% post-IDEA (variance partition coefficient 5.4% pre-IDEA and 15.6% post-IDEA). CONCLUSION: The publication of IDEA was associated with increases in short duration adjuvant therapy and prescriber-level practice variation for stage III colon cancer. Clinicians should be better supported to make consistent recommendations about adjuvant duration under conditions of uncertainty and trade-offs.

The Association of Oxaliplatin-Containing Adjuvant Chemotherapy Duration with Overall and Cancer-Specific Mortality in Individuals with Stage III Colon Cancer: A Population-Based Retrospective Cohort Study.

PURPOSE: Few studies have examined the relationship between duration of oxaliplatin-containing adjuvant chemotherapy for stage III colon cancer and mortality in routine practice. We examined the association between treatment with 50% versus >85% of a maximal course of adjuvant therapy (eight cycles of CAPOX, twelve cycles of FOLFOX) and mortality in stage III colon cancer. METHODS: Using linked databases, we identified Ontarians aged ≥18 years at diagnosis of stage III colon cancer between 2007 and 2019. In the primary comparison, we compared patients who received 50% or >85% of a maximal course of adjuvant therapy; in a secondary comparison, we evaluated a dose effect across patients who received FOLFOX in one-cycle increments from six to ten cycles against >85% (more than ten cycles) of a maximal course of FOLFOX. The main outcomes were overall and cancer-specific mortality. Follow-up began 270 days after adjuvant treatment initiation and terminated at the first of the outcome of interest, loss of eligibility for Ontario's Health Insurance Program, or study end. Overlap propensity score weights accounted for baseline between-group differences. We determined the hazard ratio, estimating the association between mortality and treatment. Non-inferiority was concluded in the primary comparison for either outcome if the upper limit of the two-sided 95% CI was ≤1.11, which is the margin used in the International Duration Evaluation of Adjuvant Chemotherapy Collaboration. RESULTS: We included 3546 patients in the analysis of overall mortality; 486 (13.7%) received 50% and 3060 (86.3%) received >85% of a maximal course of therapy. Median follow-up was 5.4 years, and total follow-up was 20,510 person-years. There were 833 deaths. Treatment with 50% of a maximal course of adjuvant therapy was associated with a hazard ratio of 1.13 (95% CI 0.88 to 1.47) for overall mortality and a subdistribution hazard ratio of 1.31 (95% CI 0.91 to 1.87) for cancer-specific mortality versus >85% of a maximal course of therapy. In the secondary comparison, there was a trend toward higher overall mortality in patients treated with shorter durations of therapy, though confidence intervals overlapped considerably. CONCLUSION: We could not conclude that treatment with 50% of a maximal course is non-inferior to >85% of a maximal course of adjuvant therapy for mortality in stage III colon cancer. Clinicians and patients engaging in decision-making around treatment duration in this context should carefully consider the trade-off between treatment effectiveness and adverse effects of treatment.