Practice Patterns and Health Outcomes of Adjuvant Oxaliplatin Chemotherapy for Colorectal Cancer

INTRODUCTION: Oxaliplatin-containing adjuvant chemotherapy improves survival for stage III colon cancer. Yet it is not without harms, most commonly dose-dependent peripheral neuropathy. The 2018 International Duration Evaluation of Adjuvant Chemotherapy (IDEA) trial sought to determine the optimal duration of adjuvant therapy by evaluating the non-inferiority (NI) of 3 versus 6 months of treatment. The 3-year disease-free survival probability was 74.6% in the 3-month group versus 75.5% in the 6-month group (HR 1.07, 95% CI 1.00-1.15; pNI = 0.11). There remain open questions regarding how these findings changed practice, whether these outcomes are obtained in the general population, and – given oxaliplatin-induced neuropathy – the relationship between treatment duration and post-treatment falls. METHODS: We leveraged linked administrative and population-based datasets held at ICES to conduct three retrospective cohort studies of patients with stage III colon cancer in Ontario, Canada. First, we employed interrupted time series regression and mixed models to evaluate the association between IDEA’s publication and prescribed treatment durations. Second, we utilized overlap propensity score-weighted survival models to determine the relationship between treatment duration and mortality. Third, we again used weighted survival models to examine the association between treatment duration and fall-related injury. RESULTS: IDEA’s publication was associated with a 16.4% (95% CI 12.5-20.3%) absolute increase in patients treated with ≤50% of a 6-month course of therapy. Between-prescriber variation strongly influenced treatment duration in the post-IDEA period (median odds ratio 2.10 [95% CI 1.73-3.18] for short-duration treatment). Treatment with 50% of a 6-month course of therapy was associated with a HR of 1.13 (95% CI 0.88-1.47) for overall mortality versus >85% of a 6-month course of therapy. Meanwhile, treatment with >85% of a 6-month course of therapy conferred a HR of 0.84 (95% CI 0.62-1.13) for fall-related injury. CONCLUSION: Although IDEA could not conclude non-inferiority of 3 to 6 months of adjuvant therapy, the trial rapidly shifted clinical practice while introducing greater provider-level practice variation. While intuitive concerns about the relationship between oxaliplatin and fall-related injury are not borne out in the data, evidence from routine practice solidifies that treatment duration is a preference-sensitive decision involving a tradeoff between survival and toxicity.

Department dc:contributor.department

Dalla Lana School of Public Health

Year dc:date.issued

2023

Author dc:creator

• Sue-Chue-Lam, Colin James

Advisor dc:contributor.advisor

• Baxter, Nancy N

• chemotherapy
• colorectal cancer
• neuropathy
• non-inferiority
• oxaliplatin
• practice variation

Statement dc:rights

• Attribution-NonCommercial-ShareAlike 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-sa/4.0/

Handle dc:identifier.uri

http://hdl.handle.net/1807/129808

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/129808