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Multicenter Study
. 2021 Mar 1;4(3):e213587.
doi: 10.1001/jamanetworkopen.2021.3587.

Association of a Shortened Duration of Adjuvant Chemotherapy With Overall Survival Among Individuals With Stage III Colon Cancer

Devon J Boyne  1   2   3   4 , Winson Y Cheung  1   2   5 , Robert J Hilsden  3   5 , Tolulope T Sajobi  3 , Atul Batra  2 , Christine M Friedenreich  2   3   4 , Darren R Brenner  1   2   3   4
Affiliations
Multicenter Study

Association of a Shortened Duration of Adjuvant Chemotherapy With Overall Survival Among Individuals With Stage III Colon Cancer

Devon J Boyne et al. JAMA Netw Open. .

Abstract

Importance: Several real-world oncology studies have produced findings that contradict those from randomized clinical trials. Such disparities may be associated with methodological shortcomings.

Objective: To examine the association between a shortened duration of adjuvant chemotherapy among individuals with stage III colon cancer using real-world data.

Design, setting, and participants: This comparative effectiveness study included individuals diagnosed with stage III colon cancer between January 2004 and December 2015 who initiated adjuvant chemotherapy at oncology clinics within the province of Alberta, Canada. Patients were identified through record linkage of various administrative databases and were followed up until September 2017. Eligibility criteria were modeled after those used in the International Duration Evaluation of Adjuvant (IDEA) trial. A target trial emulation and naive observational analysis were conducted. Results from both cohorts were benchmarked against findings from the IDEA trial. Data analysis was conducted from March to December 2020.

Exposure: A shortened duration of adjuvant 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX) chemotherapy, defined as 3 to 5 months of treatment vs 6 months.

Main outcomes and measures: Overall survival assessed via vital statistics. The per-protocol hazard ratio (HR) was estimated using a weighted pooled logistic regression model. Subgroup analyses were conducted by treatment regimen (ie, FOLFOX vs CAPOX) and cancer stage (ie, T1-3 and N1 vs T4 or N2).

Results: From an initial cohort of 3086 patients, 485 (16%) were eligible for inclusion in the target trial analysis. The median age was 59 years (range, 19-81 years), and 230 (47%) were women. The maximum follow-up was 11.6 years. Median overall survival was not reached. A total of 90 patients (19%) died. The 5-year Kaplan Meier overall survival estimate was 0.79 (95% CI, 0.75-0.84). Estimates from the trial emulation were similar to those from the IDEA trial. For example, a shortened duration of adjuvant chemotherapy was not associated with overall survival among patients prescribed CAPOX in the IDEA trial (HR, 0.96; 95% CI, 0.85-1.08) or in the trial emulation (HR, 0.96; 95% CI, 0.43-2.14). In contrast, the naive observational analysis suggested that a shortened duration of CAPOX was significantly associated with worse survival (HR, 3.33; 95% CI, 1.04-10.65).

Conclusions and relevance: In this study, the explicit emulation of a target trial better approximated results from an analogous well-conducted randomized clinical trial.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hilsden reported receiving personal fees from Exact Sciences outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram Describing the Inclusion and Exclusion of Participants Within the Target Trial and Real-World Populations
CAPOX indicates capecitabine plus oxaliplatin; FOLFOX, 5-fluorouracil/leucovorin plus oxaliplatin.
Figure 2.
Figure 2.. Overall Survival Estimates From Target Trial Emulation and Naive Observational Analysis With Those of the International Duration Evaluation of Adjuvant (IDEA) Trial
HR indicates hazard ratio.
See this image and copyright information in PMC

Comment in

  • Trial Emulation and Real-World Evidence.
    Groenwold RHH. Groenwold RHH. JAMA Netw Open. 2021 Mar 1;4(3):e213845. doi: 10.1001/jamanetworkopen.2021.3845. JAMA Netw Open. 2021. PMID: 33783521 No abstract available.

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