Double or nothing? Choice of first-line chemotherapy in a real world metastatic colorectal cancer cohort results from the TRACC registry

Abstract

Background: Fluoropyrimidine doublets are the instinctive choice for most Australian oncologists treating first-line metastatic colorectal cancer (mCRC). Accepted alternatives, supported by multiple randomised studies, include single-agent fluoropyrimidine (FP), which is associated with a similar overall survival (OS) when compared with doublets. Whilst combination therapies are associated with greater treatment response, intensifying treatment from single, to doublet and triplet chemotherapy is associated with increased toxicity.

Methods: Data were analysed from TRACC, a large multisite Australian cancer registry collecting prospective demographic, tumour, treatment and outcome data for mCRC. We identified patients <75 years treated with first-line chemotherapy between 2009 and 2020, and determined the proportion treated with single-agent FP, doublet or triplet chemotherapy (with or without a biologic). Log-rank testing and Kaplan Meier curves were used to compare PFS and OS for FP versus doublet cohorts.

Results: Of 2196 patients in TRACC, 1402 (63.8%) met study criteria. The majority received doublets (1237, 88.3%), with fewer receiving single-agent FP (145 = 10.3%) or triplet regimens (20 = 1.4%). Use of triplet (FOLFOXIRI) increased over time, with 9% receiving triplet therapy by 2020. Those receiving FP alone were older than those receiving doublet (median age 66 v 60 years), had a poorer performance status (ECOG 0%–1 74% v 93%) and greater comorbidity (Charlson comorbidity index > 3 in 59% v 30%). Patients receiving initial FP had inferior PFS compared with doublets (mPFS 7.5 v 10.8 months [HR 1.45, p < 0.0001]), but there was no difference in OS (mOS 24.8 v 27.4 months [HR 1.2, p = 0.1]).

Conclusions: Doublet regimens are the dominant paradigm in mCRC in the first-line setting, despite the lack of OS advantage demonstrated in randomised clinical trials. Our local registry data supports this, despite prognostic factors biasing against FP alone. Use of triplet therapy, where an OS advantage has been demonstrated, is increasing.