Real-world uptake and effectiveness of triplet versus doublet chemotherapy with bevacizumab in patients with metastatic colorectal cancer in the United States

Abstract

Introduction

Triplet chemotherapy + bevacizumab (TripletBev) demonstrated an overall survival (OS) benefit for patients with newly diagnosed metastatic colorectal cancer in randomized trials. We aimed to evaluate the uptake and estimate the effectiveness of TripletBev versus doublet chemotherapy + bevacizumab (DoubletBev) in a real-world population in the United States.

Methods

We carried out a retrospective cohort study of patients initiating first-line treatment of metastatic colorectal cancer between 23 October 2014 and 31 October 2022 using the Flatiron Health nationwide electronic health record (EHR)-derived de-identified database. The data originated from ∼280 cancer clinics (∼800 sites of care) in the USA. The primary analysis compared OS between patients receiving TripletBev or DoubletBev using a Cox proportional hazards model with adjustment for pre-specified covariates using stabilized inverse probability of treatment weighting. This analysis was also carried out within pre-specified and post hoc subgroups. A secondary analysis used Stürmer-trimming of the propensity score distribution to include patients most likely to be eligible to receive either treatment.

Results

Some 391 patients received TripletBev and 9625 received DoubletBev. There was no association between TripletBev and OS in the primary analysis [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.75-1.13]. TripletBev was associated with lower hazard of death in patients with synchronous metastases (HR 0.79; 95% CI 0.64-0.98; statistically significant) and in the secondary analysis of patients most likely to be eligible to receive either treatment (HR 0.80; 95% CI 0.63-1.02; non-statistically significant).

Conclusion

Uptake of TripletBev remains low and the primary analysis did not demonstrate effectiveness in a real-world population in the United States. Patients with synchronous metastases and those most likely to be eligible to receive either treatment may be most likely to benefit from TripletBev.