Abstract

Triplet chemotherapy with fluorouracil, folinic acid, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-B) is an effective first-line treatment option for patients with metastatic colorectal cancer (mCRC). However, the degree of implementation of FOLFOXIRI-B in daily practice is unknown. To evaluate the current adoption rate of FOLFOXIRI-B in patients with mCRC and investigate the perspectives of medical oncologists toward this treatment option. This 1-week, multicenter, cross-sectional study in the Netherlands used a flash mob design, which facilitates ultrafast data generation (flash) through the engagement of numerous researchers (mob). During the study week (March 1-5, 2021), patient data were retrieved from electronic health records of 47 hospitals on patients with mCRC who were referred to a medical oncologist between November 1, 2020, and January 31, 2021. Interviews were simultaneously conducted with 101 medical oncologists from 52 hospitals who regularly treat patients with mCRC. First-line systemic treatment as determined by the treating physician. The FOLFOXIRI-B prescription rate was the main outcome. Current practice was compared with prescription rates in 2015 to 2018. Eligibility for treatment with FOLFOXIRI-B was estimated. An exploratory outcome was medical oncologists' reported perspectives on FOLFOXIRI-B. A total of 5948 patients in the Netherlands (median age [interquartile range], 66 [57-73] years; 3503 [59%] male; and 3712 [62%] with left-sided or rectal tumor) were treated with first-line systemic therapy for synchronous mCRC. A total of 282 patients with mCRC underwent systemic therapy during the study period (2021). Of these 282 patients, 199 (71%) were treated with intensive first-line therapy other than FOLFOXIRI-B, of whom 184 (65%) were treated with oxaliplatin doublets with or without bevacizumab; 14 (5%) with irinotecan doublets with or without bevacizumab, panitumumab, or cetuximab; and 1 (0.4%) with irinotecan with bevacizumab. Fifty-four patients (19%) were treated with fluoropyrimidine monotherapy with or without bevacizumab, 1 patient (0.4%) with panitumumab monotherapy, and 3 (1%) with immune checkpoint inhibitors. In total, 25 patients (9%; 95% CI, 6%-12%) were treated with first-line FOLFOXIRI-B compared with 142 (2%; 95% CI, 2%-3%) in 2015 to 2018. During the study period, 21 of 157 eligible patients (13.4%) in the Netherlands were treated with FOLFOXIRI-B. A total of 87 medical oncologists (86%) reported discussing FOLFOXIRI-B as a treatment option with eligible patients. A total of 47 of 85 (55%) generally communicated a preference for a chemotherapy doublet to patients. These oncologists reported a significantly lower awareness of guidelines and trial results. Toxic effects were the most reported reason to prefer an alternative regimen. The findings of this study suggest that FOLFOXIRI-B prescription rates have marginally increased in the last 5 years. Considering that most medical oncologists discuss this treatment option, the prescription rate found in this study was below expectations. Awareness of guidelines and trial data seems to contribute to the discussion of available treatment options by medical oncologists, and the findings of this study suggest a need for repeated and continuing medical education.

Highlights

  • In the past 2 decades, the choice of first-line treatment of patients with metastatic colorectal cancer has become more complex because of the increased availability of treatment options.[1]

  • The findings of this study suggest that FOLFOXIRI-B prescription rates have marginally increased in the last 5 years

  • Considering that most medical oncologists discuss this treatment option, the prescription rate found in this study was below expectations

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Summary

Introduction

In the past 2 decades, the choice of first-line treatment of patients with metastatic colorectal cancer (mCRC) has become more complex because of the increased availability of treatment options.[1]. Additional evidence for FOLFOXIRI-B was recently provided by the TRIBE2 (Upfront FOLFOXIRI Plus Bevacizumab and Reintroduction After Progression Versus mFOLFOX6 Plus Bevacizumab Followed by FOLFIRI Plus Bevacizumab in the Treatment of Patients With Metastatic Colorectal Cancer) trial in 2020,4 which demonstrated that upfront FOLFOXIRI-B, followed by reintroduction after first disease progression, was superior to sequential administration of fluorouracil, oxaliplatin, and folinic acid plus bevacizumab (FOLFOX-B) and FOLFIRI-B (statistically significant benefit in progression-free survival 2 of 2.8 months and, as a secondary end point, in overall survival of 4.9 months) The efficacy of this regimen was confirmed in a meta-analysis[9] that included all available data from randomized clinical trials. Because FOLFOXIRI-B has not been prospectively compared to doublet chemotherapy plus an antibody to the epidermal growth factor receptor in patients with left-sided primary and RAS (OMIM 164790, 190070, and 19002090070)/BRAFV600 (OMIM 164757) wild-type tumors, its benefit in this subgroup is uncertain

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