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. 2018 Sep;17(3):e593-e599.
doi: 10.1016/j.clcc.2018.05.009. Epub 2018 Jun 1.

Previous Bevacizumab and Efficacy of Later Anti-Epidermal Growth Factor Receptor Antibodies in Metastatic Colorectal Cancer: Results From a Large International Registry

Matthew Burge  1 , Christine Semira  2 , Belinda Lee  3 , Margaret Lee  4 , Suzanne Kosmider  5 , Rachel Wong  6 , Jeremy Shapiro  7 , Brigette Ma  8 , Andrew P Dean  9 , Allan S Zimet  10 , Simone A Steel  11 , Sheau Wen Lok  12 , Javier Torres  13 , Melissa Eastgate  14 , Hui-Li Wong  3 , Peter Gibbs  15
Affiliations

Previous Bevacizumab and Efficacy of Later Anti-Epidermal Growth Factor Receptor Antibodies in Metastatic Colorectal Cancer: Results From a Large International Registry

Matthew Burge et al. Clin Colorectal Cancer. 2018 Sep.

Abstract

Background: The FIRE-3 [5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus cetuximab versus FOLFIRI plus bevacizumab in first line treatment colorectal cancer (CRC)] study reported that first-line FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab resulted in similar progression-free survival (PFS) but improved overall survival (OS). A potential explanation is that the initial biologic agent administered in metastatic CRC (mCRC) affects later line efficacy of the other treatments. We sought to test this hypothesis.

Materials and methods: We interrogated our mCRC registry (Treatment of Recurrent and Advanced Colorectal Cancer) regarding treatment and outcome data for RAS wild-type patients receiving epidermal growth factor receptor inhibitors (EGFRIs) in second and subsequent lines. Survival outcomes from the beginning of EGFRI use were determined as a function of previous bevacizumab use and the interval between ceasing bevacizumab and beginning EGFRI use.

Results: Of 2061 patients, 222 eligible patients were identified, of whom 170 (77%) had received previous bevacizumab and 52 (23%) had not. PFS and OS from the start of EGFRIs did not differ by previous bevacizumab use (3.8 vs. 4.2 months; hazard ratio [HR], 1.12; P = .81; 9.0 vs. 9.2 months; HR, 1.19; P = .48, respectively) for the whole cohort or when analyzed by the primary tumor side (HR for left side, 1.07; P = .57; HR for right side, 1.2; P = .52). PFS was significantly shorter with right-sided primary tumors when the interval between bevacizumab and EGFRI use was < 6 versus > 6 months (median, 2.2 vs. 6 months; HR, 2.23; P = .01) but not with left-sided tumors (median, 4.2 vs. 5.5 months; HR, 1.12; P = .26).

Conclusion: Previous bevacizumab use had no effect on the activity of subsequent EGFRIs. The apparent effect of time between biologic agents in right-sided tumors might reflect patient selection.

Keywords: Biologic agents; Interaction; Sequencing; Survival; Timing.

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