Folfiri-Aflibercept vs. Folfiri-Bevacizumab as Second Line Treatment of RAS Mutated Metastatic Colorectal Cancer in Real Practice

Alessandro Ottaiano, Monica Capozzi, Salvatore Tafuto, Alfonso De Stefano, Chiara De Divitiis, Carmela Romano, Antonio Avallone, Guglielmo Nasti, Alessandro Ottaiano, Monica Capozzi, Salvatore Tafuto, Alfonso De Stefano, Chiara De Divitiis, Carmela Romano, Antonio Avallone, Guglielmo Nasti

Abstract

Background: There are no clinical studies comparing the efficacy of bevacizumab vs.aflibercept in association with folfiri in RAS mutated (RAS-M) metastatic colorectal cancer patients (mCRC) pretreated with folfox and bevacizumab. Patients and Methods: Consecutive RAS-M unresectable mCRC patients progressing to first-line folfox/bevacizumab were treated with 12 cycles of folfiri/bevacizumab (arm A) or folfiri/aflibercept (arm B) at Oncologist discretion. Differences in overall survival between the two schedules were analyzed. Responses and toxicities were described with RECIST and NCI-CTC v4.0, respectively. Results: Seventy-four patients were treated from January 2014 to January 2018; 31 with arm A, 43 with arm B. Among clinical factors there was a predominance of more extended disease (>2 metastatic sites) in arm B (26/43 [60.5%] vs. 10/31 [32.2%] arm A; p = 0.0414). Fifty-nine patients were evaluable for response: arm A, 5 PR (Partial Response), 15 SD (Stable Disease), 8 PD (Progressive Disease); arm B, 5 PR, 16 SD, 10 PD. There were no grade 4 toxic events. Duration of first-line chemotherapy was significantly shorter in patients treated in arm B (12 pts <6 months, 16 pts ≥6, and <12, 15 pts ≥12) vs. arm A (1 pts <6 months, 14 pts ≥6, and <12, 16 pts ≥12) (p = 0.0210); these patients were excluded from survival analysis to avoid prognostic interferences. No maintenance treatment with aflibercept was done in arm B while in arm A bevacizumab with or without fluorouracil and folinic acid were allowed. Median OS were 8.9 months in arm A vs. 12.1 months in arm B (+3.2 months; p = 0.9331, HR: 1.02; 95% CI: 0.57-1.84). Six-months survivals were 65% in arm A and 80% in arm B. Conclusions: Folfiri/bevacizumab and folfiri/aflibercept are equally effective second-line therapies in RAS-M mCRC patients. Although not significant, folfiri/aflibercept was associated with a lower risk of death particularly during the 6-months induction phase.

Keywords: aflibercept; bevacizumab; chemotherapy; colorectal cancer; real practice.

Figures

Figure 1
Figure 1
(A) Study design. (B) Schematic representation of study time points.
Figure 2
Figure 2
Kaplan-Meyer survival curves according to second-line chemotherapy (Arm A: folfiri/bevacizumab; Arm B: folfiri/aflibercept).

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