To date the treatment of RAS mutated (-M) metastatic colorectal cancer (mCRC) patients (pts) relies on the administration of oxaliplatin-based chemotherapy and bevacizumab as first line. Intensive debate is open about second-line treatments.
This is a real practice study; consecutive RAS-M unresectable mCRC were treated at the oncologist discretion at progression to FOLFOX/BEVA (fluorouracil, folinic acid, oxaliplatin, bevacizumab) with FOLFIRI/BEVA (fluorouracil, folinic acid, irinotecan, bevacizumab) (arm A) or FOLFIRI/AFLI (FOLFIRI, aflibercept) (arm B). We have analyzed differences in outcome and response between the two therapy sequences.
Seventy-four patients were treated from January 2014 to January 2018; 31 treated with arm A, 43 with arm B. Among clinical factors there was a predominance of more extended disease (>two metastatic sites) in arm B (25/31 [51.2%] vs 40/43 [32.3 %] arm A; p = 0.0414). Fifty-nine pts were evaluable for response through RECIST: arm A, 5 PR, 15 SD, 8 PD; arm B, 5 PR, 16 SD, 10 PD. Second-line chemotherapy doses were reduced in 32.3% of pts in arm A and 38.1% in arm B. There were no grade 4 toxic events (NCI-CTC v4.0). The mean distance from first-line discontinuation to second-line start was 0.8 months in arm A and 2.4 months in arm B. Duration of first-line chemotherapy was significantly shorter in pts treated in arm B (12 pts < 6 months arm B vs 1 pt in arm A; p = 0.0278). Analysis of overall survival (OS) was done excluding these 13 pts to avoid prognostic interferences. Median OS were 22.7 in arm A vs 25.5 months in arm B (+ 2.8 months; P = 0.6855, HR: 1.12; 95% CI: 0.62 to 2.03). No maintenance treatment was done in arm B while in arm A BEVA with or without fluorouracil and folinic acid was done; censoring the analysis of OS at the end of the induction phase of both arms favored arm B (P = 0.0425; HR: 0.42; 95% CI: 0.15 to 1.15).
In our real practice, oncologists tend to administer FOLFIRI/AFLI in more extended RAS-M mCRC and to delay start of therapy. FOLFIRI/BEVA and FOLFIRI/AFLI are equally effective second-lines albeit FOLFIRI/AFLI, during the induction phase (6 months), is associated with a lower risk of death.
Clinical trial identification
Legal entity responsible for the study
Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”.
Has not received any funding.
All authors have declared no conflicts of interest.