Is aflibercept an optimal treatment for wt RAS mCRC patients after progression to first line containing anti-EGFR?

Int J Colorectal Dis. 2020 Apr;35(4):739-746. doi: 10.1007/s00384-020-03509-x. Epub 2020 Feb 15.

Abstract

Purpose: To determine the efficacy and safety data of aflibercept + FOLFIRI in wt RAS mCRC patients after progression to standard chemotherapy + anti-EGFR treatment.

Methods: Retrospective, observational study in real life conducted in wt RAS mCRC patients treated with FOLFIRI-aflibercept after progression to standard first line chemotherapy + anti-EGFR treatment.

Results: A total of 120 patients from 12 Spanish hospitals were enrolled. Median age is 60 years (62.5%/37.5%male/female). Primary tumor site is 24.1%/75.9% right/left-side colon, and 40.8% of patients had a prior resection. All patients had wild-type RAS tumors including 5% of patients with BRAF mutations and received anti-EGFR treatment. At the time aflibercept was initiated, ECOG PS is 0/1 in 96% of patients. Median number of FOLFIRI-aflibercept cycles is 12. Efficacy results: Overall response rate is 33%; progression-free survival (PFS) is 6.9 months (95%CI: 6.1-7.8). Primary tumor resection was the only significant variable related to PFS in the multivariate analysis. Median overall survival (OS) is 14.5 months (95%CI: 9.7-19.3). ECOG and number of metastatic sites were related to OS in multivariate analysis. About 54.1% of patients received a third-line therapy including TAS-102 (23%), regorafenib (18.5%), and capecitabine (9.2%).

Toxicity: Grade 3-4 toxicities were observed in 37.5% of the patients (hematologic 16.6%, hypertension 7.5%, asthenia 5.9%, and perforation 2.5%). Aflibercept dose was reduced in 18.3% of patients.

Conclusions: The results show that patients with wt RAS mCRC who received an anti-EGFR as part of the first-line treatment achieved similar RR, PFS, OS, and toxicities to those reported in VELOUR trial. These results suggest that FOLFIRI-aflibercept after first-line treatment with anti-EGFR is an appropriated option for RAS wt mCRC.

Keywords: Aflibercept; Antiangiogenics; Colorectal cancer; Metastatic colorectal cancer.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Female
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / pharmacology
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use*
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use*
  • Survival Analysis
  • ras Proteins / metabolism*

Substances

  • Recombinant Fusion Proteins
  • aflibercept
  • ErbB Receptors
  • Receptors, Vascular Endothelial Growth Factor
  • ras Proteins
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • IFL protocol