Aflibercept Plus FOLFIRI in the Real-life Setting: Safety and Quality of Life Data From the Italian Patient Cohort of the Aflibercept Safety and Quality-of-Life Program Study

Clin Colorectal Cancer. 2018 Sep;17(3):e457-e470. doi: 10.1016/j.clcc.2018.03.002. Epub 2018 Mar 8.

Abstract

Background: Aflibercept combined with FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) as second-line treatment of metastatic colorectal cancer (mCRC) significantly improved survival compared with FOLFIRI alone in the pivotal VELOUR (aflibercept vs. placebo in combination with irinotecan and 5-fluorouracil in the treatment of patients with metastatic colorectal cancer after failure of an oxaliplatin-based regimen) trial. No quality-of-life assessment was performed in VELOUR; therefore, the ASQoP (Aflibercept Safety and Quality-of-Life Program) trial was designed to capture the safety and health-related quality of life (HRQL).

Patients and methods: ASQoP was an international, open-label, single-arm trial evaluating the safety and HRQL of aflibercept combined with FOLFIRI administered in a real-life setting to 781 patients with mCRC, pretreated with an oxaliplatin-based regimen with or without bevacizumab. The Italian subset of ASQoP enrolled 200 patients from 28 institutions. The primary endpoint was safety; HRQL was a secondary endpoint, assessed by validated questionnaires (European quality of life 5-dimension instrument 3-level; European Organization for Research and Treatment for Cancer Quality of Life Questionnaire Core 30, version 3; and EORTC-CR29) at baseline, during treatment, and at the end of treatment.

Results: The median age of the Italian ASQoP population was 63 years; the median number of aflibercept and FOLFIRI cycles was 7. Treatment-emergent adverse events were reported in 97.5% of patients. Hypertension (28.5%), neutropenia (27.5%; from laboratory data), asthenic conditions (20.0%), diarrhea (17.0%), and stomatitis (13.0%) were the most frequent (incidence, ≥ 5%) grade 3/4 toxicities. One toxic death occurred during the study period due to sepsis, without neutropenic complications. No significant worsening of HRQL was shown during treatment.

Conclusion: Aflibercept combined with FOLFIRI was well tolerated when administered as second-line treatment for patients with mCRC in a real-life setting. It did not affect HRQL and showed similar rates of treatment-emergent adverse events as those observed in the VELOUR trial. No new safety signals were identified.

Keywords: Antiangiogenesis; Antivascular endothelial growth factor agents; HRQL; Metastatic colorectal cancer; Targeted therapy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Asthenia / chemically induced
  • Asthenia / epidemiology
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Cohort Studies
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Diarrhea / chemically induced
  • Diarrhea / epidemiology
  • Disease Progression
  • Female
  • Fluorouracil / adverse effects
  • Humans
  • Hypertension / chemically induced
  • Hypertension / epidemiology
  • Italy / epidemiology
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / epidemiology
  • Progression-Free Survival
  • Quality of Life*
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins / adverse effects*
  • Stomatitis / chemically induced
  • Stomatitis / epidemiology
  • Surveys and Questionnaires / statistics & numerical data

Substances

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

Supplementary concepts

  • IFL protocol