Aflibercept Plus FOLFIRI for Second-line Treatment of Metastatic Colorectal Cancer: Observations from the Global Aflibercept Safety and Health-Related Quality-of-Life Program (ASQoP)

Clin Colorectal Cancer. 2019 Sep;18(3):183-191.e3. doi: 10.1016/j.clcc.2019.05.003. Epub 2019 May 15.

Abstract

Background: The objectives of this study were to evaluate the safety profile of aflibercept and health-related quality of life (HRQL) in patients with metastatic colorectal cancer (mCRC) provided with aflibercept access before marketing authorization.

Patients and methods: Patients received aflibercept followed by FOLFIRI (fluorouracil, leucovorin, irinotecan) on day 1 of a 2-week cycle until disease progression, unacceptable toxicity, death, or patient/investigator decision to discontinue. Treatment-emergent adverse events (TEAEs) were evaluated, and HRQL was assessed at baseline, cycle 3, and every other cycle using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29, and EuroQol 5-Dimensions 3-Levels questionnaires (NCT01571284).

Results: Overall, 779 adult patients with mCRC, who received ≥ 1 prior oxaliplatin-based regimen and had disease progression during or following their last administration of oxaliplatin-based chemotherapy, were enrolled. At data cutoff, all patients had discontinued treatment, mainly owing to disease progression (51.7%). The most common TEAEs of any grade were diarrhea (61.6%), hypertension (48.4%), and nausea (43.3%). The most common grade 3/4 TEAEs were hypertension (24.1%), neutropenia (23.1%), and diarrhea (15.3%). Clinically meaningful changes in HRQL were reported for all measures. Most patients either had an improvement in their HRQL scores or remained stable during the treatment period based on patient-reported outcomes.

Conclusion: The data from this study support the tolerability of the combination of aflibercept and FOLFIRI in a setting that more closely approximates real life in patients with mCRC who failed to respond to oxaliplatin-based chemotherapy, and also suggest an improvement in HRQL.

Keywords: Antiangiogenic; Colorectal neoplasms; Patient-reported outcome measures; Receptors; Vascular endothelial growth factor.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Diarrhea / chemically induced
  • Diarrhea / diagnosis
  • Diarrhea / epidemiology
  • Disease Progression
  • Female
  • Fluorouracil / adverse effects
  • Follow-Up Studies
  • Humans
  • Hypertension / chemically induced
  • Hypertension / diagnosis
  • Hypertension / epidemiology
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / diagnosis
  • Nausea / epidemiology
  • Neutropenia / chemically induced
  • Neutropenia / diagnosis
  • Neutropenia / epidemiology
  • Patient Reported Outcome Measures
  • Quality of Life*
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins / adverse effects*
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

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

Supplementary concepts

  • IFL protocol

Associated data

  • ClinicalTrials.gov/NCT01571284