Phase II trial of weekly alternating sequential BIBF 1120 and afatinib for advanced colorectal cancer

Anticancer Res. 2011 Jun;31(6):2271-81.

Abstract

Aim: The feasibility of an alternating regimen of BIBF 1120, a potent, oral, triple angiokinase inhibitor, and afatinib (BIBW 2992), a potent ErbB family blocker, was explored in patients with advanced pretreated colorectal cancer (CRC).

Patients and methods: Patients received repeated courses of alternating 7-day treatment periods, first with BIBF 1120 250 mg twice daily and then afatinib 50 mg once daily. The primary endpoint was the objective response rate; the incidence/severity of adverse events (AEs) and pharmacokinetics (PK) were determined.

Results: Forty-six patients (≥4 prior lines, most anti-VEGF and/or -EGFR pretreated) received BIBF 1120 and afatinib. No objective responses were observed; the best response was stable disease in 20 patients (43.5%). Seven patients (15.2%) remained progression-free for ≥16 weeks. Median progression-free survival was 1.9 months; median overall survival was 5.5 months. The most frequent drug-related AEs were diarrhoea (80.4%), asthenia (47.8%), nausea (43.5%) and rash (41.3%). PK assessments did not show obvious alterations for either drug.

Conclusion: Weekly alternating administration of BIBF 1120 and afatinib is feasible; however, its efficacy was limited in this highly palliative patient population.

Publication types

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

MeSH terms

  • Afatinib
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Disease-Free Survival
  • Drug Administration Schedule
  • Humans
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Indoles / pharmacokinetics
  • Male
  • Middle Aged
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics
  • Survival Rate

Substances

  • Indoles
  • Quinazolines
  • Afatinib
  • nintedanib