Phase II randomized trial of carboplatin, paclitaxel, bevacizumab with or without cixutumumab (IMC-A12) in patients with advanced non-squamous, non-small-cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E3508)

Athanassios Argiris, J. W. Lee, J. Stevenson, M. G. Sulecki, V. Hugec, N. W. Choong, J. N. Saltzman, W. Song, R. M. Hansen, T. L. Evans, S. S. Ramalingam, J. H. Schiller

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: Cixutumumab is a fully human IgG1 monoclonal antibody to the insulin-like growth factor type I receptor that can potentially reverse resistance and enhance the efficacy of chemotherapy. Methods: Bevacizumab-eligible patients with stage IV or recurrent non-squamous, non-small-cell lung cancer and good performance status were randomized to receive standard doses of paclitaxel, carboplatin, and bevacizumab to a maximum of six cycles followed by bevacizumab maintenance (CPB) until progression (arm A) or CPB plus cixutumumab 6 mg/kg i.v. weekly (arm B). Results: Of 175 patients randomized, 153 were eligible and treated (78 in arm A; 75 in arm B). The median progression-free survival was 5.8 months (95% CI 5.4-7.1) in arm A versus 7 months (95% CI 5.7-7.6) in arm B (P=0.33); hazard ratio 0.92 (95% CI 0.65-1.31). Objective response was 46.2% versus 58.7% in arm A versus arm B (P=0.15). The median overall survival was 16.2 months in arm A versus 16.1 months in arm B (P=0.95). Grade 3/4 neutropenia and febrile neutropenia, thrombocytopenia, fatigue, and hyperglycemia were increased with cixutumumab. Conclusions: The addition of cixutumumab to CPB increased toxicity without improving efficacy and is not recommended for further development in non-small-cell lung cancer. Both treatment groups had longer OS than historical controls which may be attributed to several factors, and emphasizes the value of a comparator arm in phase II trials.

Original languageEnglish (US)
Pages (from-to)3037-3043
Number of pages7
JournalAnnals of Oncology
Volume28
Issue number12
DOIs
StatePublished - Dec 1 2017

Keywords

  • Bevacizumab
  • Carboplatin
  • Cixutumumab
  • Non-small-cell lung cancer
  • Paclitaxel

ASJC Scopus subject areas

  • Hematology
  • Oncology

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