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Ann Oncol. 2017 Dec 1;28(12):3037-3043. doi: 10.1093/annonc/mdx534.

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).

Author information

1
Medical Oncology, Hygeia Hospital, Athens, Greece.
2
Medical Oncology, Thomas Jefferson University, Philadelphia.
3
Dana-Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston.
4
Medical Oncology, Cleveland Clinic Foundation, Cleveland.
5
Medical Oncology, University of Pittsburgh Cancer Institute, Pittsburgh.
6
Medical Oncology, Minnesota Oncology, Minneapolis, Lake Elmo.
7
Genentech, Inc., South San Francisco.
8
Medical Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland.
9
Pottstown Memor Reg Cancer Ctr, Pottstown.
10
Medical Oncology, Oconomowoc Memorial Hospital, Oconomowoc.
11
Medical Oncology, University of Pennsylvania, Philadelphia.
12
The Winship Cancer Institute of Emory University, Atlanta.
13
Medical Oncology, The University of Texas Southwestern Medical Center, Dallas, USA.

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.

ClinicalTrials.gov Identifier:

NCT00955305.

KEYWORDS:

bevacizumab; carboplatin; cixutumumab; non-small-cell lung cancer; paclitaxel

PMID:
28950351
PMCID:
PMC5834066
[Available on 2018-12-01]
DOI:
10.1093/annonc/mdx534
[Indexed for MEDLINE]

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