Randomized phase II study of erlotinib in combination with placebo or R1507, a monoclonal antibody to insulin-like growth factor-1 receptor, for advanced-stage non-small-cell lung cancer - PubMed (original) (raw)

Clinical Trial

. 2011 Dec 1;29(34):4574-80.

doi: 10.1200/JCO.2011.36.6799. Epub 2011 Oct 24.

David R Spigel, David Chen, Martin B Steins, Jeffrey A Engelman, Claus-Peter Schneider, Silvia Novello, Wilfried E E Eberhardt, Lucio Crino, Kai Habben, Lian Liu, Pasi A Jänne, Carrie M Brownstein, Martin Reck

Affiliations

Clinical Trial

Randomized phase II study of erlotinib in combination with placebo or R1507, a monoclonal antibody to insulin-like growth factor-1 receptor, for advanced-stage non-small-cell lung cancer

Suresh S Ramalingam et al. J Clin Oncol. 2011.

Abstract

Purpose: R1507 is a selective, fully human, recombinant monoclonal antibody (immunoglobulin G1 subclass) against insulin-like growth factor-1 receptor (IGF-1R). The strong preclinical evidence supporting coinhibition of IGF-1R and epidermal growth factor receptor (EGFR) as anticancer therapy prompted this study.

Patients and methods: Patients with advanced-stage non-small-cell lung cancer (NSCLC) with progression following one or two prior regimens, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, and measurable disease were eligible. Patients were randomly assigned to receive erlotinib (150 mg orally once a day) in combination with either placebo, R1507 9 mg/kg weekly, or R1507 16 mg/kg intravenously once every 3 weeks. Treatment cycles were repeated every 3 weeks. The primary end point was comparison of the 12-week progression-free survival (PFS) rate.

Results: In all, 172 patients were enrolled: median age, 61 years; female, 33%; never-smokers, 12%; and performance status 0 or 1, 88%. The median number of R1507 doses was six for the weekly arm and 3.5 for the every-3-weeks arm. Grades 3 to 4 adverse events occurred in 37%, 44%, and 48% of patients with placebo, R1507 weekly, and R1507 every 3 weeks, respectively. The 12-week PFS rates were 39%, 37%, and 44%, and the median overall survival was 8.1, 8.1, and 12.1 months for the three groups, respectively, with statistically nonsignificant hazard ratios. The 12-week PFS rate in patients with KRAS mutation was 36% with R1507 compared with 0% with placebo.

Conclusion: The combination of R1507 with erlotinib did not provide PFS or survival advantage over erlotinib alone in an unselected group of patients with advanced NSCLC. Predictive biomarkers are essential for further development of combined inhibition of IGF-1R and EGFR.

Trial registration: ClinicalTrials.gov NCT00760929.

PubMed Disclaimer

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Fig 1.

CONSORT diagram for treatment assignment. R1507, selective, fully human, recombinant monoclonal antibody against insulin-like growth factor-1 receptor.

Fig 2.

Fig 2.

Kaplan-Meier curve for (A) progression-free survival and (B) overall survival.

Similar articles

Cited by

References

    1. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–132. - PubMed
    1. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–2139. - PubMed
    1. Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2005;2:e17. - PMC - PubMed
    1. Guix M, Faber AC, Wang SE, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest. 2008;118:2609–2619. - PMC - PubMed
    1. Desbois-Mouthon C, Cacheux W, Blivet-Van Eggelpoël MJ, et al. Impact of IGF-1R/EGFR cross-talks on hepatoma cell sensitivity to gefitinib. Int J Cancer. 2006;119:2557–2566. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources