Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2016 Sep;11(9):1511-21.
doi: 10.1016/j.jtho.2016.05.028. Epub 2016 Jun 11.

Outcome and Biomarker Analysis from a Multicenter Phase 2 Study of Ipilimumab in Combination with Carboplatin and Etoposide as First-Line Therapy for Extensive-Stage SCLC

Edurne Arriola  1 , Matthew Wheater  2 , Ian Galea  3 , Nadia Cross  4 , Tom Maishman  4 , Debbie Hamid  4 , Louise Stanton  4 , Judith Cave  2 , Tom Geldart  5 , Clive Mulatero  6 , Vannessa Potter  7 , Sarah Danson  8 , Pennella J Woll  8 , Richard Griffiths  9 , Luke Nolan  2 , Christian Ottensmeier  10
Affiliations
Clinical Trial

Outcome and Biomarker Analysis from a Multicenter Phase 2 Study of Ipilimumab in Combination with Carboplatin and Etoposide as First-Line Therapy for Extensive-Stage SCLC

Edurne Arriola et al. J Thorac Oncol. 2016 Sep.

Abstract

Objectives: Our aim was to evaluate the safety and efficacy of ipilimumab combined with standard first-line chemotherapy for patients with extensive-stage SCLC.

Methods: Patients with chemotherapy-naive extensive-stage SCLC were treated with carboplatin and etoposide for up to six cycles. Ipilimumab, 10 mg/kg, was given on day 1 of cycles 3 to 6 and every 12 weeks. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0, and immune-related response criteria. The primary end point was 1-year progression-free survival (PFS) according to RECIST. Secondary end points included PFS according to immune-related PFS and overall survival. Autoantibody serum levels were evaluated and correlated with clinical outcomes.

Results: A total of 42 patients were enrolled between September 2011 and April 2014; 39 were evaluable for safety and 38 for efficacy. Six of 38 patients (15.8% [95% confidence interval (CI): 7.4-30.4]) were alive and progression-free at 1-year by RECIST. Median PFS was 6.9 months (95% CI: 5.5-7.9). Median immune-related PFS was 7.3 months (95% CI: 5.5-8.8). Median overall survival was 17.0 months (95% CI: 7.9-24.3). Of the patients evaluable for response, 21 of 29 (72.4%) achieved an objective response by RECIST and 28 of 33 (84.8%) achieved an objective response by the immune-related response criteria. All patients experienced at least one adverse event; at least one grade 3 or higher toxicity developed in 35 of 39 patients (89.7%); in 27 patients (69.2%) this was related to ipilimumab. Five deaths were reported to be related to ipilimumab. Positivity of an autoimmune profile at baseline was associated with improved outcomes and severe neurological toxicity.

Conclusions: Ipilimumab in combination with carboplatin and etoposide might benefit a subgroup of patients with advanced SCLC. Autoantibody analysis correlates with treatment benefit and toxicity and warrants further investigation.

Keywords: Autoantibodies; Biomarker; CTLA-4 immunotherapy; Ipilimumab; Small cell lung cancer.

PubMed Disclaimer

Figures

Supplementary Figure 1
Supplementary Figure 1
Supplementary Figure 2
Supplementary Figure 2
Figure 1
Figure 1
CONSORT diagram showing the disposition of patients in the ICE (ipilimumab, carboplatin, and etoposide) study. ITT, intention to treat.
Figure 2
Figure 2
Kaplan-Meier plots for progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0, (A) and immune-related response criteria (B) and according to autoantibody status at baseline (C). CI, confidence interval; irRC, immune-related response criteria; NR, not reached.
Figure 3
Figure 3
Kaplan-Meier plots for overall survival (A) and according to autoantibody status at baseline (B). OS, overall survival; CI, confidence interval.
See this image and copyright information in PMC

References

    1. Oze I., Hotta K., Kiura K. Twenty-seven years of phase III trials for patients with extensive disease small-cell lung cancer: disappointing results. PloS One. 2009;4:e7835. - PMC - PubMed
    1. Slotman B.J., van Tinteren H., Praag J.O. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015;385:36–42. - PubMed
    1. Ettinger D.S., Finkelstein D.M., Abeloff M.D. A randomized comparison of standard chemotherapy versus alternating chemotherapy and maintenance versus no maintenance therapy for extensive-stage small-cell lung cancer: a phase III study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1990;8:230–240. - PubMed
    1. Arnold A.M., Seymour L., Smylie M. Phase II study of vandetanib or placebo in small-cell lung cancer patients after complete or partial response to induction chemotherapy with or without radiation therapy: National Cancer Institute of Canada Clinical Trials Group Study BR.20. J Clin Oncol. 2007;25:4278–4284. - PubMed
    1. Pujol J.L., Breton J.L., Gervais R. Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: an intergroup study FNCLCC cleo04 IFCT 00-01. J Clin Oncol. 2007;25:3945–3951. - PubMed

Publication types

MeSH terms