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

doi:10.1016/j.jtho.2016.05.028

Journal of Thoracic Oncology

Volume 11, Issue 9, September 2016, Pages 1511-1521

https://doi.org/10.1016/j.jtho.2016.05.028 Get rights and content

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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

Small cell lung cancer

Ipilimumab

Autoantibodies

Biomarker

CTLA-4 immunotherapy

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: Disclosure: Dr. Arriola declares nonfinancial support from AstraZeneca and personal fees from Lilly outside the submitted work. Dr. Mulatero reports personal fees from Clovis Oncology, PRMA consulting, Novartis, Lilly, Pfizer, GlaxoSmithKline, Ernst and Young, Amgen, and Astra Zeneca; personal fees, nonfinancial support, and research funding from Boehringer Ingelheim; and research funding and nonfinancial support from Bristol-Myers Squibb, Pierre Fabre, Merck Sharp and Dome, and Roche outside the submitted work. Dr. Danson reports research funding from Astex Pharmaceuticals, Lilly, Plexicon, Bayer, Synta, Amgen, Boehringer Ingelheim, and GlaxoSmithKline; nonfinancial support and other from Bristol-Myers Squibb; and nonfinancial support from Merck Sharp and Dohme outside the submitted work. Dr. Geldart declares personal fees from Bristol-Myers Squibb and Pfizer outside the submitted work. Dr. Wheater declares personal fees and nonfinancial support from Bristol-Myers Squibb outside the submitted work. Dr. Griffiths declares personal fees from Bristol-Myers Squibb outside the submitted work. Dr. Cave reports nonfinancial support from Novartis, Boehringer Ingelheim, and Lilly outside the submitted work. Dr. Woll reports nonfinancial support from Bristol-Myers Squibb outside the submitted work. Dr. Nolan declares personal fees from Bristol-Myers Squibb and Merck outside the submitted work. Dr. Ottensmeier reports grants from Bristol Myers Squibb during the conduct of the study; he also reports personal fees from Transgene, Bristol Myers Squibb, Immatics, and Merck; research funding from Inovio; personal fees, nonfinancial support, and other from Bristol-Myers Squibb and Merck Sharp and Dohme; other from Verastem, Biontech AG, Serametrix, and Touchlight Genetics; and personal fees and nonfinancial support from Roche outside the submitted work. The remaining authors declare no conflict of interest.