Arriola, Edurne, Wheater, Matthew, Galea, Ian, Cross, Nadia, Maishman, Tom, Hamid, Debbie, Stanton, Louise, Cave, Judith, Geldart, Tom, Mulatero, Clive et al (show 6 more authors)
(2016)
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.
JOURNAL OF THORACIC ONCOLOGY, 11 (9).
pp. 1511-1521.
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Outcome and Biomarker Analysis from a Multicenter Phase 2 Study of Ipilimumab in Combination with Carboplatin and Etoposide .pdf - Published version Download (938kB) | Preview |
Abstract
<h4>Objectives</h4>Our aim was to evaluate the safety and efficacy of ipilimumab combined with standard first-line chemotherapy for patients with extensive-stage SCLC.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Small cell lung cancer, Ipilimumab, Autoantibodies, Biomarker, CTLA-4 immunotherapy |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Apr 2023 15:53 |
| Last Modified: | 18 Apr 2023 15:53 |
| DOI: | 10.1016/j.jtho.2016.05.028 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3169669 |
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