Randomized phase II study of carboplatin and etoposide with or without obatoclax mesylate in extensive-stage small cell lung cancer.

Abstract

OBJECTIVE:

This randomized phase II study assessed the efficacy and safety of obatoclax mesylate, a small-molecule Bcl-2 inhibitor, added to carboplatin/etoposide chemotherapy as initial treatment for extensive-stage small-cell lung cancer (ES-SCLC).

MATERIALS AND METHODS:

Chemotherapy-naïve subjects with ES-SCLC and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 received carboplatin/etoposide with (CbEOb) or without (CbE) obatoclax for up to six cycles. Responders to CbEOb could receive maintenance obatoclax until disease progression. The primary endpoint was objective response rate (ORR).

RESULTS:

155 subjects (median age 62, 58% male, 10% ECOG PS 2) were treated with CbEOb (n=77) or CbE (n=78); 65% and 59% of subjects, respectively, completed six cycles. ORR was 62% with CbEOb versus 53% with CbE (1-sided p=0.143). Clinical benefit (ORR+ stable disease) trended better with CbEOb (81% versus 68%; p=0.054). Median progression-free survival (PFS) and overall survival (OS) were 5.8 months (95% confidence interval [CI]: 5.3-6.5) and 10.5 months (8.9-13.8) with CbEOb and 5.2 months (95% CI: 4.1-5.7) and 9.8 months (7.2-11.2) with CbE. Median OS was 10.5 months (95% CI: 8.9-13.8) and 9.8 months (7.2-11.2) with a nonsignificant hazard ratio for OS, 0.823; 1-sided p=0.121. Grade 3/4 adverse events (AEs) were primarily hematologic and similar in frequency between treatment arms. Obatoclax-related somnolence and euphoria were grade 1/2, transient, and did not require treatment discontinuation.

CONCLUSION:

Obatoclax was well tolerated when added to carboplatin/etoposide in first-line treatment of ES-SCLC, but failed to significantly improve ORR, PFS, or OS.

• Authors: Corey J Langer, Istvan Albert, Helen J Ross, Peter Kovacs, L Johnetta Blakely, Gabor Pajkos, Attila Somfay, Petr Zatloukal, Andrzej Kazarnowicz, Mehdi M Moezi, Marshall T Schreeder, Judy Schnyder, Ada Ao-Baslock, Ashutosh K Pathak, Mark S Berger, GEM017 Investigators
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 85 Issue 3 Pg. 420-8 (Sep 2014) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 24997137 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Indoles
• Pyrroles
• Etoposide
• Carboplatin
• obatoclax

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage)
• Comorbidity
• Etoposide (administration & dosage)
• Female
• Humans
• Indoles
• Lung Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Pyrroles (administration & dosage)
• Small Cell Lung Carcinoma (drug therapy, mortality, pathology)
• Treatment Outcome