Corey J Langer1, Istvan Albert2, Helen J Ross3, Peter Kovacs4, L Johnetta Blakely5, Gabor Pajkos6, Attila Somfay7, Petr Zatloukal8, Andrzej Kazarnowicz9, Mehdi M Moezi10, Marshall T Schreeder11, Judy Schnyder12, Ada Ao-Baslock13, Ashutosh K Pathak14, Mark S Berger12. 1. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: corey.langer@uphs.upenn.edu. 2. Mátrai Gyógyintézet, Mátraháza, Hungary. 3. Mayo Clinic, Scottsdale, AZ, United States. 4. University of Debrecen, Debrecen, Hungary. 5. The West Clinic, Memphis, TN, United States. 6. Bacs-Kiskun County Hospital, Kecskemét, Hungary. 7. University of Szeged, Szeged, Hungary. 8. Charles University, Faculty Hospital Bulovka and Postgraduate Medical Institute, Prague, Czech Republic. 9. Tuberculosis and Lung Disease Hospital, Olsztyn, Poland. 10. Cancer Specialists of North Florida, Jacksonville, FL, United States. 11. Clearview Cancer Institute, Huntsville, AL, United States. 12. Gemin X Pharmaceuticals, Malvern, PA, United States. 13. Powered 4 Significance LLC, Bloomsbury, NJ, United States. 14. Teva Pharmaceuticals, Frazer, PA, United States.
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 withCbEOb (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.
RCT Entities:
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: Mariacarmela Santarpia; Maria Grazia Daffinà; Niki Karachaliou; Maria González-Cao; Chiara Lazzari; Giuseppe Altavilla; Rafael Rosell Journal: Transl Lung Cancer Res Date: 2016-02