Randomized Phase II Trial of Cisplatin and Etoposide in Combination With Veliparib or Placebo for Extensive-Stage Small-Cell Lung Cancer: ECOG-ACRIN 2511 Study

• Type of Material: Article
• Authors: Taofeek K Owonikoko, Emory University; Suzanne E. Dahlberg, Dana Farber Cancer Institute; Gabriel Sica, Emory University; Lynne I. Wagner, Northwestern University; James L. Wade, III, Decatur Memorial Hospital; Gordan Srkalovic, Sparrow Regional Cancer Center; Bradley W. Lash, Guthrie Clinic-Robert Packer Hospital; Joseph W. Leach, Metro Minnesota National Cancer Institute Community Oncology Research Program; Ticiana B. Leal, University of Wisconsin; Suresh S Ramalingam, Emory University
• Language: English
• Date: 2019-01-20
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2018 by American Society of Clinical Oncology.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.18.00264
• Title of Journal or Parent Work: Journal of Clinical Oncology
• ISSN: 0732-183X
• Volume: 37
• Issue: 3
• Start Page: 222
• End Page: +
• Grant/Funding Information: This study was coordinated by the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group (Peter J. O'Dwyer, MD; and Mitchell D. Schnall, MD, PhD, group cochairs); and supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH; Grants No. CA180820; CA180794; CA180864; CA189828; CA189830; CA189971; CA180790; CA189863; and CA180799); and by NIH/NCI Grant No 1K23CA164015 to T.K.O.
• Keywords: IRINOTECAN/CISPLATIN; Science & Technology; OLAPARIB; Oncology; GERMLINE BRCA1; MUTATION; PARP INHIBITOR VELIPARIB; Life Sciences & Biomedicine; BEVACIZUMAB; ETOPOSIDE/CISPLATIN; CARBOPLATIN; RUCAPARIB; CHEMOTHERAPY
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology

Abstract

PURPOSE Veliparib, a poly (ADP ribose) polymerase inhibitor, potentiated standard chemotherapy against small-cell lung cancer (SCLC) in preclinical studies. We evaluated the combination of veliparib with cisplatin and etoposide (CE; CE+V) doublet in untreated, extensive-stage SCLC (ES-SCLC). MATERIALS AND METHODS Patients with ES-SCLC, stratified by sex and serum lactate dehydrogenase levels, were randomly assigned to receive four 3-week cycles of CE (75 mg/m 2 intravenously on day 1 and 100 mg/m 2 on days 1 through 3) along with veliparib (100 mg orally twice per day on days 1 through 7) or placebo (CE+P). The primary end point was progression-free survival (PFS). Using an overall one-sided 0.10-level log-rank test, the study had 88% power to demonstrate a 37.5% reduction in the PFS hazard rate. RESULTS A total of 128 eligible patients received treatment on protocol. The median age was 66 years, 52% of patients were men, and Eastern Cooperative Oncology Group performance status was 0 for 29% of patients and 1 for 71%. The respective median PFS for the CE+V arm versus the CE+P arm was 6.1 versus 5.5 months (unstratified hazard ratio [HR], 0.75 [one-sided P = .06]; stratified HR, 0.63 [one-sided P = .01]), favoring CE+V. The median overall survival was 10.3 versus 8.9 months (stratified HR, 0.83; 80% CI, 0.64 to 1.07; one-sided P = .17) for the CE+V and CE+P arms, respectively. The overall response rate was 71.9% versus 65.6% (two-sided P = .57) for CE+V and CE+P, respectively. There was a significant treatment-by-strata interaction in PFS: Male patients with high lactate dehydrogenase levels derived significant benefit (PFS HR, 0.34; 80% CI, 0.22 to 0.51) but there was no evidence of benefit among patients in other strata (PFS HR, 0.81; 80% CI, 0.60 to 1.09). The following grade $ 3 hematology toxicities were more frequent in the CE+V arm than the CE+P arm: CD4 lymphopenia (8% v 0%; P = .06) and neutropenia (49% v 32%; P = .08), but treatment delivery was comparable. CONCLUSION The addition of veliparib to frontline chemotherapy showed signal of efficacy in patients with ES-SCLC and the study met its prespecified end point.