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.
Publication/Presentation Date
1-20-2019
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
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.
Volume
37
Issue
3
First Page
222
Last Page
229
ISSN
1527-7755
Published In/Presented At
Owonikoko, T. K., Dahlberg, S. E., Sica, G. L., Wagner, L. I., Wade, J. L., 3rd, Srkalovic, G., Lash, B. W., Leach, J. W., Leal, T. B., Aggarwal, C., & Ramalingam, S. S. (2019). 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 37(3), 222–229. https://doi.org/10.1200/JCO.18.00264
Disciplines
Medicine and Health Sciences | Oncology
PubMedID
30523756
Peer Reviewed for front end display
Peer-Reviewed
Department(s)
Department of Medicine, Hematology-Medical Oncology Division, Department of Medicine Faculty
Document Type
Article