RT Journal Article
SR Electronic
T1 Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non–Small Cell Lung Cancer
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 1937
OP 1944
DO 10.1158/1078-0432.CCR-15-3069
VO 23
IS 8
A1 Ramalingam, Suresh S.
A1 Blais, Normand
A1 Mazieres, Julien
A1 Reck, Martin
A1 Jones, C. Michael
A1 Juhasz, Erzsebet
A1 Urban, Laszlo
A1 Orlov, Sergey
A1 Barlesi, Fabrice
A1 Kio, Ebenezer
A1 Keiholz, Ulrich
A1 Qin, Qin
A1 Qian, Jiang
A1 Nickner, Caroline
A1 Dziubinski, Juliann
A1 Xiong, Hao
A1 Ansell, Peter
A1 McKee, Mark
A1 Giranda, Vincent
A1 Gorbunova, Vera
YR 2017
UL http://clincancerres.aacrjournals.org/content/23/8/1937.abstract
AB Purpose: PARP plays an important role in DNA repair. Veliparib, a PARP inhibitor, enhances the efficacy of platinum compounds and has been safely combined with carboplatin and paclitaxel. The primary endpoint of this phase II trial determined whether addition of veliparib to carboplatin and paclitaxel improved progression-free survival (PFS) in previously untreated patients with advanced/metastatic non–small cell lung cancer.Experimental Design: Patients were randomized 2:1 to carboplatin and paclitaxel with either veliparib or placebo. Veliparib (120 mg) or placebo was given on days 1 to 7 of each 3-week cycle, with carboplatin (AUC = 6 mg/mL/min) and paclitaxel (200 mg/m2) administered on day 3, for a maximum of 6 cycles.Results: Overall, 158 were included (median age, 63 years; male 68%, squamous histology 48%). Median PFS was 5.8 months in the veliparib group versus 4.2 months in the placebo group [HR, 0.72; 95% confidence interval (CI), 0.45–1.15; P = 0.17)]. Median overall survival (OS) was 11.7 and 9.1 months in the veliparib and placebo groups, respectively (HR, 0.80; 95% CI, 0.54–1.18; P = 0.27). In patients with squamous histology, median PFS (HR, 0.54; 95% CI, 0.26–1.12; P = 0.098) and OS (HR, 0.73; 95% CI, 0.43–1.24; P = 0.24) favored veliparib treatment. Objective response rate was similar between groups (veliparib: 32.4%; placebo: 32.1%), but duration of response favored veliparib treatment (HR, 0.47; 95% CI, 0.16–1.42; P = 0.18). Grade III/IV neutropenia, thrombocytopenia, and anemia were comparable between groups.Conclusions: Veliparib combination with carboplatin and paclitaxel was well-tolerated and demonstrated a favorable trend in PFS and OS versus chemotherapy alone. Patients with squamous histology had the best outcomes with veliparib combination. Clin Cancer Res; 23(8); 1937–44. ©2016 AACR.