Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non-Small Cell Lung Cancer.
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.
Emory University, Winship Cancer Center, Atlanta, Georgia. ssramal@emory.edu.
Suresh S
SS
Ramalingam
CHUM - Hôpital Notre-Dame, Montreal, Canada.
Normand
N
Blais
Larrey Hospital - CHU Toulouse, Toulouse, France.
Julien
J
Mazieres
LungenClinic Grosshansdorf, Airway Research Center North (ARCN), member of the German center for lung research (DZL), Grosshansdorf, Germany.
Martin
M
Reck
The Jones Clinic, New Albany, Mississippi.
C Michael
CM
Jones
Országos Koranvi TBC és Pulmonologiai Intézet, Budapest, Hungary.
Erzsebet
E
Juhasz
Mátra Gyógyintézet, Mátraháza, Hungary.
Laszlo
L
Urban
Pavlov Medical University, St Petersburg, Russia.
Sergey
S
Orlov
Aix Marseille University; Assistance Publique Hôpitaux de Marseille, Marseille, France.
Fabrice
F
Barlesi
IU Health Goshen Center for Cancer Care, Goshen, Indiana.
Ebenezer
E
Kio
Charité, Berlin, Germany.
Ulrich
U
Keiholz
AbbVie Inc., North Chicago, Illinois.
Qin
Q
Qin
AbbVie Inc., North Chicago, Illinois.
Jiang
J
Qian
AbbVie Inc., Saint Laurent, Quebec, Canada.
Caroline
C
Nickner
AbbVie Inc., North Chicago, Illinois.
Juliann
J
Dziubinski
AbbVie Inc., North Chicago, Illinois.
Hao
H
Xiong
AbbVie Inc., North Chicago, Illinois.
Peter
P
Ansell
AbbVie Inc., North Chicago, Illinois.
Mark
M
McKee
AbbVie Inc., North Chicago, Illinois.
Vincent
V
Giranda
Institution of Russian Academy of Medical Science, Russian Oncological Research Center, Moscow, Russia.
Vera
V
Gorbunova
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D016896:Treatment Outcome
D001562:Benzimidazoles; C521013:veliparib; D016190:Carboplatin; D017239:Paclitaxel