Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer.

Abstract

BACKGROUND:

This open-label Phase III trial (NCT02264990) evaluated the PARP inhibitor, veliparib, combined with carboplatin/paclitaxel versus chemotherapy alone for first-line treatment of patients with advanced non-squamous non-small cell lung cancers (NSCLC). A 52-gene expression classifier (LP52) previously shown to identify patients more likely to respond to veliparib was evaluated as a planned correlative analysis.

MATERIALS AND METHODS:

Adult current or former smokers with advanced non-squamous NSCLC were randomized 1:1 to veliparib (120 mg daily for 7 days/cycle) with carboplatin and paclitaxel or to investigators' choice of platinum doublet chemotherapy (up to 6, 21-day cycles), with optional pemetrexed maintenance. Prospective analysis of the LP52 signature was conducted using a clinical Qiagen/HTG assay. The primary endpoint was overall survival (OS) in LP52+ patients.

RESULTS:

Overall, 595 patients received veliparib + carboplatin/paclitaxel (n = 298) or chemotherapy alone (n = 297); 13% (n = 40) in each arm were LP52+. The primary endpoint was not met; median OS was 11.2 months with veliparib + carboplatin/paclitaxel versus 9.2 months with chemotherapy alone in the LP52+ subgroup (hazard ratio [HR] 0.644, 95% confidence interval [CI]: 0.396-1.048; P = .113). In the overall population, median OS was 12.1 months in both arms (HR 0.986, 95% CI: 0.827-1.176; P = .846). No new safety signals were observed.

CONCLUSION:

In patients with non-squamous NSCLC, there was no significant improvement in OS with veliparib + carboplatin/paclitaxel versus chemotherapy alone, although a trend toward improved OS in the LP52+ population suggests this subgroup may benefit from veliparib. Statistical power was limited due to the small sample size.

• Authors: Ramaswamy Govindan, Mike Lind, Amelia Insa, Saad A Khan, Dmitry Uskov, Ali Tafreshi, Salih Guclu, Jair Bar, Terufumi Kato, Ki Hyeong Lee, Kazuhiko Nakagawa, Olfred Hansen, Bonne Biesma, Madan G Kundu, Martin Dunbar, Lei He, Peter Ansell, Vasudha Sehgal, Xin Huang, Jaimee Glasgow, Bruce A Bach
• Journal: Clinical lung cancer (Clin Lung Cancer) Vol. 23 Issue 3 Pg. 214-225 (05 2022) ISSN: 1938-0690 [Electronic] United States
• PMID: 35331641 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Benzimidazoles
• veliparib
• Carboplatin
• Paclitaxel

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Benzimidazoles
• Carboplatin
• Carcinoma, Non-Small-Cell Lung
• Humans
• Lung Neoplasms
• Paclitaxel