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

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 GlasgowBruce A. Bach

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)214-225
Number of pages12
JournalClinical Lung Cancer
Volume23
Issue number3
DOIs
StatePublished - May 2022

Keywords

  • Biomarkers
  • Combination therapy
  • NSCLC
  • Overall survival
  • PARP inhibitor

Fingerprint

Dive into the research topics of 'Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Patients With Advanced Non–Squamous Non–Small Cell Lung Cancer'. Together they form a unique fingerprint.

Cite this