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

Autor: Govindan R; Washington University School of Medicine, St. Louis, MO. Electronic address: rgovindan@wustl.edu., Lind M; Hull York Medical School, University Rd, York, UK., Insa A; Hospital Clínico Universitario de Valencia, Valencia, Spain., Khan SA; University of Texas Southwestern Medical Center, Dallas, TX., Uskov D; Moscow Regional Oncology Dispensary, Balashikha, Russian Federation., Tafreshi A; Wollongong Private Hospital and Wollongong Oncology, Wollongong, Australia., Guclu S; Chest Diseases Clinic, Izmir Chest Diseases Research Hospital, Dr Suat Seren Göğüs Hastalıkları ve Cerrahisi Eğitim ve Araştırma Hastanesi, Izmir, Turkey., Bar J; Institute of Oncology, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel., Kato T; Kanagawa Cancer Center, Yokohama, Kanagawa, Japan., Lee KH; Chungbuk National University Hospital, Chungcheongbuk-Do, Republic of Korea., Nakagawa K; Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan., Hansen O; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Odense University Hospital, Odense, Denmark., Biesma B; Jeroen Bosch Hospital, GZ's -Hertogenbosch, Netherlands., Kundu MG; AbbVie Inc, North Chicago, IL., Dunbar M; AbbVie Inc, North Chicago, IL., He L; AbbVie Inc, North Chicago, IL., Ansell P; AbbVie Inc, North Chicago, IL., Sehgal V; AbbVie Inc, North Chicago, IL., Huang X; AbbVie Inc, North Chicago, IL., Glasgow J; AbbVie Inc, North Chicago, IL., Bach BA; AbbVie Inc, North Chicago, IL.
Jazyk: angličtina
Zdroj: Clinical lung cancer [Clin Lung Cancer] 2022 May; Vol. 23 (3), pp. 214-225. Date of Electronic Publication: 2022 Feb 04.
DOI: 10.1016/j.cllc.2022.01.005
Abstrakt: 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.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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