Τίτλος:
Veliparib in Combination With Platinum-Based Chemotherapy for First-Line
Treatment of Advanced Squamous Cell Lung Cancer: A Randomized,
Multicenter Phase III Study
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
PURPOSE Squamous non-small-cell lung cancer (sqNSCLC) is genetically
complex with evidence of DNA damage. This phase III study investigated
the efficacy and safety of poly (ADP-ribose) polymerase inhibitor
veliparib in combination with conventional chemotherapy for advanced
sqNSCLC (NCT02106546).
PATIENTS AND METHODS Patients age >= 18 years with untreated, advanced
sqNSCLC were randomly assigned 1:1 to carboplatin and paclitaxel with
veliparib 120 mg twice daily (twice a day) or placebo twice a day for up
to six cycles. The primary end point was overall survival (OS) in the
veliparib arm versus the control arm in current smokers, based on phase
II findings. Archival tumor samples were provided for biomarker analysis
using a 52-gene expression histology classifier (LP52).
RESULTS Overall, 970 patients were randomly assigned to carboplatin and
paclitaxel plus either veliparib (n = 486) or placebo (n = 484); 57%
were current smokers. There was no significant OS benefit with veliparib
in current smokers, with median OS 11.9 versus 11.1 months (hazard ratio
LHRJ, 0.905; 95% CI, 0.744 to 1.101; P = .266). In the overall
population, OS favored veliparib; median OS was 12.2 versus 11.2 months
(HR, 0.853; 95% CI, 0.747 to 0.974), with no difference in
progression-free survival (median 5.6 months per arm). In patients with
biomarker-evaluable tumor samples (n = 360), OS favored veliparib in the
LP52-positive population (median 14.0 v 9.6 months; HR, 0.66; 95% CI,
0.49 to 0.89), but favored placebo in the LP52-negative population
(median 11.0 v 14.4 months; HR, 1.33; 95% CI, 0.95 to 1.86). No new
safety signals were observed in the experimental arm.
CONCLUSION In current smokers with advanced sqNSCLC, there was no
therapeutic benefit of adding veliparib to first-line chemotherapy. The
LP52 signature may identify a subgroup of patients likely to derive
benefit from veliparib with chemotherapy. (C) 2021 by American Society
of Clinical Oncology
Συγγραφείς:
Ramalingam, Suresh S.
Novello, Silvia
Guclu, Salih Zeki and
Bentsion, Dmitry
Zvirbule, Zanete
Szilasi, Maria
Bernabe,
Reyes
Syrigos, Konstantinos
Byers, Lauren Averett
Clingan,
Philip
Bar, Jair
Vokes, Everett E.
Govindan, Ramaswamy and
Dunbar, Martin
Ansell, Peter
He, Lei
Huang, Xin
Sehgal,
Vasudha
Glasgow, Jaimee
Bach, Bruce A.
Mazieres, Julien
Περιοδικό:
Journal of Clinical Oncology
Εκδότης:
Lippincott, Williams & Wilkins
DOI:
10.1200/JCO.20.03318
