Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study.

Abstract

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 [HR], 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.

• Authors: Suresh S Ramalingam, Silvia Novello, Salih Zeki Guclu, Dmitry Bentsion, Zanete Zvirbule, Maria Szilasi, Reyes Bernabe, Konstantinos Syrigos, Lauren Averett Byers, Philip Clingan, Jair Bar, Everett E Vokes, Ramaswamy Govindan, Martin Dunbar, Peter Ansell, Lei He, Xin Huang, Vasudha Sehgal, Jaimee Glasgow, Bruce A Bach, Julien Mazieres
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 39 Issue 32 Pg. 3633-3644 (11 10 2021) ISSN: 1527-7755 [Electronic] United States
• PMID: 34436928 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Biomarkers, Tumor
• veliparib
• Carboplatin
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Benzimidazoles (adverse effects, therapeutic use)
• Biomarkers, Tumor (genetics)
• Carboplatin (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, mortality, secondary)
• Carcinoma, Squamous Cell (drug therapy, genetics, mortality, secondary)
• Clinical Decision-Making
• Female
• Gene Expression Profiling
• Humans
• Lung Neoplasms (drug therapy, genetics, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Paclitaxel (adverse effects, therapeutic use)
• Patient Selection
• Progression-Free Survival
• Smokers
• Time Factors
• Transcriptome