TY - JOUR
T1 - Veliparib in Combination With Platinum- Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer
T2 - A Randomized, Multicenter Phase III Study
AU - Ramalingam, Suresh S.
AU - Novello, Silvia
AU - Guclu, Salih Zeki
AU - Bentsion, Dmitry
AU - Zvirbule, Zanete
AU - Szilasi, Maria
AU - Bernabe, Reyes
AU - Syrigos, Konstantinos
AU - Byers, Lauren Averett
AU - Clingan, Philip
AU - Bar, Jair
AU - Vokes, Everett E.
AU - Govindan, Ramaswamy
AU - Dunbar, Martin
AU - Ansell, Peter
AU - He, Lei
AU - Huang, Xin
AU - Sehgal, Vasudha
AU - Glasgow, Jaimee
AU - Bach, Bruce A.
AU - Mazieres, Julien
N1 - Publisher Copyright:
© 2021 American Society of Clinical Oncology. All rights reserved.
PY - 2021/11/10
Y1 - 2021/11/10
N2 - 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 (n5486) or placebo (n5484); 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 5 .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 5 360), 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.
AB - 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 (n5486) or placebo (n5484); 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 5 .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 5 360), 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.
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U2 - 10.1200/JCO.20.03318
DO - 10.1200/JCO.20.03318
M3 - Article
C2 - 34436928
AN - SCOPUS:85121949640
SN - 0732-183X
VL - 39
SP - 3633
EP - 3644
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 32
ER -