A Dose-finding Study Followed by a Phase II Randomized, Placebo-controlled Trial of Chemoradiotherapy With or Without Veliparib in Stage III Non–small-cell Lung Cancer: SWOG 1206 (8811)

We conducted a 2-part study to evaluate the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy (CRT) for stage III non–small-cell lung cancer. In the phase I part, patients were treated successively at 3 dose levels of veliparib (40, 80, and 120 mg) twice daily during CRT. In the p...

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Published in:Clinical lung cancer 2021-07, Vol.22 (4), p.313-323.e1
Main Authors: Argiris, Athanassios, Miao, Jieling, Cristea, Mihaela C., Chen, Allen M., Sands, Jacob M., Decker, Roy H., Gettinger, Scott N., Daly, Megan E., Faller, Bryan A., Albain, Kathy S., Yanagihara, Ronald H., Garland, Linda L., Byers, Lauren A., Wang, Ding, Koczywas, Marianna, Redman, Mary W., Kelly, Karen, Gandara, David R.
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Benzimidazoles - administration & dosage
carboplatin
Carboplatin - administration & dosage
Carcinoma, Non-Small-Cell Lung - pathology
Carcinoma, Non-Small-Cell Lung - therapy
Chemoradiotherapy - methods
Dose-Response Relationship, Drug
Female
Humans
Lung Neoplasms - pathology
Lung Neoplasms - therapy
Male
Middle Aged
Neoplasm Staging
NSCLC
paclitaxel
Paclitaxel - administration & dosage
PARP inhibitors
Progression-Free Survival
Survival Rate
Thoracic radiotherapy
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Summary:We conducted a 2-part study to evaluate the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy (CRT) for stage III non–small-cell lung cancer. In the phase I part, patients were treated successively at 3 dose levels of veliparib (40, 80, and 120 mg) twice daily during CRT. In the phase II part, patients were randomized to receive veliparib or placebo during thoracic radiotherapy with concurrent weekly carboplatin and paclitaxel, followed by 2 cycles of consolidation carboplatin and paclitaxel with veliparib or placebo. The study was prematurely discontinued owing to the emergence of adjuvant immunotherapy as standard of care. Of 21 patients enrolled in phase I, 2 patients developed dose-limiting toxicities (DLTs): 1 grade 3 esophagitis with dysphagia (at 40 mg) and 1 grade 3 esophagitis with dehydration (at 80 mg). No DLTs were seen at veliparib dose of 120 mg twice daily, which was selected for the phase II part that enrolled 31 eligible patients. Progression-free survival (PFS) was not different between the 2 arms (P = .20). For the veliparib and placebo arms, response rates were 56% and 69%, PFS at 1 year 47% and 46%, and overall survival at 1 year 89% and 54%, respectively. Veliparib with CRT was feasible and well tolerated. Efficacy could not accurately be determined because of early study closure. Nonetheless, there is enthusiasm for the evaluation of PARP inhibitors in lung cancer as predictive biomarkers are being developed and combinations with immunotherapy are attractive. We evaluated the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy with carboplatin and paclitaxel for stage III non–small-cell lung cancer. In the phase I part that enrolled 21 patients we selected veliparib dose of 120 mg twice daily as the recommended phase II dose. The phase II part enrolled 31 eligible patients. Progression-free survival was not different between the 2 arms (P = .20). Veliparib with chemoradiotherapy was feasible and well tolerated. Efficacy could not be accurately determined because of early study closure.
ISSN:1525-7304
1938-0690
DOI:10.1016/j.cllc.2021.02.009