PMID- 34311345 OWN - NLM STAT- MEDLINE DCOM- 20210823 LR - 20221221 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 159 DP - 2021 Sep TI - Veliparib in combination with carboplatin/paclitaxel-based chemoradiotherapy in patients with stage III non-small cell lung cancer. PG - 56-65 LID - S0169-5002(21)00459-1 [pii] LID - 10.1016/j.lungcan.2021.06.028 [doi] AB - OBJECTIVES: Veliparib is a potent poly(ADP)-ribose polymerase (PARP) 1 and 2 inhibitor that impedes repair of DNA damage induced by cytotoxic and radiation therapies. This phase 1 study evaluated veliparib in combination with chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients received veliparib orally twice daily (BID) in escalating doses (60-240 mg, Day -3 to 1 day after last dose of radiation) combined with weekly carboplatin (area under the curve [AUC] 2 mg/mL/min), paclitaxel (45 mg/m(2)), and daily radiation therapy (60 Gy in 30 fractions), followed by two cycles of veliparib (120-240 mg BID, Days -2 through 5 of each 21-day cycle), carboplatin (AUC 6 mg/mL/min, Day 1 of each cycle), and paclitaxel (200 mg/m(2), Day 1 of each cycle) consolidation. Endpoints included veliparib maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), pharmacokinetics, safety, and efficacy. RESULTS: Forty-eight patients were enrolled. The MTD/RP2D of veliparib was 240 mg BID with chemoradiotherapy followed by 120 mg BID with consolidation. The most common any-grade adverse events (AEs) in this cohort for the whole treatment period were nausea (83%), esophagitis (75%), neutropenia (75%), and thrombocytopenia (75%). Dose-proportional pharmacokinetics of veliparib were observed. Median progression-free survival (mPFS) was 19.6 months (95% CI: 9.7-32.6). Median overall survival was estimated to be 32.6 months (95% CI: 15.0-not reached). In patients treated with the RP2D, mPFS was 19.6 months (95% CI: 3.0-not reached). CONCLUSIONS: When combined with standard concurrent chemoradiotherapy and consolidation chemotherapy in patients with stage III NSCLC, veliparib demonstrated an acceptable safety profile and antitumor activity with an mPFS of 19.6 months. CI - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Kozono, David E AU - Kozono DE AD - Department of Radiation Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Electronic address: dkozono@bwh.harvard.edu. FAU - Stinchcombe, Thomas E AU - Stinchcombe TE AD - Duke Cancer Institute, Durham, 2 Seeley Mudd, 10 Bryan Searle Drive, Durham, NC 27710, USA. Electronic address: thomas.stinchcombe@duke.edu. FAU - Salama, Joseph K AU - Salama JK AD - Duke Cancer Institute, Durham, 2 Seeley Mudd, 10 Bryan Searle Drive, Durham, NC 27710, USA. Electronic address: joseph.salama@duke.edu. FAU - Bogart, Jeffrey AU - Bogart J AD - Department of Radiation Oncology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. Electronic address: bogartj@upstate.edu. FAU - Petty, W Jeffrey AU - Petty WJ AD - Department of Hematology and Oncology, Wake Forest School of Medicine, Bowman Gray Center for Medical Education, 475 Vine Street, Winston-Salem, NC 27101, USA. Electronic address: wpetty@wakehealth.edu. FAU - Guarino, Michael J AU - Guarino MJ AD - Christiana Care Health System, Helen F Graham Cancer Center, 4701 Ogletown Stanton Road, Suite 3400, Newark, DE 19713, USA. Electronic address: Michael.Guarino@usoncology.com. FAU - Bazhenova, Lyudmila AU - Bazhenova L AD - Department of Medicine, Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: lbazhenova@ucsd.edu. FAU - Larner, James M AU - Larner JM AD - University of Virginia, Emily Couric Clinical Cancer Center, 1240 Lee Street, Charlottesville, VA 22903, USA. Electronic address: JML2P@hscmail.mcc.virginia.edu. FAU - Weiss, Jared AU - Weiss J AD - Lineberger Comprehensive Cancer Center at the University of North Carolina, Cancer Hospital, 101 Manning Drive, Chapel Hill, NC 27514, USA. Electronic address: jared_weiss@med.unc.edu. FAU - DiPetrillo, Thomas A AU - DiPetrillo TA AD - Department of Radiation Oncology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA. Electronic address: TDiPetrillo@Lifespan.org. FAU - Feigenberg, Steven J AU - Feigenberg SJ AD - Greenebaum Comprehensive Cancer Center, University of Maryland, 22 South Greene Street, Baltimore, MD 21201, USA. FAU - Chen, Xin AU - Chen X AD - Data and Statistical Sciences, AbbVie Inc, 1 N. Waukegan Road, North Chicago, IL 60064, USA. Electronic address: xin.chen@abbvie.com. FAU - Sun, Zhaowen AU - Sun Z AD - Data and Statistical Sciences, AbbVie Inc, 1 N. Waukegan Road, North Chicago, IL 60064, USA. Electronic address: zhaowen.sun@abbvie.com. FAU - Nuthalapati, Silpa AU - Nuthalapati S AD - Clinical Pharmacology and Pharmacometrics, AbbVie Inc, 1 N. Waukegan Road, North Chicago, IL 60064, USA. Electronic address: silpa.nuthalapati@Abbvie.com. FAU - Rosenwinkel, Lindsey AU - Rosenwinkel L AD - Global Pharmaceutical R&D, AbbVie Inc, 1 N. Waukegan Road, North Chicago, IL 60064, USA. Electronic address: lindsey.rosenwinkel@abbvie.com. FAU - Johnson, Eric F AU - Johnson EF AD - Oncology Early Development, AbbVie Inc, 1 N. Waukegan Road, North Chicago, IL 60064, USA. Electronic address: eric.f.johnson@abbvie.com. FAU - Bach, Bruce A AU - Bach BA AD - Oncology Development, AbbVie Inc, 1 N. Waukegan Road, North Chicago, IL 60064, USA. Electronic address: bruce.bach@abbvie.com. FAU - Luo, Yan AU - Luo Y AD - Oncology Development, AbbVie Inc, 1 N. Waukegan Road, North Chicago, IL 60064, USA. Electronic address: yan.luo@abbvie.com. FAU - Vokes, Everett E AU - Vokes EE AD - Department of Medicine, University of Chicago, 5801 South Ellis Avenue, Chicago, IL 60637, USA. Electronic address: evokes@medicine.bsd.uchicago.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210721 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Benzimidazoles) RN - 01O4K0631N (veliparib) RN - BG3F62OND5 (Carboplatin) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Benzimidazoles MH - Carboplatin/therapeutic use MH - *Carcinoma, Non-Small-Cell Lung/drug therapy MH - Chemoradiotherapy MH - Humans MH - *Lung Neoplasms/drug therapy MH - Paclitaxel/therapeutic use OTO - NOTNLM OT - Chemoradiotherapy OT - Lung neoplasms OT - Non-small cell OT - Phase 1 OT - Veliparib EDAT- 2021/07/27 06:00 MHDA- 2021/08/24 06:00 CRDT- 2021/07/26 20:25 PHST- 2021/01/29 00:00 [received] PHST- 2021/06/10 00:00 [revised] PHST- 2021/06/21 00:00 [accepted] PHST- 2021/07/27 06:00 [pubmed] PHST- 2021/08/24 06:00 [medline] PHST- 2021/07/26 20:25 [entrez] AID - S0169-5002(21)00459-1 [pii] AID - 10.1016/j.lungcan.2021.06.028 [doi] PST - ppublish SO - Lung Cancer. 2021 Sep;159:56-65. doi: 10.1016/j.lungcan.2021.06.028. Epub 2021 Jul 21.