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Veliparib in combination with carboplatin/paclitaxel-based chemoradiotherapy in patients with stage III non-small cell lung cancer.

Publication ,  Journal Article
Kozono, DE; Stinchcombe, TE; Salama, JK; Bogart, J; Petty, WJ; Guarino, MJ; Bazhenova, L; Larner, JM; Weiss, J; DiPetrillo, TA; Feigenberg, SJ ...
Published in: Lung Cancer
September 2021

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/m2), 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/m2, 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.

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Published In

Lung Cancer

DOI

EISSN

1872-8332

Publication Date

September 2021

Volume

159

Start / End Page

56 / 65

Location

Ireland

Related Subject Headings

  • Paclitaxel
  • Oncology & Carcinogenesis
  • Lung Neoplasms
  • Humans
  • Chemoradiotherapy
  • Carcinoma, Non-Small-Cell Lung
  • Carboplatin
  • Benzimidazoles
  • Antineoplastic Combined Chemotherapy Protocols
  • 3211 Oncology and carcinogenesis
 

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Kozono, D. E., Stinchcombe, T. E., Salama, J. K., Bogart, J., Petty, W. J., Guarino, M. J., … Vokes, E. E. (2021). Veliparib in combination with carboplatin/paclitaxel-based chemoradiotherapy in patients with stage III non-small cell lung cancer. Lung Cancer, 159, 56–65. https://doi.org/10.1016/j.lungcan.2021.06.028
Kozono, David E., Thomas E. Stinchcombe, Joseph K. Salama, Jeffrey Bogart, W Jeffrey Petty, Michael J. Guarino, Lyudmila Bazhenova, et al. “Veliparib in combination with carboplatin/paclitaxel-based chemoradiotherapy in patients with stage III non-small cell lung cancer.Lung Cancer 159 (September 2021): 56–65. https://doi.org/10.1016/j.lungcan.2021.06.028.
Kozono DE, Stinchcombe TE, Salama JK, Bogart J, Petty WJ, Guarino MJ, et al. Veliparib in combination with carboplatin/paclitaxel-based chemoradiotherapy in patients with stage III non-small cell lung cancer. Lung Cancer. 2021 Sep;159:56–65.
Kozono, David E., et al. “Veliparib in combination with carboplatin/paclitaxel-based chemoradiotherapy in patients with stage III non-small cell lung cancer.Lung Cancer, vol. 159, Sept. 2021, pp. 56–65. Pubmed, doi:10.1016/j.lungcan.2021.06.028.
Kozono DE, Stinchcombe TE, Salama JK, Bogart J, Petty WJ, Guarino MJ, Bazhenova L, Larner JM, Weiss J, DiPetrillo TA, Feigenberg SJ, Chen X, Sun Z, Nuthalapati S, Rosenwinkel L, Johnson EF, Bach BA, Luo Y, Vokes EE. Veliparib in combination with carboplatin/paclitaxel-based chemoradiotherapy in patients with stage III non-small cell lung cancer. Lung Cancer. 2021 Sep;159:56–65.
Journal cover image

Published In

Lung Cancer

DOI

EISSN

1872-8332

Publication Date

September 2021

Volume

159

Start / End Page

56 / 65

Location

Ireland

Related Subject Headings

  • Paclitaxel
  • Oncology & Carcinogenesis
  • Lung Neoplasms
  • Humans
  • Chemoradiotherapy
  • Carcinoma, Non-Small-Cell Lung
  • Carboplatin
  • Benzimidazoles
  • Antineoplastic Combined Chemotherapy Protocols
  • 3211 Oncology and carcinogenesis