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)

被引:19
作者
Argiris, Athanassios [1 ,2 ]
Miao, Jieling [3 ,4 ]
Cristea, Mihaela C. [5 ]
Chen, Allen M. [6 ,7 ]
Sands, Jacob M. [8 ,9 ]
Decker, Roy H. [10 ]
Gettinger, Scott N. [10 ]
Daly, Megan E. [11 ]
Faller, Bryan A. [12 ]
Albain, Kathy S. [13 ]
Yanagihara, Ronald H. [14 ]
Garland, Linda L. [15 ]
Byers, Lauren A. [16 ]
Wang, Ding [17 ]
Koczywas, Marianna [5 ]
Redman, Mary W. [3 ,4 ]
Kelly, Karen [11 ]
Gandara, David R. [11 ]
机构
[1] Hygeia Hosp, Athens, Greece
[2] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA
[3] SWOG Stat & Data Management Ctr, Seattle, WA USA
[4] Fred Hutchinson Canc Res Ctr, Seattle, WA USA
[5] City Hope Natl Med Ctr, Duarte, CA USA
[6] Univ Kansas, Kansas City, KS USA
[7] Univ Calif Irvine, Irvine, CA USA
[8] Lahey Hosp Med Ctr, Burlington, MA USA
[9] Dana Farber Canc Inst, Boston, MA USA
[10] Yale Univ, New Haven, CT USA
[11] Univ Calif Davis, Sacramento, CA USA
[12] Heartland NCORP Missouri Baptist Med Ctr, St Louis, MO USA
[13] Loyola Univ, Chicago Stritch Sch Med, Maywood, IL USA
[14] Hawaii MU NCORP Straub Clin Hosp, Honolulu, HI USA
[15] Univ Arizona, Tucson, AZ USA
[16] MD Anderson Canc Ctr, Houston, TX USA
[17] Henry Ford Hosp, Detroit, MI USA
基金
美国国家卫生研究院;
关键词
NSCLC; Thoracic radiotherapy; PARP inhibitors; carboplatin; paclitaxel; IN-VIVO; RADIOTHERAPY; CARBOPLATIN; PACLITAXEL; CONCURRENT; RADIATION; INHIBITOR; CISPLATIN; ETOPOSIDE;
D O I
10.1016/j.cllc.2021.02.009
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. Background: 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. Patients and Methods: 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 velipar ib or placebo dur ing 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. Results: 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. Conclusion: 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.
引用
收藏
页码:313 / +
页数:12
相关论文
共 23 条
[1]   Clinical Development of Novel Drug-Radiotherapy Combinations [J].
Ahmad, Saif S. ;
Crittenden, Marka R. ;
Tran, Phuoc T. ;
Kluetz, Paul G. ;
Blumenthal, Gideon M. ;
Bulbeck, Helen ;
Baird, Richard D. ;
Williams, Kaye J. ;
Illidge, Tim ;
Hahn, Stephen M. ;
Lawrence, Theodore S. ;
Spears, Patricia A. ;
Walker, Amanda J. ;
Sharma, Ricky A. .
CLINICAL CANCER RESEARCH, 2019, 25 (05) :1455-1461
[2]   Inhibition of poly (ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models [J].
Albert, Jeffrey M. ;
Cao, Carolyn ;
Kim, Kwang Woon ;
Willey, Christopher D. ;
Geng, Ling ;
Xiao, Dakai ;
Wang, Hong ;
Sandler, Alan ;
Johnson, David H. ;
Colevas, Alexander D. ;
Low, Jennifer ;
Rothenberg, Mace L. ;
Lu, Bo .
CLINICAL CANCER RESEARCH, 2007, 13 (10) :3033-3042
[3]   Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer [J].
Antonia, S. J. ;
Villegas, A. ;
Daniel, D. ;
Vicente, D. ;
Murakami, S. ;
Hui, R. ;
Yokoi, T. ;
Chiappori, A. ;
Lee, K. H. ;
de Wit, M. ;
Cho, B. C. ;
Bourhaba, M. ;
Quantin, X. ;
Tokito, T. ;
Mekhail, T. ;
Planchard, D. ;
Kim, Y. -C. ;
Karapetis, C. S. ;
Hiret, S. ;
Ostoros, G. ;
Kubota, K. ;
Gray, J. E. ;
Paz-Ares, L. ;
de Castro Carpeno, J. ;
Wadsworth, C. ;
Melillo, G. ;
Jiang, H. ;
Huang, Y. ;
Dennis, P. A. ;
Ozguroglu, M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (20) :1919-1929
[4]   Phase 1 study of veliparib (ABT-888), a poly (ADP-ribose) polymerase inhibitor, with carboplatin and paclitaxel in advanced solid malignancies [J].
Appleman, Leonard J. ;
Beumer, Jan H. ;
Jiang, Yixing ;
Lin, Yan ;
Ding, Fei ;
Puhalla, Shannon ;
Swartz, Leigh ;
Owonikoko, Taofeek K. ;
Harvey, R. Donald ;
Stoller, Ronald ;
Petro, Daniel P. ;
Tawbi, Hussein A. ;
Argiris, Athanassios ;
Strychor, Sandra ;
Pouquet, Marie ;
Kiesel, Brian ;
Chen, Alice P. ;
Gandara, David ;
Belani, Chandra P. ;
Chu, Edward ;
Ramalingam, Suresh S. .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2019, 84 (06) :1289-1301
[5]   Meta-Analysis of Concomitant Versus Sequential Radiochemotherapy in Locally Advanced Non-Small-Cell Lung Cancer [J].
Auperin, Anne ;
Le Pechoux, Cecile ;
Rolland, Estelle ;
Curran, Walter J. ;
Furuse, Kiyoyuki ;
Fournel, Pierre ;
Belderbos, Jose ;
Clamon, Gerald ;
Ulutin, Hakki Cuneyt ;
Paulus, Rebecca ;
Yamanaka, Takeharu ;
Bozonnat, Marie-Cecile ;
Uitterhoeve, Apollonia ;
Wang, Xiaofei ;
Stewart, Lesley ;
Arriagada, Rodrigo ;
Burdett, Sarah ;
Pignon, Jean-Pierre .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (13) :2181-2190
[6]   Evaluation of poly (ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma [J].
Barazzuol, Lara ;
Jena, Raj ;
Burnet, Neil G. ;
Meira, Lisiane B. ;
Jeynes, Jonathan C. G. ;
Kirkby, Karen J. ;
Kirkby, Norman F. .
RADIATION ONCOLOGY, 2013, 8
[7]   Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study [J].
Bradley, Jeffrey D. ;
Paulus, Rebecca ;
Komaki, Ritsuko ;
Masters, Gregory ;
Blumenschein, George ;
Schild, Steven ;
Bogart, Jeffrey ;
Hu, Chen ;
Forster, Kenneth ;
Magliocco, Anthony ;
Kavadi, Vivek ;
Garces, Yolanda I. ;
Narayan, Samir ;
Iyengar, Puneeth ;
Robinson, Cliff ;
Wynn, Raymond B. ;
Koprowski, Christopher ;
Meng, Joanne ;
Beitler, Jonathan ;
Gaur, Rakesh ;
Curran, Walter, Jr. ;
Choy, Hak .
LANCET ONCOLOGY, 2015, 16 (02) :187-199
[8]   Study protocols of three parallel phase 1 trials combining radical radiotherapy with the PARP inhibitor olaparib [J].
de Haan, R. ;
van Werkhoven, E. ;
van den Heuvel, M. M. ;
Peulen, H. M. U. ;
Sonke, G. S. ;
Elkhuizen, P. ;
van den Brekel, M. W. M. ;
Tesselaar, M. E. T. ;
Vens, C. ;
Schellens, J. H. M. ;
van Triest, B. ;
Verheij, M. .
BMC CANCER, 2019, 19 (01)
[9]   New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].
Eisenhauer, E. A. ;
Therasse, P. ;
Bogaerts, J. ;
Schwartz, L. H. ;
Sargent, D. ;
Ford, R. ;
Dancey, J. ;
Arbuck, S. ;
Gwyther, S. ;
Mooney, M. ;
Rubinstein, L. ;
Shankar, L. ;
Dodd, L. ;
Kaplan, R. ;
Lacombe, D. ;
Verweij, J. .
EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247
[10]   Mechanistic Dissection of PARP1 Trapping and the Impacton In Vivo Tolerability and Efficacy of PARP Inhibitors [J].
Hopkins, Todd A. ;
Shi, Yan ;
Rodriguez, Luis E. ;
Solomon, Larry R. ;
Donawho, Cherrie K. ;
DiGiammarino, Enrico L. ;
Panchal, Sanjay C. ;
Wilsbacher, Julie L. ;
Gao, Wenqing ;
Olson, Amanda M. ;
Stolarik, DeAnne F. ;
Osterling, Donald J. ;
Johnson, Eric F. ;
Maag, David .
MOLECULAR CANCER RESEARCH, 2015, 13 (11) :1465-1477