Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study
| العنوان: | Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer: randomized phase II study |
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| المؤلفون: | Shannon Puhalla, M. Friedlander, Igor Bondarenko, Caroline Nickner, Qin Qin, Steven J. Isakoff, Paul K. Marcom, M. Campone, Erik Jakobsen, Judy Garber, E. Chmielowska, M Palácová, Christine K. Ratajczak, H.S. Han, William J. Gradishar, Melinda L. Telli, Mark E. Robson, Jane Qian, Agnes Jager, Susan M. Domchek, D Citrin, Virginia G. Kaklamani, Yaroslav Shparyk, Stacie Peacock Shepherd, Bella Kaufman, Véronique Diéras |
| المساهمون: | Medical Oncology |
| المصدر: | Annals of Oncology, 29(1), 154-161. Elsevier Ltd. Han, H S, Diéras, V, Robson, M, Palácová, M, Marcom, P K, Jager, A, Bondarenko, I, Citrin, D, Campone, M, Telli, M L, Domchek, S M, Friedlander, M, Kaufman, B, Garber, J E, Shparyk, Y, Chmielowska, E, Jakobsen, E H, Kaklamani, V, Gradishar, W, Ratajczak, C K, Nickner, C, Qin, Q, Qian, J, Shepherd, S P, Isakoff, S J & Puhalla, S 2018, ' Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic breast cancer : Randomized phase II study ', Annals of Oncology, vol. 29, no. 1, pp. 154-161 . https://doi.org/10.1093/annonc/mdx505 |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Male, medicine.medical_treatment, Genes, BRCA2, Genes, BRCA1, Phases of clinical research, Placebos, chemistry.chemical_compound, 0302 clinical medicine, Single-Blind Method, Neoplasm Metastasis, PARP inhibitors, Benzimidazoles/administration & dosage, Temozolomide/administration & dosage, Hematology, Middle Aged, Metastatic breast cancer, Chemotherapy regimen, Neoplasm Recurrence, Local/drug therapy, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Veliparib, 03 medical and health sciences, Young Adult, Breast cancer, Breast Neoplasms/drug therapy, SDG 3 - Good Health and Well-being, Internal medicine, Paclitaxel/administration & dosage, medicine, Temozolomide, Humans, Germ-Line Mutation, Platinum, Aged, Chemotherapy, business.industry, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Carboplatin/administration & dosage, Breast Neoplasms, Male/drug therapy, medicine.disease, Carboplatin, 030104 developmental biology, chemistry, business |
| الوصف: | Background: Homologous recombination defects in BRCA1/2-mutated tumors result in sensitivity to poly(ADP-ribose) polymerase inhibitors, which interfere with DNA damage repair. Veliparib, a potent poly(ADP-ribose) polymerase inhibitor, enhanced the antitumor activity of platinum agents and temozolomide in early phase clinical trials. This phase II study examined the safety and efficacy of intermittent veliparib with carboplatin/paclitaxel (VCP) or temozolomide (VT) in patients with BRCA1/2-mutated breast cancer.Patients and methods: Eligible patients ≥18 years with locally recurrent or metastatic breast cancer and a deleterious BRCA1/2 germline mutation were randomized 1 : 1 : 1 to VCP, VT, or placebo plus carboplatin/paclitaxel (PCP). Primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and overall response rate (ORR).Results: Of 290 randomized patients, 284 were BRCA+, confirmed by central laboratory. For VCP versus PCP, median PFS was 14.1 and 12.3 months, respectively [hazard ratio (HR) 0.789; 95% CI 0.536-1.162; P = 0.227], interim median OS 28.3 and 25.9 months (HR 0.750; 95% CI 0.503-1.117; P = 0.156), and ORR 77.8% and 61.3% (P = 0.027). For VT (versus PCP), median PFS was 7.4 months (HR 1.858; 95% CI 1.278-2.702; P = 0.001), interim median OS 19.1 months (HR 1.483; 95% CI 1.032-2.131; P = 0.032), and ORR 28.6% (P Conclusion: Numerical but not statistically significant increases in both PFS and OS were observed in patients with BRCA1/2-mutated recurrent/metastatic breast cancer receiving VCP compared with PCP. The addition of veliparib to carboplatin/paclitaxel significantly improved ORR. There was no clinically meaningful increase in toxicity with VCP versus PCP. VT was inferior to PCP. An ongoing phase III trial is evaluating VCP versus PCP, with optional continuation single-agent therapy with veliparib/placebo if chemotherapy is discontinued without progression, in this patient population.Clinical trial information: NCT01506609. |
| تدمد: | 0150-6609 0923-7534 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e6245faf8fe340df6bb665b1a1db5b1a https://pure.eur.nl/en/publications/f335467b-a340-4640-9706-dda834d92443 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e6245faf8fe340df6bb665b1a1db5b1a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01506609 09237534 |
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