دورية أكاديمية
أعرض في EDS

A phase 1 study of veliparib (ABT-888) plus weekly carboplatin and paclitaxel in advanced solid malignancies, with an expansion cohort in triple negative breast cancer (TNBC) (ETCTN 8620).

التفاصيل البيبلوغرافية
العنوان: A phase 1 study of veliparib (ABT-888) plus weekly carboplatin and paclitaxel in advanced solid malignancies, with an expansion cohort in triple negative breast cancer (TNBC) (ETCTN 8620).
المؤلفون: Malhotra MK; Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Pahuja S; Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Kiesel BF; Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.; Department of Pharmaceutical Sciences, School of Pharmacy, Pittsburgh, PA, USA., Appleman LJ; Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Ding F; Biostatistics Facility, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Lin Y; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.; UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Tawbi HA; Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Stoller RG; Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Lee JJ; Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Belani CP; Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA, USA., Chen AP; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, USA.; Center for Cancer Research, National Cancer Institute, Bethesda, USA., Giranda VL; AbbVie Laboratories, North Chicago, IL, USA., Shepherd SP; AbbVie Laboratories, North Chicago, IL, USA., Emens LA; Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Ivy SP; Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Chu E; Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.; Cancer Therapeutics Program, Montefiore Einstein Cancer Center, Bronx, NY, USA., Beumer JH; Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. beumerj@gmail.com.; Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. beumerj@gmail.com.; Department of Pharmaceutical Sciences, School of Pharmacy, Pittsburgh, PA, USA. beumerj@gmail.com.; UPMC Hillman Cancer Center, Hillman Research Pavilion, Room G27E, 5117 Centre Avenue, Pittsburgh, PA, 15213-1863, USA. beumerj@gmail.com., Puhalla S; Division of Hematology/Oncology, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. puhallasl@upmc.edu.; Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. puhallasl@upmc.edu.; UPMC Magee Women's Hospital, 300 Halket Street, Pittsburgh, PA, 15213, USA. puhallasl@upmc.edu.
المصدر: Breast cancer research and treatment [Breast Cancer Res Treat] 2023 Apr; Vol. 198 (3), pp. 487-498. Date of Electronic Publication: 2023 Feb 28.
نوع المنشور: Clinical Trial, Phase I; Journal Article
اللغة: English
بيانات الدورية: Publisher: Kluwer Academic Country of Publication: Netherlands NLM ID: 8111104 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7217 (Electronic) Linking ISSN: 01676806 NLM ISO Abbreviation: Breast Cancer Res Treat Subsets: MEDLINE
أسماء مطبوعة: Publication: Dordrecht : Kluwer Academic
Original Publication: The Hague ; Boston : M. Nijhoff, c1981-
مواضيع طبية MeSH: Breast Neoplasms*/pathology , Triple Negative Breast Neoplasms*/drug therapy , Triple Negative Breast Neoplasms*/etiology , Anemia*/chemically induced, Humans ; Female ; Carboplatin ; Paclitaxel ; Antineoplastic Combined Chemotherapy Protocols/adverse effects
مستخلص: Background: Veliparib is a poly-ADP-ribose polymerase (PARP) inhibitor, and it has clinical activity with every 3 weeks carboplatin and paclitaxel. In breast cancer, weekly paclitaxel is associated with improved overall survival. We aimed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib with weekly carboplatin and paclitaxel as well as safety, pharmacokinetics, and preliminary clinical activity in triple negative breast cancer (TNBC).
Methods: Patients with locally advanced/metastatic solid tumors and adequate organ function were eligible. A standard 3 + 3 dose-escalation design was followed by a TNBC expansion cohort. Veliparib doses ranging from 50 to 200 mg orally bid were tested with carboplatin (AUC 2) and paclitaxel (80 mg/m 2 ) given weekly in a 21-day cycle. Adverse events (AE) were evaluated by CTCAE v4.0, and objective response rate (ORR) was determined by RECIST 1.1.
Results: Thirty patients were enrolled, of whom 22 had TNBC. Two dose-limiting toxicities were observed. The RP2D was determined to be 150 mg PO bid veliparib with weekly carboplatin and paclitaxel 2 weeks on, 1 week off, based on hematologic toxicity requiring dose reduction in the first 5 cycles of treatment. The most common grade 3/4 AEs included neutropenia, anemia, and thrombocytopenia. PK parameters of veliparib were comparable to single-agent veliparib. In 23 patients with evaluable disease, the ORR was 65%. In 19 patients with TNBC with evaluable disease, the ORR was 63%.
Conclusion: Veliparib can be safely combined with weekly paclitaxel and carboplatin, and this triplet combination has promising clinical activity.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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معلومات مُعتمدة: UL1 TR001857 United States TR NCATS NIH HHS; UM1 CA186690 United States CA NCI NIH HHS; P30 CA047904 United States CA NCI NIH HHS; P30CA047904 United States BC NCI NIH HHS; U01CA099168 United States BC NCI NIH HHS; UM1CA186690 United States BC NCI NIH HHS; U01 CA099168 United States CA NCI NIH HHS; U24CA247643 United States BC NCI NIH HHS; U24 CA247643 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: DNA damage; PARP; Pharmacokinetics; Phase 1 study; Solid tumors; Triple negative breast cancer; Veliparib
المشرفين على المادة: BG3F62OND5 (Carboplatin)
P88XT4IS4D (Paclitaxel)
01O4K0631N (veliparib)
تواريخ الأحداث: Date Created: 20230228 Date Completed: 20230327 Latest Revision: 20240402
رمز التحديث: 20240402
مُعرف محوري في PubMed: PMC10710035
DOI: 10.1007/s10549-023-06889-0
PMID: 36853577
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-7217
DOI:10.1007/s10549-023-06889-0