A phase Ib, open-label, dose-escalation study of the safety and pharmacology of taselisib (GDC-0032) in combination with either docetaxel or paclitaxel in patients with HER2-negative, locally advanced, or metastatic breast cancer
| Autor: | Andrés Cervantes, Hans Wildiers, Michael C. Wei, Mafalda Oliveira, Carlos Becerra, Cristina Saura, John Bond, Heather M. Moore, Stephen Lane Richey, Todd M. Bauer, Ian E. Krop, Timothy R. Wilson, Philippe L. Bedard, Manish R. Patel, Vandana G Abramson, Na Cui, Eric Reyner |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research Lung Neoplasms Receptor ErbB-2 Docetaxel PI3K chemistry.chemical_compound 0302 clinical medicine Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols Neoplasm Metastasis Aged 80 and over Taselisib Imidazoles Middle Aged Metastatic breast cancer Treatment Outcome Paclitaxel 030220 oncology & carcinogenesis Female medicine.drug Adult medicine.medical_specialty Maximum Tolerated Dose Class I Phosphatidylinositol 3-Kinases Breast Neoplasms PI3K inhibitor 03 medical and health sciences Breast cancer Pharmacokinetics Internal medicine medicine Humans Adverse effect Aged Taxane business.industry Capsule PIK3CA medicine.disease Survival Analysis Oxazepines 030104 developmental biology chemistry Mutation business GDC-0032 |
| ISSN: | 0186-2081 |
| Popis: | PURPOSE: This open-label, phase Ib, dose-escalation, and dose-expansion study (NCT01862081) evaluated taselisib with a taxane in locally advanced or metastatic breast cancer (BC) and/or non-small cell lung cancer (NSCLC). METHODS: Patients received taselisib (2-6 mg tablet or 3-6 mg capsule) plus docetaxel or paclitaxel. Primary endpoints were safety, dose-limiting toxicities, maximum tolerated dose, and identification of a recommended phase II dose. Secondary endpoints included pharmacokinetics and antitumor activity assessment. RESULTS: Eighty patients (BC: 72; NSCLC: 7; BC/NSCLC: 1) were enrolled (docetaxel-receiving arms: 21; paclitaxel-receiving arms: 59). Grade ≥ 3 adverse events (AEs), serious AEs, and AEs leading to death were reported in 90.5%, 42.9%, and 14.3% of patients, respectively (docetaxel-receiving arms), and 78.9%, 40.4%, and 3.5% of patients, respectively (paclitaxel-receiving arms). Eight patients experienced dose-limiting toxicities. The maximum tolerated dose was exceeded with 3 mg taselisib (capsule) for 21 consecutive days plus 75 mg/m2 docetaxel and not exceeded with 6 mg taselisib (tablet) for 5 days on/2 days off plus 80 mg/m2 paclitaxel. Objective response rates and clinical benefit rates were 35.0% and 45.0%, respectively (docetaxel-receiving arms), and 20.4% and 27.8%, respectively (paclitaxel-receiving arms). Exposure for paclitaxel or docetaxel plus taselisib was consistent with the single agents. CONCLUSIONS: Taselisib in combination with a taxane has a challenging safety profile. Despite evidence of antitumor activity, the benefit-risk profile was deemed not advantageous. Further development is not planned. ispartof: BREAST CANCER RESEARCH AND TREATMENT vol:178 issue:1 pages:121-133 ispartof: location:Netherlands status: published |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|