Pictilisib PI3Kinase inhibitor (a phosphatidylinositol 3-kinase [PI3K] inhibitor) plus paclitaxel for the treatment of hormone receptor-positive, HER2-negative, locally recurrent, or metastatic breast cancer: interim analysis of the multicentre, placebo-controlled, phase II randomised PEGGY study
| Autor: | Stephen Chan, F. Abell, D. Apt, Isabelle Rooney, Rebecca Roylance, Robert W. Laing, J. Zhou, Stina M. Singel, Louis Fehrenbacher, Peter Vuylsteke, Steven Gendreau, Katarína Petráková, Manon T. Huizing |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Adult medicine.medical_specialty Indazoles Paclitaxel Class I Phosphatidylinositol 3-Kinases Receptor ErbB-2 Population Breast Neoplasms Placebo Antibodies Monoclonal Humanized Disease-Free Survival 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols Clinical endpoint medicine Humans Neoplasm Metastasis education Adverse effect Aged education.field_of_study Sulfonamides business.industry Hazard ratio Hematology Middle Aged medicine.disease Interim analysis Metastatic breast cancer Surgery 030104 developmental biology chemistry 030220 oncology & carcinogenesis Female Human medicine Neoplasm Recurrence Local business |
| Zdroj: | Annals of oncology Europe PubMed Central |
| ISSN: | 0923-7534 |
| Popis: | Background Approximately 40% of hormone receptor-positive, HER2-negative breast cancers (BCs) are associated with activating mutations of the phosphatidylinositol 3-kinase (PI3K) pathway. Pictilisib, a potent and highly specific class I pan-PI3K inhibitor, demonstrated preclinical activity in BC cell lines and may potentiate the effect of taxanes, benefiting patients with or without aberrant activation of the PI3K pathway. PEGGY (NCT01740336), a randomised, placebo-controlled phase II trial, examined whether pictilisib augments the anti-tumour activity of paclitaxel in patients with hormone receptor-positive, HER2-negative locally recurrent or metastatic BC (mBC). We report results from the protocol-specified interim analysis. Patients and methods One hundred and eighty-three eligible patients were randomised (1:1) to receive paclitaxel (90 mg/m2 weekly for 3 weeks in every 28-day cycle) with either 260 mg pictilisib or placebo (daily on days 1–5 every week). The primary end point was progression-free survival (PFS) in the intention-to-treat (ITT) population and patients with PIK3CA-mutated tumours. Secondary end points included overall response rate (ORR), duration of response, and safety. Results In the ITT population, the median PFS was 8.2 months with pictilisib (n = 91) versus 7.8 months with placebo (n = 92) [hazard ratio (HR) for progression or death, 0.95; 95% confidence interval (CI) 0.62–1.46; P = 0.83]. In patients with PIK3CA-mutated tumours, the median PFS was 7.3 months for pictilisib (n = 32) versus 5.8 months with placebo (n = 30) (HR, 1.06; 95% CI 0.52–2.12; P = 0.88). ORR was similar between treatment arms. The safety profile of pictilisib was consistent with previous reports, with no new safety signals. Proportions of patients with grade ≥3 adverse events (AEs), serious AEs, and dose reductions/discontinuations due to AEs were higher with pictilisib. Conclusions PEGGY did not meet its primary end point, revealing no significant benefit from adding pictilisib to paclitaxel for patients with hormone receptor-positive, HER2-negative locally recurrent or mBC. Clinical trial number NCT01740336. |
| Databáze: | OpenAIRE |
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