Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study
| Autor: | Stuart J. Turner, Stephen Chia, Nicholas C. Turner, Wei-Chun Hsu, Yeon Hee Park, Patrick Neven, Florence Lerebours, Pamela Drullinsky, Christina Arce, Manuel Ruiz-Borrego, Yu-Ming Shen, Eva Ciruelos, Juan Pablo Zarate, Hope S. Rugo, Nickolas Sophos, Dejan Juric, Aleix Prat, Thomas Bachelot, Hemanth Kanakamedala |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
0301 basic medicine Oncology medicine.medical_specialty Adolescent Class I Phosphatidylinositol 3-Kinases Receptor ErbB-2 medicine.drug_class Breast Neoplasms 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Clinical endpoint Humans Fulvestrant Aged Aromatase inhibitor Aromatase Inhibitors business.industry Cyclin-Dependent Kinase 4 Cancer Cyclin-Dependent Kinase 6 Middle Aged medicine.disease Chemotherapy regimen Rash Thiazoles 030104 developmental biology Receptors Estrogen Response Evaluation Criteria in Solid Tumors 030220 oncology & carcinogenesis Cohort Female Estrogen Receptor Antagonists medicine.symptom Receptors Progesterone business medicine.drug |
| Zdroj: | The Lancet Oncology. 22:489-498 |
| ISSN: | 1470-2045 |
| DOI: | 10.1016/s1470-2045(21)00034-6 |
| Popis: | Summary Background Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A. Methods This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide. Participants aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 2 or less, with no more than two previous anticancer treatments and no more than one previous chemotherapy regimen, were enrolled in three cohorts. In cohort A, patients must have had progression on or after a CDK4/6 inhibitor plus an aromatase inhibitor as the immediate previous treatment. Patients received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary endpoint was the proportion of patients alive without disease progression at 6 months per local assessment using Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation. This trial is registered with ClinicalTrials.gov , NCT03056755 . Findings Between Aug 14, 2017, and Dec 17, 2019 (data cutoff), 127 patients with at least 6 months' follow-up were enrolled into cohort A. 121 patients had a centrally confirmed PIK3CA mutation. At data cutoff, median follow-up was 11·7 months (IQR 8·5–15·9). 61 (50·4%; 95% CI 41·2–59·6) of 121 patients were alive without disease progression at 6 months. The most frequent grade 3 or worse adverse events were hyperglycaemia (36 [28%] of 127 patients), rash (12 [9%]), and rash maculopapular (12 [9%]). Serious adverse events occurred in 33 (26%) of 127 patients. No treatment-related deaths were reported. Interpretation BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor. Funding Novartis Pharmaceuticals. |
| Databáze: | OpenAIRE |
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