Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial
| Autor: | J.Y. Hsu, Na Cui, Susan Dent, Sofia Sousa, Timothy R. Wilson, Véronique Diéras, William Jacot, Ian E. Krop, Frauke Schimmoller, M. De Laurentiis, Nadia Harbeck, Yunjoo Im, Jing He, J. Cortes, Pamela Drullinsky |
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| Přispěvatelé: | Dent, S., Cortes, J., Im, Y. -H., Dieras, V., Harbeck, N., Krop, I. E., Wilson, T. R., Cui, N., Schimmoller, F., Hsu, J. Y., He, J., De Laurentiis, M., Sousa, S., Drullinsky, P., Jacot, W. |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Receptor ErbB-2 PIK3CA mutation Gastroenterology law.invention Phosphatidylinositol 3-Kinases 0302 clinical medicine Randomized controlled trial law Antineoplastic Combined Chemotherapy Protocols Clinical endpoint Fulvestrant Class I Phosphatidylinositol 3-Kinase advanced breast cancer education.field_of_study Hazard ratio Imidazoles Hematology Receptors Estrogen Oncology 030220 oncology & carcinogenesis Female Breast Neoplasm Human medicine.drug medicine.medical_specialty Class I Phosphatidylinositol 3-Kinases medicine.drug_class Population Breast Neoplasms PI3K inhibitor Placebo 03 medical and health sciences Internal medicine taselisib medicine Humans education Adverse effect Imidazole Antineoplastic Combined Chemotherapy Protocol Aromatase inhibitor Oxazepine business.industry Oxazepines 030104 developmental biology Quality of Life Phosphatidylinositol 3-Kinase Neoplasm Recurrence Local business |
| Zdroj: | Annals of Oncology. 32:197-207 |
| ISSN: | 0923-7534 |
| DOI: | 10.1016/j.annonc.2020.10.596 |
| Popis: | Background The phase III SANDPIPER study assessed taselisib (GDC-0032), a potent, selective PI3K inhibitor, plus fulvestrant in estrogen receptor-positive, HER2-negative, PIK3CA-mutant locally advanced or metastatic breast cancer. Patients and methods Postmenopausal women with disease recurrence/progression during/after an aromatase inhibitor were randomized 2 : 1 to receive taselisib (4 mg; taselisib arm) or placebo (placebo arm) plus fulvestrant (500 mg). Stratification factors were visceral disease, endocrine sensitivity, and geographic region. Patients with PIK3CA-mutant tumors (central cobas® PIK3CA Mutation Test) were randomized separately from those without detectable mutations. The primary endpoint was investigator-assessed progression-free survival (INV-PFS) in patients with PIK3CA-mutant tumors. Secondary endpoints included objective response rate, overall survival, clinical benefit rate, duration of objective response, PFS by blinded independent central review (BICR-PFS), safety, and time to deterioration in health-related quality of life. Results The PIK3CA-mutant intention-to-treat population comprised 516 patients (placebo arm: n = 176; taselisib arm: n = 340). INV-PFS was significantly improved in the taselisib {7.4 months [95% confidence interval (CI), 7.26-9.07]} versus placebo arm (5.4 months [95% CI, 3.68-7.29]) (stratified hazard ratio [HR] 0.70; 95% CI, 0.56-0.89; P = 0.0037) and confirmed by BICR-PFS (HR 0.66). Secondary endpoints, including objective response rate, clinical benefit rate, and duration of objective response, showed consistent improvements in the taselisib arm. Safety was assessed in all randomized patients who received at least one dose of taselisib/placebo or fulvestrant regardless of PIK3CA-mutation status (n = 629). Serious adverse events were lower in the placebo versus taselisib arm (8.9% versus 32.0%). There were more discontinuations (placebo arm: 2.3%; taselisib arm: 16.8%) and dose reductions (placebo arm: 2.3%; taselisib arm: 36.5%) in the taselisib arm. Conclusion SANDPIPER met its primary endpoint; however, the combination of taselisib plus fulvestrant has no clinical utility given its safety profile and modest clinical benefit. |
| Databáze: | OpenAIRE |
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