Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial

Purpose PI3K/AKT pathway alterations are frequent in hormone receptor-positive (HR+) breast cancers. IPATunity130 Cohort B investigated ipatasertib–paclitaxel in PI3K pathway-mutant HR+ unresectable locally advanced/metastatic breast cancer (aBC). Methods Cohort B of the randomized, double-blind, pl...

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Vydáno v:	Breast Cancer Research and Treatment Ročník 191; číslo 3; s. 565 - 576
Hlavní autoři:	Turner, Nicholas, Dent, Rebecca A., O’Shaughnessy, Joyce, Kim, Sung-Bae, Isakoff, Steven J., Barrios, Carlos, Saji, Shigehira, Bondarenko, Igor, Nowecki, Zbigniew, Lian, Qinshu, Reilly, Sarah-Jayne, Hinton, Heather, Wongchenko, Matthew J., Kovic, Bruno, Mani, Aruna, Oliveira, Mafalda
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Springer Science and Business Media LLC 01.02.2022 Springer US Springer Springer Nature B.V
Témata:	1-Phosphatidylinositol 3-kinase AKT protein AKT1 protein Analysis Antineoplastic Combined Chemotherapy Protocols Antineoplastic Combined Chemotherapy Protocols - adverse effects Breast cancer Breast Neoplasms Breast Neoplasms - drug therapy Breast Neoplasms - genetics Cancer research Care and treatment Chemotherapy Class I Phosphatidylinositol 3-Kinases Class I Phosphatidylinositol 3-Kinases - genetics Clinical Trial Clinical trials Diarrhea Double-Blind Method Endocrine therapy ErbB-2 protein Female First-line HER2 negative Hormone receptor positive Hormones Humans Ipatasertib Leukocytes (neutrophilic) Mama - Càncer - Tractament Medicaments antineoplàstics - Efectes secundaris Medicine Medicine & Public Health Metastases NCT NCT03337724 neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] Neoplasm Recurrence, Local Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] Neutropenia Oncology Other subheadings::Other subheadings::/adverse effects [Other subheadings] Other subheadings::Other subheadings::/drug therapy [Other subheadings] Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores] Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] Paclitaxel Paclitaxel - adverse effects Peripheral neuropathy Phosphatidylinositol 3-Kinases PI3K/AKT Piperazines Placebos Proto-Oncogene Proteins c-akt PTEN Phosphohydrolase PTEN Phosphohydrolase - genetics PTEN protein Pyrimidines Receptor, ErbB-2 Receptor, ErbB-2 - genetics terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] Toxicity HER2 negative Ipatasertib First-line Hormone receptor positive PI3K/AKT
ISSN:	0167-6806, 1573-7217, 1573-7217
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Shrnutí:	Purpose PI3K/AKT pathway alterations are frequent in hormone receptor-positive (HR+) breast cancers. IPATunity130 Cohort B investigated ipatasertib–paclitaxel in PI3K pathway-mutant HR+ unresectable locally advanced/metastatic breast cancer (aBC). Methods Cohort B of the randomized, double-blind, placebo-controlled, phase 3 IPATunity130 trial enrolled patients with HR+ HER2-negative PIK3CA / AKT1/PTEN -altered measurable aBC who were considered inappropriate for endocrine-based therapy (demonstrated insensitivity to endocrine therapy or visceral crisis) and were candidates for taxane monotherapy. Patients with prior chemotherapy for aBC or relapse < 1 year since (neo)adjuvant chemotherapy were ineligible. Patients were randomized 2:1 to ipatasertib (400 mg, days 1–21) or placebo, plus paclitaxel (80 mg/m 2 , days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Results Overall, 146 patients were randomized to ipatasertib–paclitaxel and 76 to placebo–paclitaxel. In both arms, median investigator-assessed PFS was 9.3 months (hazard ratio, 1.00, 95% CI 0.71–1.40) and the objective response rate was 47%. Median paclitaxel duration was 6.9 versus 8.8 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively; median ipatasertib/placebo duration was 8.0 versus 9.1 months, respectively. The most common grade ≥ 3 adverse events were diarrhea (12% with ipatasertib–paclitaxel vs 1% with placebo–paclitaxel), neutrophil count decreased (9% vs 7%), neutropenia (8% vs 9%), peripheral neuropathy (7% vs 3%), peripheral sensory neuropathy (3% vs 5%) and hypertension (1% vs 5%). Conclusion Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN -altered HR+ HER2-negative aBC. The ipatasertib–paclitaxel safety profile was consistent with each agent’s known adverse effects. Trial registration NCT03337724.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3
ISSN:	0167-6806 1573-7217 1573-7217
DOI:	10.1007/s10549-021-06450-x