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Final results of the double-blind placebo-controlled randomized phase 2 LOTUS trial of first-line ipatasertib plus paclitaxel for inoperable locally advanced/metastatic triple-negative breast cancer.
Dent, Rebecca; Oliveira, Mafalda; Isakoff, Steven J; Im, Seock-Ah; Espié, Marc; Blau, Sibel; Tan, Antoinette R; Saura, Cristina; Wongchenko, Matthew J; Xu, Na; Bradley, Denise; Reilly, Sarah-Jayne; Mani, Aruna; Kim, Sung-Bae.
Afiliación
  • Dent R; Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore. rebecca.dent@duke-nus.edu.sg.
  • Oliveira M; Duke-NUS Medical School, 11 Hospital Crescent, Singapore, Singapore. rebecca.dent@duke-nus.edu.sg.
  • Isakoff SJ; Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • Im SA; Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA.
  • Espié M; Department of Internal Medicine, Seoul National University Hospital, and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • Blau S; Department of Medical Oncology, Breast Disease Center, Hospital Saint Louis, Paris, France.
  • Tan AR; Oncology Division, Northwest Medical Specialties, Puyallup, WA, USA.
  • Saura C; Department of Solid Tumor and Investigational Therapeutics, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
  • Wongchenko MJ; Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • Xu N; Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA.
  • Bradley D; Biostatistics, Genentech, Inc., South San Francisco, CA, USA.
  • Reilly SJ; Pharma Development, Roche Products Ltd, Welwyn Garden City, UK.
  • Mani A; Pharma Development, Roche Products Ltd, Welwyn Garden City, UK.
  • Kim SB; Product Development Oncology, Genentech, Inc., South San Francisco, CA, USA.
Breast Cancer Res Treat ; 189(2): 377-386, 2021 Sep.
Article en En | MEDLINE | ID: mdl-34264439
PURPOSE: In LOTUS (NCT02162719), adding the oral AKT inhibitor ipatasertib to first-line paclitaxel for locally advanced/metastatic triple-negative breast cancer (aTNBC) improved progression-free survival (PFS; primary endpoint), with an enhanced effect in patients with PIK3CA/AKT1/PTEN-altered tumors (FoundationOne next-generation sequencing [NGS] assay). We report final overall survival (OS) results. METHODS: Eligible patients had measurable previously untreated aTNBC. Patients were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status, and were randomized 1:1 to paclitaxel 80 mg/m2 (days 1, 8, 15) plus ipatasertib 400 mg or placebo (days 1-21) every 28 days until disease progression or unacceptable toxicity. OS (intent-to-treat [ITT], immunohistochemistry PTEN-low, and PI3K/AKT pathway-activated [NGS PIK3CA/AKT1/PTEN-altered] populations) was a secondary endpoint. RESULTS: Median follow-up was 19.0 versus 16.0 months in the ipatasertib-paclitaxel versus placebo-paclitaxel arms, respectively. In the ITT population (n = 124), median OS was numerically longer with ipatasertib-paclitaxel than placebo-paclitaxel (hazard ratio 0.80, 95% CI 0.50-1.28; median 25.8 vs 16.9 months, respectively; 1-year OS 83% vs 68%). Likewise, median OS favored ipatasertib-paclitaxel in the PTEN-low (n = 48; 23.1 vs 15.8 months; hazard ratio 0.83) and PIK3CA/AKT1/PTEN-altered (n = 42; 25.8 vs 22.1 months; hazard ratio 1.13) subgroups. The ipatasertib-paclitaxel safety profile was unchanged. CONCLUSIONS: Final OS results show a numerical trend favoring ipatasertib-paclitaxel and median OS exceeding 2 years with ipatasertib-paclitaxel. Overall, results are consistent with the reported PFS benefit; interpretation within biomarker-defined subgroups is complicated by small sample sizes and TNBC heterogeneity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Neoplasias de la Mama Triple Negativas Tipo de estudio: Clinical_trials Límite: Female / Humans Idioma: En Revista: Breast Cancer Res Treat Año: 2021 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Neoplasias de la Mama Triple Negativas Tipo de estudio: Clinical_trials Límite: Female / Humans Idioma: En Revista: Breast Cancer Res Treat Año: 2021 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Países Bajos