|
|||||
|
|
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 |
|
| Authors: | 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 |
| Affiliation: | 1.Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore ;2.Duke-NUS Medical School, 11 Hospital Crescent, Singapore, Singapore ;3.Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain ;4.Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA ;5.Department of Internal Medicine, Seoul National University Hospital, and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea ;6.Department of Medical Oncology, Breast Disease Center, Hospital Saint Louis, Paris, France ;7.Oncology Division, Northwest Medical Specialties, Puyallup, WA, USA ;8.Department of Solid Tumor and Investigational Therapeutics, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA ;9.Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA ;10.Biostatistics, Genentech, Inc., South San Francisco, CA, USA ;11.Pharma Development, Roche Products Ltd, Welwyn Garden City, UK ;12.Product Development Oncology, Genentech, Inc., South San Francisco, CA, USA ;13.Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea ; |
| Abstract: | 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. MethodsEligible 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. ResultsMedian 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. ConclusionsFinal 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. |
| Keywords: | |
| 本文献已被 SpringerLink 等数据库收录！ | |