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oai:recercat.cat:11351/105602024-06-06T08:42:12Zcom_2072_378070com_2072_378040col_2072_378092

A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer Han, Sileny Oza, Amit Colombo, Nicoletta Raspagliesi, Francesco Wenham, Robert M. OAKNIN, ANA Institut Català de la Salut [Han SN] Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Department of Oncology, KU Leuven, Gynaecological Oncology, University Hospitals Leuven, Leuven, Belgium. [Oza A] Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [Colombo N] Obstetrics and Gynaecology, University of Milano-Bicocca and European Institute of Oncology IRCCS, Milan, Italy. [Oaknin A] Gynaecologic Cancer Programme, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Raspagliesi F] Gynecological Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. [Wenham RM] Department of Gynecologic Oncology, Moffitt Cancer Center, Tampa, FL, USA Vall d'Hebron Barcelona Hospital Campus Endometri - Càncer - Tractament Quimioteràpia combinada Medicaments antineoplàstics - Ús terapèutic DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Endometrial Neoplasms ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas::neoplasias endometriales TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada Endometrial cancer; Metastatic; Recurrent Càncer d'endometri; Metastàtic; Recurrent Cáncer endometrial; Metastásico; Recurrente Objective This phase 2 study investigated sapanisertib (selective dual inhibitor of mTORC1/2) alone, or in combination with paclitaxel or TAK-117 (a selective small molecule inhibitor of PI3K), versus paclitaxel alone in advanced, recurrent, or persistent endometrial cancer. Methods Patients with histologic diagnosis of endometrial cancer (1–2 prior regimens) were randomized to 28-day cycles on four treatment arms: 1) weekly paclitaxel 80 mg/m2 (days 1, 8, and 15); 2) weekly paclitaxel 80 mg/m2 + oral sapanisertib 4 mg on days 2–4, 9–11, 16–18, and 23–25; 3) weekly sapanisertib 30 mg, or 4) sapanisertib 4 mg + TAK-117 200 mg on days 1–3, 8–10, 15–17, and 22–24. Results Of 241 patients randomized, 234 received treatment (paclitaxel, n = 87 [3 ongoing]; paclitaxel+sapanisertib, n = 86 [3 ongoing]; sapanisertib, n = 41; sapanisertib+TAK-117, n = 20). The sapanisertib and sapanisertib+TAK-117 arms were closed to enrollment after futility analyses. After a median follow-up of 14.4 (paclitaxel) versus 17.2 (paclitaxel+sapanisertib) months, median progression-free survival (PFS; primary endpoint) was 3.7 versus 5.6 months (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.58–1.15; p = 0.139); in patients with endometrioid histology (n = 116), median PFS was 3.3 versus 5.7 months (HR 0.66; 95% CI 0.43–1.03). Grade ≥ 3 treatment-emergent adverse event rates were 54.0% with paclitaxel versus 89.5% paclitaxel+sapanisertib. Conclusions Our findings support inclusion of chemotherapy combinations with investigational agents for advanced or metastatic disease. The primary endpoint was not met and toxicity was manageable. Trial registration: ClinicalTrials.gov number, NCT02725268 Takeda Development Center Americas, Inc., Lexington, MA, USA. This work was supported by funding from Takeda Development Center Americas, Inc. The study was designed by the authors in conjunction with the sponsors. Data were gathered and analyzed by the investigator and the sponsor; all the authors had access to the data. The authors received medical writing support for drafting the manuscript, which was funded by Takeda Pharmaceuticals USA, Inc. Manuscript drafts were reviewed by all authors and the sponsor and all the authors made the decision to submit the manuscript for publication. 2023-11-08T09:50:06Z 2023-11-08T09:50:06Z 2023-11 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Han SN, Oza A, Colombo N, Oaknin A, Raspagliesi F, Wenham RM, et al. A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer. Gynecol Oncol. 2023 Nov;178:110–8. 0090-8258 https://hdl.handle.net/11351/10560 10.1016/j.ygyno.2023.09.013 37839313 http://hdl.handle.net/11351/10560 eng Gynecologic Oncology;178 https://doi.org/10.1016/j.ygyno.2023.09.013 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf Elsevier Scientia