Randomized Phase II Trial of Sapanisertib ± TAK-117 vs. Everolimus in Patients With Advanced Renal Cell Carcinoma After VEGF-Targeted Therapy.

Autor:	Choueiri TK; Dana-Farber Cancer Institute, Boston, MA, USA., Porta C; University of Pavia and IRCCS San Matteo University Hospital Foundation, Pavia, Italy., Suárez C; Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d´Hebron, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain., Hainsworth J; Sarah Cannon Research Institute, Nashville, TN, USA., Voog E; Centre Jean Bernard/Clinique Victor Hugo, Institut Inter-régional de Cancérologie, Le Mans, France., Duran I; Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Cantabria, Spain., Reeves J; Florida Cancer Specialists/Sarah Cannon Research Institute, Fort Myers, FL, USA., Czaykowski P; CancerCare Manitoba, Winnipeg, Manitoba, Canada., Castellano D; i+12 Research Institute, Hospital Universitario 12 de Octubre, Madrid, Spain., Chen J; Takeda Development Center Americas, Inc., Lexington, MA, USA., Sedarati F; Takeda Development Center Americas, Inc., Lexington, MA, USA., Powles T; Barts Cancer Institute, Royal Free NHS Trust, St. Bartholomew's Hospital, London, UK.
Jazyk:	angličtina
Zdroj:	The oncologist [Oncologist] 2022 Dec 09; Vol. 27 (12), pp. 1048-1057.
DOI:	10.1093/oncolo/oyac192
Abstrakt:	Background: Sapanisertib, a dual mTORC1/2 inhibitor, may offer more complete inhibition of the PI3K/AKT/mTOR pathway than mTORC1 inhibitors, such as everolimus. This phase II study evaluated the efficacy and safety of single-agent sapanisertib and sapanisertib plus the PI3Kα inhibitor TAK-117, vs. everolimus in patients with advanced clear cell renal cell carcinoma (ccRCC) that had progressed on or after VEGF-targeted therapy. Materials and Methods: Patients with histologically confirmed, advanced ccRCC were randomized 1:1:1 to receive single-agent everolimus 10 mg once daily, single-agent sapanisertib 30 mg once weekly, or sapanisertib 4 mg plus TAK-117 200 mg, both once daily for 3 days/week, in 28-day cycles. The primary endpoint was progression-free survival (PFS). Results: Ninety-five patients were treated with everolimus or sapanisertib (n = 32 each), or sapanisertib plus TAK-117 (n = 31). There were no significant differences in PFS among the 3 groups or across any subgroups. Median PFS was 3.8 months with everolimus vs. 3.6 months with sapanisertib (HR, 1.33; 95% CI, 0.75-2.36), and 3.1 months with sapanisertib plus TAK-117 (HR, 1.37; 95% CI, 0.75-2.52). No significant differences in overall survival were seen among groups. Overall response rate was 16.7%, 0%, and 7.1%, respectively. Discontinuations due to treatment-emergent adverse events were 15.6%, 28.1%, and 29.0%. Conclusion: Sapanisertib with or without TAK-117 was less tolerable and did not improve efficacy vs. everolimus in patients with advanced ccRCC who had relapsed after or were refractory to VEGF-targeted therapies. Dual mTORC1/2 inhibition may not be an effective therapeutic approach for these patients. (© The Author(s) 2022. Published by Oxford University Press.)
Databáze:	MEDLINE
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