Academic Journal
Assessing the Safety and Efficacy of Two Starting Doses of Lenvatinib Plus Everolimus in Patients with Renal Cell Carcinoma: A Randomized Phase 2 Trial
| العنوان: | Assessing the Safety and Efficacy of Two Starting Doses of Lenvatinib Plus Everolimus in Patients with Renal Cell Carcinoma: A Randomized Phase 2 Trial |
|---|---|
| المؤلفون: | Pal, Samantha K, Puente, Javier, Heng, DYC, Glen, H, Koralewski, P, Stroyakovskiy, D, Alekseev, B, Parnis, F, Castellano, D, Ciuleanu, T, Lee, JL, Sunela, K, O'Hara, K, Binder, TA, Peng, L, Smith, AD, Rha, SY |
| المصدر: | Eur Urol, 82(3), 283-292, (2024-08-01) |
| بيانات النشر: | Zenodo |
| سنة النشر: | 2024 |
| المجموعة: | Zenodo |
| مصطلحات موضوعية: | Antineoplastic combined chemotherapy protocols, Carcinoma, Renal Cell, Everolimus, Humans, Kidney Neoplasms, Phenylurea Compounds, Quinolines, Vascular Endothelial Growth Factor A |
| الوصف: | Background: Lenvatinib (18 mg) plus everolimus (5 mg) is approved for patients with advanced renal cell carcinoma (RCC) after one or more prior antiangiogenic therapies. Objective: To assess whether a lower starting dose of lenvatinib has comparable efficacy with improved tolerability for patients with advanced RCC treated with lenvatinib plus everolimus. Design, setting, and participants: A randomized, open-label, phase 2 global trial was conducted in patients with advanced clear cell RCC and disease progression after one prior vascular endothelial growth factor-targeted therapy (prior anti-programmed death-1/programmed death ligand-1 therapy permitted). Intervention: Patients were randomly assigned 1:1 to the 14- or 18-mg lenvatinib starting dose, both in combination with everolimus 5 mg/d. Patients in the 14-mg arm were to be uptitrated to lenvatinib 18 mg at cycle 2, day 1, barring intolerable grade 2 or any grade ≥3 treatment-emergent adverse events (TEAEs) requiring dose reduction occurring in the first 28-d cycle. Outcome measurements and statistical analysis: The primary efficacy endpoint was investigator-assessed objective response rate (ORR) as of week 24 (ORR wk24 ); the noninferiority threshold of the 14- versus 18-mg arm was p ≤ 0.045. The primary safety endpoint was the proportion of patients with intolerable grade 2 or any grade ≥3 TEAEs within 24 wk of randomization. Results and limitations: The ORR wk24 for the 14-mg arm (32% [95% confidence interval {CI} 25-39]) was not noninferior to the ORR wk24 in the 18-mg arm (35% [95% CI 27-42]; odds ratio: 0.88; 90% CI 0.59-1.32; p = 0.3). The proportion of intolerable grade 2 or any grade ≥3 TEAEs was similar between the two arms (14 mg, 83% vs 18 mg, 80%; p = 0.5). The secondary endpoints of overall ORR, progression-free survival, and overall survival numerically favored the 18-mg arm. A limitation of this study was that the study design did not allow for a full comparison of progression-free survival between treatment arms. Conclusions: The study ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://doi.org/10.1016/j.eururo.2021.12.024; oai:zenodo.org:13152236 |
| DOI: | 10.1016/j.eururo.2021.12.024 |
| الاتاحة: | https://doi.org/10.1016/j.eururo.2021.12.024 |
| Rights: | info:eu-repo/semantics/restrictedAccess ; Creative Commons Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/legalcode |
| رقم الانضمام: | edsbas.C4B230F |
| قاعدة البيانات: | BASE |
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