Phase I Study of Bevacizumab and Temsirolimus Combination Therapy in Advanced Malignancies: Safety, Efficacy, and Ovarian Cancer Expansion
Mené sur 48 patients ayant reçu plusieurs lignes thérapeutiques pour une tumeur solide de stade avancé (âge médian : 59 ans ; 27% de cas de tumeur ovarienne ; nombre médian de thérapies antérieures : 4), cet essai de phase I détermine la dose maximale tolérée du bévacizumab en combinaison avec le temsirolimus puis évalue l'efficacité de cette combinaison du point de vue du taux de réponse objective
Background: Bevacizumab and temsirolimus target angiogenic and mTOR pathways in cancer progression.
Methods: This phase I study enrolled 48 heavily pretreated patients with advanced solid tumors, including an ovarian cancer expansion cohort. Patients received bevacizumab biweekly plus temsirolimus weekly in a 3 + 3 design to assess safety, maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Exploratory analyses included tumor genomic profiling and dynamic contrast-enhanced MRI (DCE-MRI).
Results: Patients had a median age of 59 and median four prior therapies. Common tumor types were ovarian (27%) and head and neck (15%). Treatment-related adverse events occurred in 93.8%, with 31.2% ≥grade 3. Five patients experienced DLTs, including grade 3 enteritis, fatigue, bowel obstruction/abdominal ileus/pulmonary embolism, bowel perforation and grade 3/4 elevated liver enzymes. MTD was bevacizumab 10 mg/kg biweekly plus temsirolimus 20 mg weekly. Overall, objective response rate (ORR) was 7.3% and 19.5% achieved stable disease ≥6 months (clinical benefit rate [CBR] 26.8%). In ovarian cohort, ORR was 16.7% and CBR 33.3%. Patients with tumor regression on DCE-MRI had lower
ΔKtrans values.
Conclusion
:
Combination therapy showed acceptable safety and modest activity. Molecular and imaging findings were exploratory and limited. These preliminary observations could inform future biomarker studies. (ClinicalTrials.gov Identifier: NCT01552434)
The Oncologist , résumé, 2025