{"doi":"10.1093/oncolo/oyaf413","title":"Phase I study of bevacizumab and temsirolimus combination therapy in advanced malignancies: safety, efficacy, and ovarian cancer expansion","abstract":"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 31.3% ≥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).","journal":"The Oncologist","year":2025,"id":585158,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9231,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01552434"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":290153,"name":"Chieh Tseng","orcid":null,"position":1,"is_corresponding":false},{"id":1498550,"name":"Emily Thompson","orcid":"0009-0009-6178-1393","position":2,"is_corresponding":false},{"id":527267,"name":"R. Jason Stafford","orcid":"0000-0003-4091-8417","position":3,"is_corresponding":false},{"id":426154,"name":"Hung Le","orcid":"0009-0007-8886-926X","position":4,"is_corresponding":false},{"id":346007,"name":"Lei Kang","orcid":"0000-0001-8729-4547","position":5,"is_corresponding":false},{"id":241553,"name":"Siqing Fu","orcid":"0000-0002-1933-0419","position":6,"is_corresponding":false},{"id":108756,"name":"Apostolia M. Tsimberidou","orcid":"0000-0003-2713-233X","position":7,"is_corresponding":false},{"id":1558,"name":"George R. Blumenschein","orcid":"0000-0002-9606-8194","position":8,"is_corresponding":false},{"id":269051,"name":"Jordi Rodon Ahnert","orcid":null,"position":9,"is_corresponding":false},{"id":820513,"name":"John M. Slopis","orcid":"0000-0002-1847-0583","position":10,"is_corresponding":false},{"id":107725,"name":"David S. Hong","orcid":"0000-0001-8721-1609","position":11,"is_corresponding":false},{"id":266105,"name":"Aung Naing","orcid":"0000-0002-4803-8513","position":12,"is_corresponding":false},{"id":70220,"name":"Funda Meric‐Bernstam","orcid":"0000-0001-6816-6072","position":13,"is_corresponding":false},{"id":661415,"name":"Chaan S. Ng","orcid":"0000-0001-9261-7021","position":14,"is_corresponding":false},{"id":233757,"name":"Shannon N. Westin","orcid":"0000-0002-1922-0156","position":15,"is_corresponding":false},{"id":274989,"name":"Anil K. Sood","orcid":"0000-0003-4242-1762","position":16,"is_corresponding":false},{"id":258839,"name":"Sarina A. Piha‐Paul","orcid":"0000-0001-9455-1660","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T02:59:20.067334Z","pmid":"41389341","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}