A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma

• Published in: Investigational new drugs 2015-02, Vol.33 (1), p.241-246
• Main Authors: Knox, Jennifer J., Qin, Rui, Strosberg, Jonathan R., Tan, Benjamin, Kaubisch, Andreas, El-Khoueiry, Anthony B., Bekaii-Saab, Tanios S., Rousey, Steven R., Chen, Helen X., Erlichman, Charles
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Clinical trials; Disease-Free Survival; Drug development; Drug dosages; Female; Humans; Kinases; Liver cancer; Liver Neoplasms - drug therapy; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Oncology; Patients; Pharmaceutical sciences; Pharmacology/Toxicology; Phase II Studies; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Sirolimus - administration & dosage; Sirolimus - adverse effects; Sirolimus - analogs & derivatives; Studies; Treatment Outcome; Vascular endothelial growth factor
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-014-0169-3

Summary Background There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. Methods A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. Results Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1–18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. Conclusion This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule.