Efficacy and safety of the combination of bevacizumab (BEV) and temsirolimus (TEM) in patients with metastatic renal cancer (mRCC) after first-line anti-VEGF treatment: A Hellenic Cooperative Oncology group (HeCOG) phase II trial

Background

Anti vascular endothelial growth factor (aVEGF) agents represent the standard 1^st-line therapy for mRCC. Monotherapy with agents blocking VEGF, mTOR or PD1/PD-L1 interaction are approved therapies. Since post progression blockade of VEGF may be of value, we studied the combination of BEV+TEM in mRCC patients relapsing after 1^st-line treatment.

Methods

A prospective, phase II, multicenter, trial evaluating the combination of BEV(10mg/kg, every 2 weeks) withTEM(25 mg weekly), until progression of the disease or unacceptable toxicity, was conducted in patients with mRCC who failed first-line aVEGF treatment. No previous therapy for relapsed disease was allowed. % of 6-month progression-free survival (PFS) was the primary end point.

Results

39 patients were enrolled and 37 of them were evaluable for response. 1^st-line therapy included: sunitinib (16), bevacizumab/interferon (12), pazopanib (10), sorafenib (1). The median age was 67 (40-80) years. Clear cell histology was present in 97% of patients, while 69% had PS 0. 51% of patients were progression-free at 6 months (95% CIs: 34-66) and 20% (95% CIs: 9-34) at 12 months. The median time to progression was 6.8 months (95%CI 5.5-9.2) and the overall survival 18.2 months (95%CI 12.9-27.2). Best responses were: complete-1 (2.7%), partial-9(24.3%), stable disease-20 (54.1%), progression-7(18.9%). Worst toxicities were of grade: 1 in 1 case (3%), 2 in 20 (51%), 3 in 15 (38%), 4 in 2 (5%), 5 in 1 (3%). The most common adverse evets (AEs) were metabolic (44%), gastrointestinal (11%) and myelotoxicity (9%). The most common grade 3 and 4 AEs were infection (10%), hypertension (5%), hypertriglyceridemia (5%) and mucositis (5%).Toxicity was the most frequent cause of treatment discontinuation (33%).

Conclusions

The combination of BEV and TEMis active in mRCC patients relapsing after a VEGF 1^st-line treatment. Our study confirms recent encouraging data of another anti-VEGF/anti-mTOR combination in this population. Nevertheless, toxicity was considerable leading to the discontinuation of therapy in 1/3 of patients.

Clinical trial identification

NCT01264341

EudraCT: 2010-020664-38

Legal entity responsible for the study

Hellenic Cooperative Oncology Group

Funding

Pfizer

Disclosure

K. Koutsoukos: Honoraria from Novartis. F. Zagouri: Honoraria from Novartis, Roche. E. Kostouros: Honoraria Janssen. M. Liontos: Janssen Honoraria. M. Dimopoulos: Honoraria from Celgene, Janssen, Takeda and Amgen. A. Bamias: Pfizer, Roche, Novartis, Bayer (Honoraria). All other authors have declared no conflicts of interest.