Vascular endothelial growth factor (VEGF) targeting represents the standard first-line therapy for metastatic renal-cell carcinoma (mRCC), while blocking the mammalian target of rapamycin (mTOR) is effective in relapsed disease. Since continuing blockade of VEGF may be of value, we studied the combination of bevacizumab with temsirolimus in mRCC patients relapsing after first-line treatment.
A prospective, phase II study of the combination of bevacizumab (10 mg/kg, every 2 weeks) with temsirolimus (25 mg weekly) in patients with mRCC who failed first-line anti-VEGF treatment. 6-month progression-free survival (PFS) rate was the primary end point. The association of VEGFa, VEGFR2, fibroblast growth factor (FGF) b, platelet-derived growth factor receptor (PDGFR) a and PDGFRb with prognostic factors and outcomes were also studied.
39 patients were enrolled. First-line therapy included: sunitinib (n = 16), bevacizumab/interferon (n = 12), pazopanib (n = 10), sorafenib (n = 1). After a median follow-up of 37 months, 6-month PFS rate was 50.9% [95% confidence interval (CI) 33.8-65.7], median time to progression 6.8 months (95% CI 5.5-9.2) and median overall survival (OS) 18.2 months (95% CI 12.9-27.2). Objective response rate was 27%. The most common AEs were metabolic (33%), renal (8%) and gastrointestinal (GI) (7%). The most common grade 3-5 AEs were GI (18%), infections (14%) and metabolic (25%). Toxicity was the most frequent cause of treatment discontinuation (40%). FGFb levels were associated with OS.
In concert with recent data, our study confirms the efficacy of anti-VEGF/anti-mTOR combination in mRCC relapsing after anti-VEGF therapy. Toxicity was considerable leading to high rate of treatment discontinuations.
International journal of clinical oncology. 2018 Oct 29 [Epub ahead of print]
Aristotelis Bamias, Vasilios Karavasilis, Nikolaos Gavalas, Kimon Tzannis, Epaminontas Samantas, Gerasimos Aravantinos, Angelos Koutras, Ioannis Gkerzelis, Euthymios Kostouros, Konstantinos Koutsoukos, Flora Zagouri, George Fountzilas, Meletios-Athanasios Dimopoulos
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, 80 Vas. Sofias Ave, 115 28, Athens, Greece. ., Department of Medical Oncology, Papageorgiou Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloníki, Greece., Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, 80 Vas. Sofias Ave, 115 28, Athens, Greece. ., Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, 80 Vas. Sofias Ave, 115 28, Athens, Greece., Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece., Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece., Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece., Department of Urology, General Hospital Konstantopouleio Agia Olga, Athens, Greece., Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloníki, Greece.