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29.10.2018 | Original Article

The combination of bevacizumab/temsirolimus after first-line anti-VEGF therapy in advanced renal-cell carcinoma: a clinical and biomarker study

Zeitschrift:
International Journal of Clinical Oncology
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10147-018-1361-9) contains supplementary material, which is available to authorized users.

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Trial registration

ClinicalTrials.gov: NCT01264341

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