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Overall survival in patients with metastatic renal cell carcinoma initially treated with bevacizumab plus interferon‐α2a and subsequent therapy with tyrosine kinase inhibitors: a retrospective analysis of the phase III AVOREN trial
Author(s) -
Bracarda Sergio,
Bellmunt Joaquim,
Melichar Bohuslav,
Négrier Sylvie,
Bajetta Emilio,
Ravaud Alain,
Sneller Vesna,
Escudier Bernard
Publication year - 2011
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2010.09707.x
Subject(s) - medicine , bevacizumab , renal cell carcinoma , oncology , combination therapy , randomized controlled trial , placebo , surgery , gastroenterology , chemotherapy , pathology , alternative medicine
Study Type – Therapy (RCT)
Level of Evidence 1b What’s known on the subject? and What does the study add? Multiple active treatment options are available for patients with mRCC. Current data suggest that it is difficult to use these therapies in combination due to toxicity concerns. The ability to use these active therapies sequentially provides the potential for improved patient outcomes. This retrospective post‐hoc analysis from a double‐blind, randomized phase III study provides further evidence for improved outcomes with sequential treatment in patients with mRCC. Additionally, it suggests the potential for improved outcomes and long‐term survival (>3 years) with first‐line bevacizumab plus IFN followed by subsequent TKI therapy in patients with mRCC and good/intermediate MSKCC risk at baseline. OBJECTIVE• To retrospectively evaluate the effect of subsequent tyrosine kinase inhibitors (TKIs) after first‐line bevacizumab + interferon‐α2a (IFN) or IFN + placebo in the phase III AVOREN (Avastin and Roferon in Renal Cell Carcinoma) trial.PATIENTS AND METHODS• A total of 649 patients with untreated metastatic renal cell carcinoma (mRCC) were randomized to receive IFN (9 MIU three times a week for up to 1 year) in combination with bevacizumab (10 mg/kg every 2 weeks) or placebo until disease progression. • The protocol allowed the use of any post‐protocol anti‐cancer therapy for patients with progressive disease or those in whom the trial therapy was discontinued. Data regarding the timing and type of subsequent therapy were recorded and overall survival (OS) analysed.RESULTS• Patients were randomized to bevacizumab + IFN ( n = 327) or IFN + placebo ( n = 322); 180 (55%) patients in the bevacizumab + IFN, and 202 (63%) in the IFN + placebo arm, received post‐protocol anti‐cancer therapy. • TKIs were the most common post‐protocol therapy, received by 113 (35%) and 120 (37%) patients in the bevacizumab + IFN and IFN + placebo arms, respectively. • The median OS in patients who received any subsequent TKI was 38.6 months in the bevacizumab + IFN arm and 33.6 months in IFN + placebo arm [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.56–1.13; P = 0.203]. In an additional retrospective analysis that censored patients who received subsequent TKIs, median OS was 25.0 and 20.7 months, respectively, in the bevacizumab + IFN and IFN + placebo arms (HR, 0.84; 95% CI, 0.67–1.05; P = 0.123).CONCLUSIONS• These retrospective exploratory data of sequential bevacizumab + IFN followed by TKIs in patients able to receive multiple lines of therapy suggest that sequential therapy could be a promising approach to improve patient outcomes in mRCC.