A multicenter prospective trial of sorafenib in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) refractory to prior sunitinib or bevacizumab
2008; Lippincott Williams & Wilkins; Volume: 26; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2008.26.15_suppl.5123
ISSN1527-7755
AutoresDale R. Shepard, Brian I. Rini, J. Garcia, Thomas E. Hutson, Paul Elson, Timothy D. Gilligan, Cheryl Nemec, Richard D. Lopez, D. Borner, Robert Dreicer, Ronald M. Bukowski,
Tópico(s)Renal and related cancers
Resumo5123 Introduction: Bevacizumab and sunitinib are common initial therapies for pts with mccRCC. The activity and tolerability of sorafenib in pts with mccRCC refractory to these agents was studied prospectively. Methods: Pts with mccRCC with disease progression by RECIST criteria after treatment with bevacizumab or sunitinib (two independent cohorts) received sorafenib 400 mg BID in a multicenter, prospective, phase II trial. Tumor burden reduction rate (TBRR), the proportion of pts with ≥ 5% reduction in the sum of RECIST-defined target lesions without other progression, was the primary endpoint. A two stage accrual design was utilized to test the hypothesis that the TBRR was > 20% versus < 5%. Results: Thirty-seven pts (n=31 evaluable) refractory to bevacizumab (n=13) or sunitinib (n=18) have been enrolled with 68% males, a median age of 64, 55% ECOG PS 0 and 84% with prior nephrectomy. Pts had received bevacizumab or sunitinib for a median of 8.5 months (range, 0.4–24.6). The median delay between stopping bevacizumab or sunitinib and beginning sorafenib was 4.4 weeks (range, 2.1–59.1). No objective responses were observed. Fifteen of 29 evaluable pts (52%) had some tumor shrinkage with ≥ 5% shrinkage in 11 pts (TBRR 38%) and ≥ 20% shrinkage in 4 pts (14%). TBRR was 33% and 41% in pts with prior bevacizumab or sunitinib, respectively. There were no significant correlations between response to prior therapy and tumor shrinkage in this trial. Median PFS is 3.8 months. Toxicities included hand foot syndrome (grade 1/2: 38%, grade 3: 31%), rash (20%, 7%), hypertension (28%, 14%), diarrhea (48%, 7%) and fatigue (38%, 17%). Overall, fifty-eight percent of pts had Grade 3 toxicity. Pts with prior bevacizumab had more hand-foot-syndrome (p=0.02) and mucositis (p=0.04) while pts with prior sunitinib had more rash (p=0.04). Conclusions: Administration of sorafenib is feasible in mccRCC pts previously treated with either bevacizumab or sunitinib, although associated with toxicity. Reduction of tumor burden was observed in pts receiving sorafenib with mccRCC refractory to bevacizumab or sunitinib. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Pfizer Oncology, Wyeth Bayer, Pfizer Oncology, Wyeth Bayer, Celgene, Genentech™ BioOncology, GlaxoSmithKline, Novartis, Pfizer Oncology, Wyeth
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