Bevacizumab, Erlotinib, And Imatinib In The Treatment Of Patients With Advanced Renal Cell Carcinoma: Update Of A Multicenter Phase Ii Trial.

4594 Background: Most patients with clear cell RCC have loss of von-Hippel-Lindau (VHL) gene function, ultimately leading to overexpression of VEGF, transforming growth factor (TGF-α), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF). In this phase II trial, we evaluate the combination blockade of VEGF, and the EGF and PDGF receptors as treatment for metastatic RCC. Methods: Eligibility: metastatic clear cell RCC; 0–2 previous systemic regimens; ECOG PS 0–1; no previous anti-angiogenesis or EGF receptor inhibitor therapy; no active CNS metastases; adequate organ function; no history of thromboembolic disease; informed consent. All patients received bevacizumab 10 mg/kg IV q 2 wks, erlotinib 150 mg PO daily, and imatinib 400 mg PO daily. Patients were evaluated for response after 8 weeks; treatment continued until tumor progression. Results: 92 patients entered this trial between 6/04 and 4/05. Pertinent clinical characteristics: no previous systemic treatment, 71%; Motzer prognostic category low/intermediate/high 47%/50%/3%. 84 patients (91%) received at least 8 weeks of therapy. Objective responses were seen in 11 patients (12%); an additional 52 patients (57%) had stable disease/minor response at first reevaluation. After a median follow-up of 11 months, projected median and 1-year progression-free survivals are 9 months and 40%, respectively. One-year overall survival is 62%. The addition of imatinib to bevacizumab/erlotinib added substantial toxicity. Grade 3/4 toxicity included: diarrhea, 48%; skin rash, 27%; fatigue, 23%; nausea/vomiting, 20%. 2 patients discontinued treatment as a result of toxicity; all patients who received treatment for > 8 weeks required dose reductions of imatinib and/or erlotinib. Conclusions: The addition of imatinib, a PDGF receptor inhibitor, to bevacizumab/erlotinib does not appear to substantially improve the efficacy of the 2-drug combination. This 3-drug combination produced moderate to severe toxicity in the majority of patients, primarily exacerbations of diarrhea, fatigue, and skin rash. Further development of this 3-drug regimen is not recommended. [Table: see text]