Citation: European Journal of Cancer Supplements, Vol 7 No 2, September 2009, Page 424

T. Eisen¹, H. Joensuu², P. Nathan³, P. Harper⁴, M. Wojtukiewicz⁵, S. Nicholson⁶, A. Bahl⁷, P. Tomczak⁸, A. Wagner⁹, D. Quinn<sup>10

1</sup>Addenbrooke's Hospital, Department of Oncology, Cambridge, United Kingdom
²Helsinki University Central Hospital, Department of Oncology, Helsinki, Finland
³Mount Vernon Hospital, Medical Oncology, Northwood, United Kingdom
⁴Guy's Hospital, Medical Oncology, London, United Kingdom
⁵Bialostockie Centrum Onkologii, Oddzial Onkologii Klinicznej z Pododdzialem Chemioterapii Dziennej, Bialystok, Poland
⁶University Hospitals of Leicester, Medical Oncology, Leicester, United Kingdom
⁷Bristol Haematology and Oncology Centre, Clinical Oncology, Bristol, United Kingdom
⁸Szpital Kliniczny Przemienienia Pánskiego UM, Klinika Onkologii, Poznan, Poland
⁹Bayer Schering Pharma AG, Clinical Development Oncology 2, Berlin, Germany
¹⁰University of Southern California, Comprehensive Cancer Center, Los Angeles, USA

Background: Tyrosine kinase inhibitors have considerably changed the treatment of RCC, and several new agents are being evaluated in the search for improved therapy options. BAY 73–4506 is a potent, oral multikinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases (eg VEGFR, TIE2, PDGFR, FGFR, KIT, and RET). Following promising results in preclinical tumor xenograft models and in a Phase I study (3 weeks on/1 week off schedule), BAY 73–4506 is being investigated in a multicenter, open-label, Phase II study in previously untreated patients with metastatic or unresectable RCC (ID 11726; sponsor Bayer Schering Pharma AG).
Methods: Adult patients with previously untreated, unresectable, or metastatic, predominantly clear-cell RCC were enrolled. Other inclusion criteria were Eastern Cooperative Oncology Group performance status 0–1, low or intermediate risk (Motzer score), measurable disease according to RECIST (Response Evaluation Criteria In Solid Tumors), and adequate bone marrow and organ function. Treatment consisted of BAY 73–4506 160 mg once daily on a 3 weeks on/1 week off schedule. Study objectives were evaluation of antitumor response and safety. The primary efficacy end point was response rate (RECIST).
Results: Patient accrual was completed in October 2008 and as of April 2009, 49 patients (27 male, 22 female; median age 62 years [range 40–76]) have received ≥1 dose of BAY 73–4506. Of 48 patients evaluable for efficacy, preliminary data indicate a partial response (PR) in 33% (23% confirmed PR) and stable disease in 46% of patients. All patients were evaluable for safety. Common treatment-related adverse events (AE) (≥20% of patients, all grades) were hand-foot skin reaction (HFSR) 61%, fatigue 51%, mucositis 45%, hypertension 41%, rash 35%, alopecia 33%, diarrhea 31%, voice changes 29%, and anorexia 24%. Grade 3/4 treatment-related AEs (≥5% of patients) were HFSR 18%, fatigue 10%, hypertension 6%, rash 6%, anorexia 6%, and renal failure 6%. Renal failure occurred in patients who continued taking study medication despite having inadequate fluid intake and/or diarrhea. Twenty-six patients remain on treatment.
Conclusions: Current data indicate promising antitumor activity of BAY 73–4506 as 1st-line treatment of patients with metastatic or unresectable RCC. AEs were typical of the drug class and were manageable.