Long term toxicity of tyrosine kinase inhibitors (TKIs) in patients with metastatic clear cell renal cell carcinoma (RCC)

Abstract

16045 Background: TKIs are in common use in metastatic RCC, often given chronically. The toxicity related to the long term use of oral TKIs in metastatic RCC is not well described. Methods: Patients (pts) with clear cell metastatic RCC, receiving either sunitinib (SU), sorafenib (SOR) or, axitinib (AG), followed for at least 16 months were retrospectively identified. Data on Karnofsky performance status (KPS), response to treatment, dose modifications and, time to worst grade toxicity, were analyzed. Results: Sixteen pts received an oral TKI (SU=12, SOR=3, AG=1) for a median duration of 24.4 months (range 16.5- 46.1). Median age of pts is 61.5 yrs (range 35–70). Baseline KPS was 90 in 7 pts (44%) and 100 in 9 pts (56%).12 pts (75%) experienced a decline in KPS by 10 points and 2 pts (12.5%) by 20 points. Best response was complete response in 1 pt (6%), partial response in 10 pts (63%) and stable disease in 5 pts (31%). Overall 12% (2/16) of pts had Gr 4 toxicity, 38% (6/16) had Gr 3 toxicity, and 50% (8/16) had grade 1–2 as their worst toxicity. The median time to worst grade toxicity was 5.5 (range 0.6–28.3) months. 77% of worst grade toxicities occurred within 12 months and 23% after 12 months (see table). Two pts discontinued therapy; one due to PD and the other following a myocardial infarction. 50% (8/16) of pts had dose reductions at some point in time. Dose of SU starting at 50mg qd was reduced to 37.5mg qd in 5/12 pts and 25 mg qd in 1/12 pts respectively. Dose of SOR starting at 400 mg bid was reduced to 400 mg qd in 1/3 pts and to 400 mg qod in 1/3 pts. Conclusions: Maximum toxicity from oral TKIs is generally, but not always reached within 12 months after initiating treatment. Hypothyroidism, myelosuppression and fatigue were the most common toxicities in pts receiving treatment for longer than 12 months. Specific maximum toxicities and timing Timing of worst grade toxicity after starting treatment <12 M >12 M Pts N % N % Hypothyroidism 7 44 6 38 Anemia 2 13 3 19 Neutropenia 4 25 5 31 Thrombocytopenia 9 56 4 25 Fatigue 9 56 2 13 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Bristol-Myers Squibb, Genentech™ BioOncology, Genzyme, Onyx, Pfizer Oncology, Wyeth Bayer, Onyx, Pfizer Oncology, Wyeth Pfizer Oncology