A61: Liver toxicity associated with the use of Pazopanib in renal cancer patients: UK teaching hospital experience
1University Hospital Birmingham, Birmingham, West Midlands, UK, UK,2University of Delhi, Delhi, India
Hepatotoxicity has been observed in about 40-50% renal cancer patients treated with Pazopanib in clinical trials. We have analysed the incidence of Pazopanib induced liver toxicity in real world setting.
A retrospective analysis was conducted on metastatic renal cancer patients treated with Pazopanib between December 2010 and September 2014, within two cancer centres from Birmingham, UK. Data was collected on baseline demographics, liver toxicity and overall survival.
A total of 89 patients were identified (59 male, 30 female). Median age was 65 (range 17-91). 59 (66%) patients had prior nephrectomy. 75% of patients had PS 0-1 whereas 25% had PS 2-3. 25% patients had liver metastases. Median duration of treatment was 25.14 weeks. 34 (38%) patients were still on treatment and 50 (56%) were still alive at the time of analysis. Median OS for all patients was 17 months. 27 (30%) patients developed hepatotoxicity. 10 and 23 patients had all grades rise in bilirubin and ALT respectively whereas 4 and 6 patients had grade 3 or 4 rise in bilirubin and ALT respectively. 20 patients continued Pazopanib whereas 2 discontinued treatment temporarily and 5 discontinued Pazopanib permanently. Median duration of treatment for patients with hepatotoxicity was 34.4 weeks. Median duration of treatment before hepatotoxicity was 5.86 weeks (range 1.8 53.5). Median duration of hepatotoxicity was 7.71 weeks. 10 (37%) patients with hepatotoxicity were still on treatment. Median OS for patients with hepatotoxicity was 17.5 months. 53/89 (59.5%) patients stopped Pazopanib- 36 (40.5%) disease progression, 10 (11.2%) non-hepatic toxicity, 5 (5.6%) hepatotoxicity, 2 (2.2%) other reasons. Due to advanced age/ co-morbidities, 35 (39.3%) patients commenced treatment at a reduced dose (16 at 600mg, 19 at 400mg od). In these patients, incidence of liver toxicity did not differ from those treated with full dose.
Our data shows lower hepatotoxicity rates as compared to clinical trials. Reassuringly most of the cases were mild and settled without treatment modifications. Frequency of hepatotoxicity was not affected by age, PS or presence of liver metastases.