843P - Long-term safety with axitinib in advanced renal cell carcinoma

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Renal Cell Cancer
Biological Therapy
Presenter Subramanian Hariharan
Citation Annals of Oncology (2014) 25 (suppl_4): iv280-iv304. 10.1093/annonc/mdu337
Authors S. Hariharan1, W.G. Roberts2, Z. Askerova3, B. Escudier4, J. Tarazi5, B. Rosbrook6, R.J. Motzer7, B.I. Rini8
  • 1Global Medical Affairs, Pfizer Oncology, 10017 - New York/US
  • 2Safety Strategy Risk Management, Pfizer Inc, Groton/US
  • 3Wsr Sepgr Ser Pssr Medical Writing, Pfizer Inc, Collegeville/US
  • 4Medical Oncology Department, Institut Gustave Roussy, Villejuif/FR
  • 5Clinical Development, Pfizer Oncology, San Diego/US
  • 6Clinical Statistics, Pfizer Oncology, San Diego/US
  • 7Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 10128 - New York/US
  • 8Department Of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland/US



Axitinib is approved globally in patients with advanced renal cell carcinoma (RCC) who failed one prior therapy. Although tyrosine kinase inhibitors have been available to treat RCC since 2005, long-term safety data are limited. Here we report long-term safety results with single-agent axitinib in advanced RCC, using pooled data from 14 clinical trials conducted from Apr 2002 to Oct 2013.


In the 14 studies included, starting dose of oral axitinib was 5 mg twice daily continuously. Dose interruptions and modifications were allowed per protocols. Common, long-term, treatment-emergent adverse events (AEs) were identified in patients who received axitinib ≥2 yr; these AEs were then evaluated in all patients. Analyses conducted were 1) interval analysis of AEs over successive treatment periods (0– < 6 mo, 6 mo– < 1 yr, 1– < 2 yr, and ≥2 yr) with each AE counted once per interval, 2) cumulative analysis of AEs (0– < 6 mo, 0– < 1 yr, 0– < 2 yr, and 0– ≥ 2 yr), and 3) latency analysis for time to onset of the most frequent AEs.


As of Oct 2013, 1304 patients with solid tumours, including 672 with advanced RCC, received single-agent axitinib in phase I-III studies. Among patients with RCC, 108 (16%) received axitinib ≥2 yr. In these patients, common AEs were most frequently reported within the first 6 mo of treatment, with rates stable or decreasing over time (Table). Rates of proteinuria, peripheral oedema, and elevated blood creatinine increased over time. Similarly, by cumulative analysis, most AEs analysed were reported within the first 6 mo–1 yr of treatment, with few new cases reported thereafter. Based on interval analysis, rates of common grade ≥3 AEs decreased over time with the exception of increased amylase and myocardial infarction. Table. Interval analysis of the most common AEs in patients with advanced RCC treated with axitinib ≥2 yr (n = 108).

AE 0– < 6 mo 6 mo– < 1 yr 1– < 2 yr ≥2 yr
Diarrhoea 53% 53% 45% 32%
Fatigue 38% 15% 19% 13%
Proteinuria 11% 10% 19% 11%
Decreased appetite 27% 16% 16% 9%
Hypertension 58% 16% 19% 9%
Weight loss 28% 27% 25% 9%


In patients with RCC, rates of most AEs were stable or declined after prolonged axitinib treatment. Results did not indicate that sustained exposure to axitinib is associated with unanticipated or more severe AEs.


S. Hariharan, W.G. Roberts and Z. Askerova, J. Tarazi and B. Rosbrook: is an employee of and owns stock in Pfizer Inc.; B. Escudier has served as an advisor for Bayer, Pfizer, and Novartis, and has received honoraria from Bayer, Roche, Pfizer, Genentech, Novartis, and AVEO; R.J. Motzer: has served as an advisor for Pfizer, Genentech, and AVEO, received research funding from Pfizer, Novartis, and GlaxoSmithKline, and provided paid expert testimony for Pfizer; B.I. Rini: has served as an advisor for and received research funding from Pfizer.