This single group phase II study (maximum, n=99) used axitinib (starting dose 5mg BID) in patients with metastatic clear cell RCC unsuitable for cytoreductive nephrectomy. The primary endpoint was proportion of patients alive and free of disease progression (using RECIST v1.1) at 6 months of follow-up. Secondary endpoints included toxicity, progression free survival, overall survival and correlation of biomarkers (at screening and from biopsy at progression and on treatment at 9 weeks) to the study endpoints. There were 65 patients recruited between October 2012 and December 2016 at which time the steering committee recommended closure of the trial. According to Motzer criteria, 74% of patients had intermediate risk disease and 22% had high risk disease. The most common reasons for being deemed unsuitable for cytoreductive nephrectomy included burden of metastatic disease and locally advanced primary tumor. 60% of patients were alive and progression free at the 6-month mark and 12% of patients proceeded to nephrectomy after a median of 8.6 months. Median progression free survival was 8.5 months and median overall survival was 18.7 months. There were no serious adverse events, although 51% had hypertension on treatment. Importantly, 98% of patients had biomarker specimens collected at screening, 96% on treatment, however only 12% at the time of progression secondary to patients being deemed unfit for biopsy. DNA and RNA sequencing of samples is currently underway.
In conclusion, the authors note that based on this phase II study, axitinib appears to be well tolerated and effective for the treatment of patients with mRCC where cytoreductive nephrectomy is not immediately indicated. Axitinib appears to have a 3 month longer median progression free survival than temsirolimus, which is currently recommended as standard of care for poor risk patients. Finally, embedded collection of tissue, blood and urine will allow investigation into potential biomarkers of sensitivity and resistance to axitinib.
Speaker: Grant Stewart, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK
Co-Authors: James Morden, Ekaterini Boleti, Naveen Vasudev, Fiona Thistlethwaite, Agnieszka Michael, Lucy Kilburn, Rebecca Lewis, David Nicol, Linda Pyle, Claire Snowdon, Rachel Todd, Lucy Tregellas, Samra Turajlic, Charlie Swanton, Judith Bliss, James Larkin
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA