BERKELEY, CA (UroToday.com) - The management of metastatic renal cell carcinoma has been revolutionised in recent years with the availability of systemic therapies targeting tumour angiogenesis and other specific activating mechanisms.
However, unlike conventional chemotherapy, these agents are associated with a spectrum of toxicity with which clinicians will need to become familiar.
We report on the outcomes of metastatic renal carcinoma patients treated with anti-angiogenic targeted therapies and mTOR inhibitors at two Australian sites. Overall, both time to treatment failure after first and second line therapy (TTF1 and TTF2) and overall survival (OS) were comparable to results of published clinical trials and international case series. The only baseline variable consistently related to OS, TTF1 and TTF2 was time from diagnosis to treatment >12 months, a crude measure of the natural history of disease. We also add to the growing literature on the adverse prognostic role of systemic inflammation in renal cell carcinoma, with the finding that baseline neutrophilia was independently associated with both poorer OS and TTF1 in our cohort. Analysis of patients treated with anti-angiogenic therapy in the first-line setting demonstrated substantial improvements in both TTF1 and OS among patients developing hypertension - replicating the findings of others that treatment-related hypertension may be predictive of treatment efficacy.
Our cohort experienced the expected class-related toxicities. Agents were well tolerated with low rates of grade 3 and 4 toxicity and no treatment-related deaths. Low-grade nausea, fatigue, anorexia and diarrhoea were common, and attention should be given to these symptoms given the potential impact on quality of life in this palliative setting. Class-related toxicities of the angiogenesis inhibitors were also common, with hypertension on treatment developing in over one-third of patients treated with these agents. Given that this response may be predictive of outcome, clinicians must become familiar with its management. Our paper provides some practice pointers to aid clinicians managing this and other class-related toxicities of targeted therapies. We also describe 2 cases of potentially serious toxicity related to targeted therapies, namely symptomatic cardiac failure with anti-angiogenic therapy and pneumonitis with an mTOR inhibitor. In both instances the patients were safely and effectively re-challenged with these agents.
Overall, our retrospective study reports an Australian experience with targeted therapies for renal cell carcinoma in a real world setting. With comparable survival and toxicity outcomes to published clinical trials, it provides practical guidance to clinicians involved in the care of these patients.
K. Webber,1,2 A. Cooper,4 H. Kleiven,4 D. Yip4,5 and D. Goldstein1,3 as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
1Department of Medical Oncology, Prince of Wales Hospital, 2School of Medical Sciences and 3Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, 4Medical Oncology Unit, The Canberra Hospital and 5ANU Medical School, Australian National University, Canberra, Australian Capital Territory, Australia