Avastin - Abstract 40: Systemic therapy and novel targeted therapies in renal cancer
Citation: European Journal of Cancer Supplements Volume 3, No. 2, October 2005, Page 12
M. Gore
Royal Marsden Hospital, London, United Kingdom
Renal cell carcinoma has always been considered a chemo-resistant disease and data from the 1980s suggests that response rates are very low.
There have however, only been limited data on the newer cytotoxic agents and more recently, non randomised trials have suggested that some patients may respond to combination treatments such as gemcitabine plus capecitabine.
It is becoming increasingly recognised that renal cell carcinoma is not a single disease entity.
Histology subtype and specific molecular abnormalities may not only define the behaviour of individual tumours but may also have therapeutic relevance.
This is best exemplified in relation to targeted therapies. Hormone treatments have for many years been used as second-line treatment in patients who have failed first–line immunotherapy or as initial therapy in those unfit for immunotherapy.
They are associated with low response rates and randomised trials suggest that at least, at first-line these treatments confer little or no benefit.
Standard therapy involves immunotherapy with either interferon or interleukin 2.
There are randomised data that support the use of interferon and non-randomised data that suggest high dose bolus interleukin 2 is associated with durable complete remissions in a small percentage of patients.
There is no evidence that combination immunotherapy is associated with an overall survival benefit.
Case-controlled studies and a recent randomised trial from the French cooperative group show that immunotherapy is of no benefit to patients with intermediate or poor prognosis disease.
There is something of a revolution taking place in the treatment of renal cell carcinoma and a number of new targeted agents have shown activity in this disease.
The most notable activity and best data produced so far involves Sutent and Sorafenib, the multi targeted tyrosine kinase inhibitors and Avastin, the monoclonal antibody directed against VEGF.
Sutent has shown response rates of nearly 40% in two consecutive phase 2 trials.
These studies have involved 160 patients and this makes these data of great interest.
Similarly, Sorafenib has shown significant activity in second-line with a doubling of progression-free survival.
These are particularly impressive data as the trial was randomised; patients with stable or responding disease were randomised to continue on Sorafenib or placebo.
Avastin has an overall response rate of 10% and at higher doses, a statistically significant prolongation of progression-free survival in a randomised trial against placebo.
Other targeted agents that have shown activity include Temsirolimus and infliximab.
Trials in the first-line setting are currently underway with Sutent, Sorafenib and Temsirolimus being compared to interferon.
Avastin has been combined with interferon and is being compared to single agent interferon.
These agents and other targeted compounds are being combined and further data are awaited.
Within the next 12–24 months we will have a clearer picture of the precise efficacy of these novel agents, particularly in comparison to interferon. Positive results from these studies will beg many questions: will these new agents replace interferon or will they be given in combination with it?
Which targeted agents should be combined and will that be a better strategy than administering them sequentially?
Do these compounds with their relatively good toxicity profile, open up therapeutic options for those patients with poor prognostic features who are currently considered unfit for active treatment?
Can we now start developing maintenance strategies? We are entering a new therapeutic era in renal cell carcinoma and it is imperative that we now conduct a series of well-designed trials to precisely define how these new compounds can best be utilised. |
