Sequencing or not sequencing multikinase inhibitors in kidney cancer: this is the dilemma
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EDITORIAL
Sequencing or not sequencing multikinase inhibitors in kidney cancer: this is the dilemma Chiara Paglino • Camillo Porta
Published online: 9 February 2010 Springer-Verlag 2010
With the recent development of targeted therapies (Sorafenib, Sunitinib, Temsirolimus, Bevacizumab plus Interferon-a, Everolimus and now also Pazopanib) patients with advanced renal cell carcinoma (RCC) now have a wide range of treatment options, all of which have shown both relevant clinical activity and manageable safety profile. This abundance of active treatments, coupled with relatively limited information, we have gathered from registrative phase III trials have raised the question of how to use these agents optimally. Indeed, since presently, a cure for advanced RCC is definitely out of sight—despite the improvements made so far—the goal of therapy should be to extend progressionfree survival (PFS) while maintaining a patient’s quality of life. To achieve such a goal, sequencing of novel agents is a therapeutical strategy that is becoming more and more popular in everyday’s clinical practice, being mainly supported by the retrospective evaluation of several case series. Therefore, a recent prospective study reported by Di Lorenzo et al. [1] on the sequential use of Sorafenib following Sunitinib failure in metastatic RCC patients should be regarded as an extremely intriguing report. On the basis of a non-extraordinary time-to-progression (TTP) of just 16 weeks, the authors concluded that ‘‘… although well tolerated, Sorafenib shows limited efficacy in Sunitinib-refractory mRCC’’.
C. Paglino C. Porta (&) Medical Oncology, I.R.C.C.S. San Matteo University Hospital Foundation, Piazzale C. Golgi 19, 27100 Pavia, Italy e-mail: [email protected]
In our opinion, these conclusions should be reconsidered in a broader perspective on the light of all the evidence presently available on this hot topic. Indeed, in the past few years, a number of retrospective studies [2–11], together with a single prospective report [12], and the subgroup analysis of Sorafenib’s European Union and United States (US) expanded access programs [13, 14], have been published or presented in abstract form, dealing with the sequential use of the two multikinase inhibitors Sunitinib and Sorafenib (Fig. 1). Even though highly biased by their retrospective nature (and indeed, the prospective nature of the Di Lorenzo’s study is the major strength of this study), it is hard to disregard the findings deriving by all these reports, first because they collected more than 550 patients as a whole, and second because there is a constance in the results reported by different studies, performed by different groups, in different parts of the world. From the analysis of these studies, it is evident that following the failure to one multikinase inhibitors, further PFS/TTP benefit is attainable switching to the other drug; furthermore, all these study seem to suggest a somewhat strange, but intriguing finding, i.e., a longer overall PFS with the Sorafenib–Sunitinib seq
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