Authors reply: an adjusted indirect comparison of everolimus and sorafenib therapy in sunitinib-refractory metastatic renal cell carcinoma patients using repeated matched samples

The consistency of our results compared with other publications was called into question. As stated in our paper [1], the progression-free survival (PFS) and overall survival (OS) estimates we present are based on updated November 2008 data from the RECORD-1 trial. This is in contrast to the paper by Motzer et al. [2], which relied upon data with follow-up only through February 2008. Using updated data presents the possibility for longer survival estimates given additional observed data. The OS and PFS estimates should therefore not necessarily be expected to be identical to those presented by Motzer et al. [2]. It should also be noted that the analysis performed was a post-hoc analysis independent of the original RECORD-1 study design, and, as such, slightly different criteria to define a patient as sunitinib-refractory resulted in a sample size of 127, compared with the 124 in the original clinical trial analysis. The aim of this analysis was not to reproduce results from the Motzer et al. paper, and comparisons against their analysis were not included in our paper.

With regard to the methodology employed, this is a novel matching sampling technique with the goal of creating more comparable study populations prior to indirect comparisons of survival estimates. By using a matching technique, we were able to provide a less biased comparison of survival between the two populations treated with everolimus [2] and sorafenib [3]. Confusion about our analysis not using studies with a common comparator was also noted. Although this is typically requisite for indirect comparisons using relative efficacy measures, our analysis used an absolute estimate of survival to allow for a comparison given the available data; however, the author of the letter is correct in that a common comparator would provide additional validation of a successful match. This publication is one of the first publications highlighting our method, but a similar indirect treatment comparison method was recently published by Signorovitch et al. [4]. Known limitations of our method are provided in our paper.

The aim of this indirect analysis was to address important clinical questions in the absence of a head-to-head clinical trial; however, our work should not be misconstrued as an attempt to provide a substitute for such a head-to-head trial. The techniques were employed to reduce the influence of bias. Our study suggests that in light of the results obtained in our paper, everolimus could be preferred to sorafenib in patients pretreated with sunitinib.

Declaration of interest

Funding for this research has been provided by Novartis Pharmaceuticals Corp. E Malangone, R Casciano, J Willet, and S Sherman are employees of Analytica International, a company that received funding from Novartis Pharmaceuticals Corp. to complete this analysis and manuscript. G Di Lorenzo received honoraria from Novartis Pharmaceuticals Corp. for his involvement in this indirect analysis. C Buonerba and S De Placido have no conflict of interest to disclose and received no payment for their part in the preparation of this manuscript. X Wang and Z Liu are employees of, and own stock in, Novartis Pharmaceuticals Corp.

Acknowledgements

Editorial assistance was provided by A Perrin, an employee of Analytica International. Funding for the work was provided by Novartis Pharmaceuticals Corp. These data in the original paper were presented in part at the American Society of Clinical Oncology Annual Meeting, 4 – 8 June 2010, Chicago, IL and at the European Society for Medical Oncology 35th Annual Congress, 8 – 12 October 2010, Milan, Italy.