Efficacy of everolimus in patients with advanced renal cell carcinoma refractory or intolerant to VEGFR-TKIs and safety compared with prior VEGFR-TKI treatment, "Beyond the Abstract," by Renpei Kato, MD

BERKELEY, CA (UroToday.com) - Our study reported that median progression-free survival (PFS) and overall survival (OS) were much better than those of the RECORD 1 study, and we wanted to investigate why this was the case.

We performed univariate and multivariate analyses on PFS and OS with respect to the prognostic factors in the RECORD-1 trial (KPS, sex, age, MSKCC risk score, time from initial diagnosis, number of organs involved, sites of metastases (liver, lung, bone, lymph nodes, CNS), prior therapy (radiation, interferon, interleukin), number of prior medications, prior sunitinib, prior sorafenib, and laboratory data (corrected calcium, alkaline phosphatase, LDH, hemoglobin, platelets, neutrophils)). As for PFS, we identified poor performance status and presence of bone metastasis as significant predictors on univariate analysis, but these was not significant on multivariate analysis. As for OS, we identified poor PS, presence of bone metastasis, presence of lymph node metastasis, history of interferon treatment, and high corrected calcium level as significant predictors on univariate analysis, but we found none of them to be independent factors on multivariate analysis.

VEGFR-TKI treatment failure is an indication of everolimus therapy, and this population consists of patients who are refractory or those who are intolerant to VEGFR-TKI treatment. We considered intolerance or being refractory to prior VEGFR-TKI therapy to be a potentially important factor. We thus conducted a subanalysis by dividing the patients into a VEGFR-TKI refractory group and a VEGFR-TKI intolerant group. When we conducted the subgroup analysis on VEGFR-TKI intolerant and VEGFR-TKI refractory groups, we speculate the survival difference between our study and RECORD-1 may be attributed to two factors. First, compared to the VEGFR-TKI intolerant subgroup (16%; 45/277 cases) in the everolimus + BSC group of RECORD-1 trial, the proportion of VEGFR-TKI intolerant group in our study was much higher (58%; 11/19 cases). It is noteworthy that the frequencies of hematological toxicity and adverse events were higher in the VEGFR -TKI intolerant group than in the VEGFR- TKI refractory group before everolimus treatment, while the KPS in both groups was maintained during everolimus treatment. The frequency of hematological toxicity and adverse events tended to increase in patients on long-term treatment in both groups (data not shown in the present article). Although the response rate to everolimus is lower than that to VEGFR-TKI, the adverse event profiles of the two drugs are different. Therefore patients who are intolerant to VEGFR-TKI have good tolerability to everolimus.

Second, up to June 2012, another group of 18 patients with VEGFR-TKI treatment failure (refractory or intolerant) were switched to BSC (sorafenib in 6, sunitinib in 12) by the decision of the physicians. The reasons for discontinuing VEGFR-TKI were disease progression (10 cases), adverse events (7 cases), and economic reason (1 case). Comparing the switch to BSC after VEGFR-TKI group and our study group that received everolimus after VEGFR-TKI, the median OS in the BSC group was apparently shorter than everolimus group (10.9 (1.5-28.7) months vs not reached at 90 months). Switching to BSC or everolimus treatment was decided by the clinical doctors. Together with the small number of patients and selection bias, these factors may have influenced the results of PFS and OS in our study.

Written by:
Renpei Kato, MD 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.

Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-shi, Iwate 020-8505, Japan

Efficacy of everolimus in patients with advanced renal cell carcinoma refractory or intolerant to VEGFR-TKIs and safety compared with prior VEGFR-TKI treatment - Abstract

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