In a different prospective phase-II trial, 48 sunitinib-or bevacizumab-relapsed patients were treated with sorafenib 400 mg b.i.d. A 30% reduction of tumor burden was observed, integrated 1 PR, with a PFS of 4.four months. Most treatment-related AEs had been mild or moderate . As regards the efficacy of sunitinib right after sorafenib, pre-liminary material has been drawn from the retrospective analysis of information relevant to eight research . Zimmermann et al. evaluated 22 patients purchase Letrozole relapsed soon after the EU-ARCCS study , prospectively allocating them at relapse to suni-tinib therapy. Four individuals achieved PRs and 12 individuals achieved stable illness. The illness manage rate was 73%. The median PFS on sunitinib was 21.5 weeks, when the median OS was not reached. Estimated 1-year PFS and OS were 31 and 60%, respectively . The results of all retrospective research thinking about sorafenib immediately after sunitinib or vice versa, and which includes about 500 patients, are in agreement together with the outcomes on the prospec-tive investigations reported above and confirm the absence of cross-resistance among the two drugs . Nonetheless, it need to be underlined that the analysis on the PFSs obtained with the various drug sequences seems to indicate that the sequence sorafenib ? sunitinib could turn out to be far more favorable than the sequence suni-tinib ? sorafenib .
Such a conclusion deserves additional investigation due to the fact that a series of confounding fac- tors ? including the heterogeneity of patients accrued within the several studies, the retrospective nature on the heparin analyses, and the diverse histological kinds included ? could have provided rise to bias. As being a matter of truth, to obtain additional understanding on the optimal sequencing among sorafenib and sunitinib in mRCC, a sizable phase-III clinical study is currently ongoing . 2.2.two.two. Sunitinib just after bevacizumab. The use of sunitinib soon after bevacizumab is really a method largely recognized by the main regulatory authorities. A potential phase-II study was con-ducted so as to ascertain a lack of cross-resistance and to evaluate the safety of sunitinib in individuals with bevacizumab- refractory mRCC . The principal endpoint was ORR, while secondary endpoints included PFS, response duration, OS, and security. Out of 61 bevacizumab-refractory individuals enrolled, 32 had been also cytokine refractory. Following sunitinib therapy, 14 patients seasoned PRs last-ing 44.1 weeks , 36 had stable disease, five had progressive illness, and six individuals had been not con-sidered evaluable. Median PFS was 30.four weeks and median OS was 47.1 weeks. Following sunitinib, no distinction in ORR, PFS and OS between individuals previously receiving either first- or second-line bevacizumab-based therapy have already been observed; similar remarks can be produced as regards individuals previously treated with single-agent bevacizumab and those receiving a bevacizumab-based therapy.