Three lines of targeted therapy for metastatic renal cell carcinoma (mRCC): A viable strategy?

Plný text abstraktu(odkaz vede na stránky ASCO)

Abstrakt byl publikován rovněž v Supplementu časopisu
J Clin Oncol 31, 2013 (suppl; abstr e15581)

Abstract:

Background: Sequential therapy with tyrosine kinase inhibitors (TKIs) and the mTOR inhibitor everolimus has been proposed for mRCC. The aim of the present retrospective analysis was to compare the efficacy of everolimus used after one versus two prior TKIs and to assess the progress of a defined cohort of patients (pts) through sequential lines of therapy. Methods: In the national database of mRCC pts treated with targeted agents 368 pts received everolimus as the 2nd (N=269) or 3rd (N=99) targeted agents following TKIs sunitinib or sorafenib. Survival was calculated using the Kaplan-Meier method, and the differences were assessed using the Log-rank test. Furthermore, the treatment course was evaluated in 331 mRCC pts starting 1st line therapy with sunitinib or sorafenib in 2010. The data cut-off date was October 8, 2012. Results: Progression-free survival (PFS) for everolimus in the 2nd versus the 3rd line of targeted therapy was 6.5 months (95% confidence interval [95% CI] 5.3-7.7 months) versus 6.1 months (95% CI 4.0-8.3 months), respectively (P=0.159). The incidence and profile of adverse events were similar in both lines. PFS from the start of the first targeted agent to progression on the third targeted agent was similar for pts receiving three lines of therapy using the TKI-TKI-mTOR (N=99) and TKI-mTOR-TKI (N=17) sequence: 28.5 months (95% CI 25.2-31.7 months) versus 27.2 months (95% CI 24.0-30.4 months), respectively (P=0.281). The median follow-up for the initial cohort of 331 pts treated with sunitinib or sorafenib was 20.1 months. 152 pts (46%) subsequently received a 2nd line therapy, and 82 pts (25%) died before reaching the 2nd line. Of the 152 pts receiving the 2nd line therapy, only 38 pts (11%) went on to the 3rd line, and 46 pts (14%) died before reaching the 3rd line of therapy. The remaining pts still continued on 1st line (N=50; 15%) or 2nd line therapy (N=34; 10%), were lost to follow-up (N=30; 9%), or were alive but not receiving antineoplastic treatment (N=51; 15%). Conclusions: Everolimus has similar efficacy and toxicity whether used in the 2nd or the 3rd line of targeted therapy for mRCC. A minority of mRCC pts starting the 1st line targeted treatment can be expected to reach the 3rd line therapy.