Second line treatment of metastatic renal cell carcinoma: The Institut Gustave Roussy experience with targeted therapies in 251 consecutive patients

Abstract

BackgroundSequential treatment is currently the standard of care in metastatic renal cell carcinoma (mRCC). However, very little is known on how many patients (pts) can receive second line or further, and on how to predict those pts. The goal of this study was to evaluate these questions in a large series of pts treated in our institution. Patients and MethodsData from all mRCC patients treated at the IGR from 2005 to 2009 with first line targeted therapy (sunitinib (SU), sorafenib (SO), bevacizumab (B), temsirolimus or everolimus (pooled together as mammalian target of rapamycin – mTOR)) were analysed. Only patients with subsequent follow-up have been included in this analysis. Patients were defined as ‘non-eligible’ for second treatment if: they were (i) still on first line treatment, (ii) not showing progressive (durable stable disease or partial response or complete response) or (iii) if they refused a second line treatment. Results251 patients, median age 60years, median follow-up 20.2months were treated with targeted therapy with a median overall survival (OS) of 25.8months. Median OS with SU (127), SO (60) or B (61) were 26.3, 16.4 and 32.5months respectively. Only three patients received an mTOR inhibitor as first line. According to the eligibility criteria, the percentage of patients who received a second line was 59% (n=61/103), 52% (n=30/58) and 79% (n=38/48) for Su, So and B, respectively. Memorial Sloan-Kettering Cancer Centre (MSKCC) classification (P=0.02) and first line agent (P=0.001) were significant predictive factor for receiving a second line of treatment. Overall, patients receiving B were in better general condition, with 77% of performance status score (PS)=0 compared to SO (53%) and SU (48%) (P=0.005). Among the 131 patients who received a second line, the median OS from the start of second line treatment was 20.8months for a tyrosine kinase inhibitor (TKI) (n=98; 75%) and 16.6months for an mTOR (n=32; 42%) (P=0.12). Furthermore, the percentage of patients who received a third line was 56% (27/48), 28% (7/25) and 65% (13/20) for SU, SO and B, respectively. ConclusionThe median OS in patients treated with targeted therapies for mRCC in The Institut Gustave Roussy exceeds 2years. The use of second line varies from 52% to 79%. Further studies are needed to validate the MSKCC groups and first line therapy as predictive factor for second line treatment.