Efficacy and safety of axitinib as third line therapy in metastatic renal cell carcinoma (mRCC): retrospective analysis

Abstract

Background: Axitinib is approved after tyrosine kinase inhibitors (TKI) failure in mRCC, and is often used in second line. Few data are available when axitinib is used in third line. The goal of the study is to report our experience with axitinib in the 3rd line setting. Method(s): Data from mRCC patients ( pts) treated at Gustave Roussy with axitinib as third line therapy have been analyzed. Prognostic factors from International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), patient characteristics, safety and outcome were collected. Result(s): 29 pts have been treated from November 2012 to February 2015. The median age was 55 years (38-73). All pts had clear cell histology. IMDC was assessed in 28 pts (77%): 5 (17%) were in the good risk group, 16 (55%) in the intermediate risk group and 7 (24%) in the poor risk group. The number of metastatic sites involved was: 1 in 2 pts (7%), 2 in 8 pts (26%), 3 in 7 pts (24%) and >3 in 12 pts (41%). As first line therapy 24 pts (83%) received TKI (sunitinb 69%), 2 (7%) bevacizumab + interferon, 1 (3%) temsirolimus and 2 (7%) clinical trial. The second line therapy was: everolimus in 17 pts (59%), nivolumab in 6 (21%), anti VEGF therapy in 6 (21%). At the time of the analysis, 11 pts (38%) are on therapy. Median PFS is 8.1 months (95% CI 5,7-10,6). 7 pts (24%) reached partial response and 19 pts (66%) achieved a stable disease, as best RECIST response. In 20 pts (69%), axitinib dose titration was feasible. At dose of 5 mg/bid 9 pts (31%) and 11 pts (38%) reported grade 1 and grade 2 adverse events (AEs) respectively, 6 (21%) pts reported grade 3 AEs. The most common grade 3 AEs reported was hypertension. At escalated dose of 7 mg/bid 14 pts (48%) and 6 pts (21%) reported grade 1 AEs, 5 (17%) grade 2 (diarrhea, fatigue, dysphonia, HFS) and 1 (3%) grade 3 (fatigue). 5 pts (17%) received the highest dose of 10 mg/bid, 2 presented grade 2 AEs (fatigue, hypertension) and 2 pts grade 3 (fatigue, HFS). One grade 4 AE was observed. 6 pts (21%) requiring dose reduction and 3 (10%) discontinued treatment because of toxicities. Among the 16 pts that discontinued treatment, 8 pts received a subsequent line of therapy. Median overall survival is not yet reached. Conclusion(s): This study confirms safety and efficacy of axitinib, even when given in the third line setting. Response rate as well as PFS suggest that efficacy is not reduced when axitinib is given in this patient population. Further prospective data are warranted.