MIAMI – Third-line targeted therapy has demonstrated activity, is prevalent in use, and should be offered to clinically eligible patients with metastatic renal cell carcinoma (mRCC), a study presented at the 14th International Kidney Cancer Symposium 2015 (IKCS 2015) has shown.1
Because third-line targeted therapy efficacy for mRCC has not been well-characterized, it is not reimbursed by health insurance in many areas of the world, researchers sought to evaluate the effectiveness of third-line targeted therapies like everolimus, sorafenib, and sunitinib.
Researchers analyzed data from 4824 patients included in International mRCC Database Consortium (IMDC) who were treated with first-line targeted therapy. Of those, 2534 received second-line therapy and 1060 had third-line targeted therapy. Everolimus was the most commonly used third-line targeted agent with 26% of patients receiving the mTOR inhibitor, followed by sunitinib and sorafenib, both at 12%, pazopanib at 11%, temsirolimus at 10%, and axitinib at 8%.
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Patients were also classified by prognostic group per IMDC criteria. A total of 7.2% of patients had favorable risk, 65.3% of patients had intermediate risk, and 27.5% of patients had poor risk.
Results showed that the overall response rate for third-line therapy was 10.5% and 50.6% of the 563 evaluable patients achieved stable disease. Median overall progression-free survival and overall survival from third-line therapy initiation was 3.9 months (95% CI, 3.5 – 4.2) and 12.5 months (95% CI, 11.8 – 13.5), respectively.
Progression-free survival was 5.9 months (95% CI, 4.6 – 8.0) for axitinib, 4.9 months (95% CI, 3.7 – 5.8) for sunitinib, 4.6 months (95% CI, 3.4 – 6.6) for pazopanib, 3.7 months (95% CI, 3.1 – 4.7) for everolimus, 3.5 months (95% CI, 2.9 – 4.1) for sorafenib, 3.2 months for temsirolimus (95% CI, 2.5 – 3.9), and 3.2 months (95% CI, 1.4 – 5.2) for bevacizumab.
Overall survival was 19.2 months (95% CI, 13.5 – 22.7), 10.5 months (95% CI, 8.0 – 13.3), 13.7 months (95% CI, 10.2 – 17.7), 12.4 months (95% CI, 10.3 – 14.3), 12.5 months (95% CI, 10.6 – 17.1), 9.9 months (95% CI, 7.3 – 12.5), and 6.4 months (95% CI, 4.1 – 13.7), respectively.
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Researchers found that progression-free survival for favorable-risk patients was 7.5 months (95% CI, 5.7 – 12.0), 4.3 months (95% CI, 3.5 – 5.4) for intermediate-risk, and 2.6 months (95% CI, 1.9 – 3.0) for poor risk.
After adjusting for IMDC criteria, multivariate analysis showed that hazard ratios for death were not statistically significantly different between the different third-line therapies.
“Further studies are necessary to elucidate appropriate sequencing,” the authors concluded during their poster presentation. “IMDC criteria appear to stratify favorable/intermediate/poor risk patients well in the third-line targeted therapy setting.”
Reference
- Stukalin I, Wells JC, Donskov F, et al. Third Line Therapy in Metastatic Renal Cell Carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC) [abstract]. BJU Int. 2015. doi: 10.1111/bju.13365.
