Sunitinib Treatment for Patients with Advanced Clear-Cell Renal-Cell Carcinoma after Progression on Sorafenib

Abstract

Background: Sorafenib and sunitinib are tyrosine kinase inhibitors with largely overlapping specificities, approved for the treatment of metastatic renal-cell carcinoma (RCC). It was unclear whether the similarities of the two drugs would lead to complete cross-resistance, or whether sequential application would be efficacious. Methods: Patients with metastatic RCC and progression on sorafenib treatment were treated with repeated cycles of sunitinib, 50 mg for 4 weeks, followed by a 2-week break. Response (Response Evaluation Criteria in Solid Tumors, RECIST) was assessed every second cycle. Results: A total of 22 patients with progression on sorafenib were accrued. Initially, sorafenib treatment was efficacious in all patients, with 7 showing partial response (PR) and 15 stable disease (SD), and subsequent disease progression. With 4 PRs (18%) and 12 SD (55%) a disease control rate of 73% was achieved. The median progression-free survival (PFS) on sunitinib was 21.5 weeks; median overall survival (OS) was not reached. Estimated 1-year PFS and OS were 31 and 60%, respectively. There was no apparent relationship between response to sorafenib and outcome on sunitinib. Conclusion: In our cohort of patients with RCC and progression after initial efficacy of sorafenib, the efficacy data of second-line sunitinib were close to published results of first-line treatment, suggesting limited clinically relevant cross-resistance.

Tyrosine kinase inhibitor treatments in patients with metastatic thyroid carcinomas: a retrospective study of the TUTHYREF network

“…Similarly, in renal cell cancer, the efficacy of second-line sunitinib treatment was close to that of first-line therapy, suggesting limited crossresistance (16), and comparable PR rates were shown with cabozantinib and lenvatinib in both DTCs and MTCs in first-and second-line treatment (12,17,18,19). This analysis was limited by the small number of DTC patients treated with sunitinib: four patients in first-line treatment and five patients in second-line treatment.…”

Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

“…There are prospective data, although limited, that suggest a lack of total cross resistance between TKIs, either sorafenib followed by sunitinib failures or vice versa-an observation that is consistent with their differences in target specificities and slightly different toxicity spectra that sometimes permit tolerance of one agent over another. [147][148][149][150][151] Sunitinib is considered a category 2A subsequent therapy option.…”

Kidney Cancer

“…Prospective data, although limited, suggest a lack of total cross-resistance between tyrosine kinase inhibitorseither sorafenib followed by sunitinib failures, or vice versa-an observation that is consistent with their differences in target specificities and slightly different toxicity spectra that sometimes permit tolerance of one agent over another. [70][71][72][73][74][75][76] Sorafenib and sunitinib are considered category 1 by the panel when used after cytokine therapy and category 2A when used after a prior tyrosine kinase inhibitor therapy.…”