Real-world evidence on first-line treatment for metastatic renal cell carcinoma with non-clear cell and sarcomatoid histologies: are sunitinib and pazopanib interchangeable?

Introduction: Non-clear cell renal cell carcinoma (nccRCC) and sarcomatoid renal cell carcinoma (sRCC) are underrepresented in clinical trials. Treatment approaches are frequently extrapolated from data of clear cell renal cell carcinoma, in which pazopanib is non-inferior to sunitinib. We aim to compare the effectiveness of first-line sunitinib and pazopanib for nccRCC and sRCC. Methods: We evaluated a retrospective cohort of patients with metastatic nccRCC and sRCC treated with first-line sunitinib or pazopanib at an academic cancer centre. Overall survival (OS), progression-free survival (PFS) and response rate were measured. Kaplan-Meier and log-rank analyses were used for time-to-event data. Cox regression was used for prognostic factors. Results: Fifty-three patients were included; 16 (30.1%) treated with sunitinib and 37 (69.9%) with pazopanib. Forty-six (86.8%) patients had nccRCC and 7 (13.2%) had sRCC. The majority had intermediate or poor International Metastatic Renal-Cell Carcinoma Database Consortium risk (93%). Median PFS was 6.6 months with sunitinib and 4.9 months with pazopanib (HR 1.75; P = 0.078). Treatment with pazopanib was associated with inferior OS in comparison with sunitinib (median OS: 30.4 months versus 8.7 months; HR 2.71, 95% CI 1.31-5.58, P = 0.007). These results were confirmed in subgroup analysis of patients with papillary, chromophobe and MiT family translocation histologies (median OS: 38.7 months versus 14.7 months; HR 3.16, 95% CI 1.20-8.29, P = 0.019). Unclassified and sarcomatoid histologies had inferior OS (median: 6.9 and 1.1 months, respectively) regardless of the treatment used. Conclusion: In this patient cohort, pazopanib was associated with inferior OS in comparison with sunitinib for metastatic nccRCC. Larger trials are ideally warranted to confirm these results.