Is an Effective Treatment for Hereditary and Sporadic Papillary Kidney Cancer at Hand?

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary condition caused by germline mutations in the fumarate hydratase gene, which increase the risk for an aggressive papillary renal cell cancer that lacks effective therapy. In preclinical studies using HLRCC models, blockade of both vascular endothelial growth factor (VEGF) receptor and epidermal growth factor receptor (EGFR) provided significant antitumor activity. Now, investigators have conducted an open-label, phase II trial of the combination of the VEGFA blocker bevacizumab and the EGFR blocker erlotinib in 40 patients with sporadic papillary renal cell carcinoma and 43 patients with HLRCC-associated papillary renal cell carcinoma. The primary end point was overall response rate.

Patients with HLRCC had a median age of 43 years compared with 56 years in the sporadic arm. Approximately one third of all patients had received at least one prior line of therapy. During a median follow-up of 72 months in the HLRCC group and 64 months in the sporadic-carcinoma group, the overall response rate was 72% (including 2 with complete response) in the HLRCC group and 35% in the sporadic-carcinoma group. In the HLRCC group, the median progression-free survival was 21.1 months, 15 patients continued therapy for more than 2 years, and the median overall survival was 44.6 months. Adverse events were consistent with the side effect profile of these two agents: Rash, diarrhea, and proteinuria were most common.