There is no standard therapy for this type of cancer, which could be sporadic or associated with germline mutations (Hereditary leiomyomatosis and renal-cell cancer) in HLRCC-associated papillary renal-cell carcinoma. Responses were observed in 72%, the median progression-free survival was 21.1 months, and the median overall survival was 44.6 months. In sporadic papillary renal-cell carcinoma 35% had responded with a median progression-free survival of 8.9 months, median overall survival of 18.2 months. This is a promising combination.
Hereditary leiomyomatosis and renal-cell cancer (HLRCC) is an inherited disorder characterized by germline pathogenic variants in the gene encoding fumarate hydratase and an increased risk of papillary renal-cell carcinoma. No effective therapy is known for patients with advanced HLRCC-associated papillary renal-cell carcinoma, and most patients die from progressive disease.
In this open-label, phase 2 study, we evaluated the efficacy of bevacizumab (10 mg per kilogram of body weight every 2 weeks) and erlotinib (150 mg once daily) in patients with advanced HLRCC-associated or sporadic papillary renal-cell carcinoma. The primary end point was overall response; secondary end points included progression-free and overall survival.
A total of 43 patients with HLRCC-associated papillary renal-cell carcinoma and 40 patients with sporadic papillary renal-cell carcinoma were enrolled. A confirmed response occurred in 31 patients (72%; 95% confidence interval [CI], 57 to 83) with HLRCC-associated papillary renal-cell carcinoma; the median progression-free survival was 21.1 months (95% CI, 15.6 to 26.6), and the median overall survival was 44.6 months (95% CI, 32.7 to could not be estimated). A confirmed response occurred in 14 patients (35%; 95% CI, 22 to 51) with sporadic papillary renal-cell carcinoma, with a median progression-free survival of 8.9 months (95% CI, 5.5 to 18.3) and a median overall survival of 18.2 months (95% CI, 12.6 to 29.3). The most common treatment-related adverse events were acneiform rash (93%), diarrhea (89%), and proteinuria (78%). The most common treatment-related adverse events of grade 3 or higher were hypertension (34%) and proteinuria (17%).
The combination of bevacizumab and erlotinib showed antitumor activity in patients with HLRCC-associated or sporadic papillary renal-cell carcinoma. Toxic effects were those known to be associated with this combination. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT01130519.)
Phase 2 study showing that SABR for RCC is safe and feasible for those who refuse or are not candidates for surgery. The median age was 77, and this seems to be a safe, noninvasive alternative.