Bevacizumab and Erlotinib in Hereditary and Sporadic Papillary Kidney Cancer

作者：Ramaprasad Srinivasan, Sandeep Gurram, Eric A. Singer, Abhinav Sidana, Munjid Al Harthy, Mark W. Ball, Julia C. Friend, Lisa Mac, Erin B. Purcell, Cathy D. Vocke, Christopher J. Ricketts, Heidi H. Kong, Edward W. Cowen, Ashkan A. Malayeri, Joanna H. Shih, Maria J. Merino, W. Marston Linehan · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2200900 · 被引用次数：33 · 研究领域：Renal cell carcinoma treatment、Bladder and Urothelial Cancer Treatments、Thyroid Cancer Diagnosis and Treatment

BACKGROUND: 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. METHODS: 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. RESULTS: 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...