VEGF-Blocker Bevacizumab + EGFR-TKI Erlotinib Delivers 72% ORR and 21-mo mPFS in Hereditary Papillary RCC

Bevacizumab (anti-VEGF antibody) plus erlotinib (EGFR tyrosine-kinase inhibitor) was tested in an open-label Phase 2 study (NCT01130519) enrolling 43 patients with fumarate-hydratase–mutated hereditary leiomyomatosis and renal-cell cancer (HLRCC)-associated papillary RCC and 40 with sporadic papillary RCC. Confirmed responses were seen in 72% of hereditary cases and 35% of sporadic cases; mPFS was 21.1 mo and 8.9 mo, respectively, with mOS 44.6 mo vs 18.2 mo. Grade ≥3 toxicity included hypertension (34%) and proteinuria (17%), alongside mostly low-grade acneiform rash (93%) and diarrhea (89%). For context, the current cabozantinib reference standard in metastatic papillary RCC shows 23% ORR and 9 mo mPFS in the SWOG S1500 trial, underscoring the doublet’s outsized activity—particularly in HLRCC, where no approved therapy exists.