Bevacizumab and Erlotinib in Hereditary and Sporadic Papillary Kidney Cancer

N Engl J Med. 2025 Jun 19;392(23):2346-2356. doi: 10.1056/NEJMoa2200900.

Abstract

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 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%).

Conclusions: 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.).

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / adverse effects
  • Carcinoma, Renal Cell* / diagnosis
  • Carcinoma, Renal Cell* / drug therapy
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / mortality
  • Erlotinib Hydrochloride* / administration & dosage
  • Erlotinib Hydrochloride* / adverse effects
  • Female
  • Humans
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Kidney Neoplasms* / diagnosis
  • Kidney Neoplasms* / drug therapy
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / mortality
  • Leiomyomatosis* / diagnosis
  • Leiomyomatosis* / drug therapy
  • Leiomyomatosis* / genetics
  • Leiomyomatosis* / mortality
  • Male
  • Middle Aged
  • Neoplastic Syndromes, Hereditary* / diagnosis
  • Neoplastic Syndromes, Hereditary* / drug therapy
  • Neoplastic Syndromes, Hereditary* / genetics
  • Neoplastic Syndromes, Hereditary* / mortality
  • Progression-Free Survival
  • Response Evaluation Criteria in Solid Tumors
  • Skin Neoplasms
  • Treatment Outcome
  • Uterine Neoplasms

Substances

  • Bevacizumab
  • Erlotinib Hydrochloride

Supplementary concepts

  • Hereditary leiomyomatosis and renal cell cancer

Associated data

  • ClinicalTrials.gov/NCT01130519