Bevacizumab Plus Erlotinib Combination Therapy for Advanced Hereditary Leiomyomatosis and Renal Cell Carcinoma-Associated Renal Cell Carcinoma: A Multicenter Retrospective Analysis in Korean Patients

Cancer Res Treat. 2019 Oct;51(4):1549-1556. doi: 10.4143/crt.2019.086. Epub 2019 Mar 25.

Abstract

Purpose: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare genetic syndrome resulting from germline mutations in fumarate hydratase. The combination of bevacizumab plus erlotinib showed promising interim results for HLRCC-associated RCC. Based on these results, we analyzed the outcome of bevacizumab plus erlotinib in Korean patients with HLRCC-associated RCC.

Materials and methods: We retrospectively reviewed the efficacy and safety of bevacizumab plus erlotinib in patients with HLRCC-associated RCC who were confirmed to have germline mutations in fumarate hydratase. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were progression-free survival (PFS) and overall survival (OS).

Result: We identified 10 patients with advanced HLRCC-associated RCC who received bevacizumab plus erlotinib. Median age at diagnosis was 41 years, and five of the patients had received the combination as first- or second-line treatments. The ORR was 50% and the median PFS and OS were 13.3 and 14.1 months, respectively. Most adverse events were predictable and manageable by conventional measures, except for one instance where a patient died of gastrointestinal bleeding.

Conclusion: This is the first real-world outcome of the treatment of advanced HLRCC-associated RCC. Bevacizumab plus erlotinib therapy showed promising activity with moderate toxicity. We should be increasingly aware of HLRCC-associated RCC and bevacizumab plus erlotinib should be a first-line treatment for this condition, unless other promising data are published.

Keywords: Bevacizumab; Erlotinib; Fumarate hydratase; Hereditary leiomyomatosis and renal cell carcinoma; Non-clear cell; Renal cell carcinoma.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / administration & dosage*
  • Bevacizumab / adverse effects
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / genetics
  • Erlotinib Hydrochloride / administration & dosage*
  • Erlotinib Hydrochloride / adverse effects
  • Female
  • Fumarate Hydratase / genetics
  • Germ-Line Mutation
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics
  • Leiomyomatosis / drug therapy*
  • Leiomyomatosis / genetics
  • Male
  • Middle Aged
  • Neoplastic Syndromes, Hereditary / drug therapy*
  • Neoplastic Syndromes, Hereditary / genetics
  • Republic of Korea
  • Retrospective Studies
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Survival Analysis
  • Treatment Outcome
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / genetics

Substances

  • Bevacizumab
  • Erlotinib Hydrochloride
  • Fumarate Hydratase

Supplementary concepts

  • Hereditary leiomyomatosis and renal cell cancer