Phase II study of erlotinib in patients with locally advanced or metastatic papillary histology renal cell cancer: SWOG S0317

J Clin Oncol. 2009 Dec 1;27(34):5788-93. doi: 10.1200/JCO.2008.18.8821. Epub 2009 Nov 2.

Abstract

Purpose: Patients with advanced papillary renal cell cancer (pRCC) have poor survival after systemic therapy; the reported median survival time is 7 to 17 months. In this trial, we evaluated the efficacy of erlotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in patients with advanced pRCC, a tumor type associated with wild-type von Hippel Lindau gene.

Patients and methods: Patients with histologically confirmed, advanced, or metastatic pRCC were treated with erlotinib 150 mg orally once daily. A RECIST (Response Evaluation Criteria in Solid Tumors) response rate (RR) of > or = 20% was considered a promising outcome. Secondary end points included overall survival and 6-month probability of treatment failure.

Results: Of 52 patients registered, 45 were evaluable. The overall RR was 11% (five of 45 patients; 95% CI, 3% to 24%), and the disease control rate was 64% (ie five partial response and 24 stable disease). The median overall survival time was 27 months (95% CI, 13 to 36 months). Probability of freedom from treatment failure at 6 months was 29% (95% CI, 17% to 42%). There was one grade 5 adverse event (AE) of pneumonitis, one grade 4 thrombosis, and nine other grade 3 AEs.

Conclusion: Although the RECIST RR of 11% did not exceed prespecified estimates for additional study, single-agent erlotinib yielded disease control and survival outcomes of interest with an expected toxicity profile. The design of future trials of the EGFR axis in pRCC should be based on preclinical or molecular data that define appropriate patient subgroups, new drug combinations, or potentially more active alternative schedules.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / chemistry
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary
  • ErbB Receptors / analysis
  • ErbB Receptors / antagonists & inhibitors*
  • Erlotinib Hydrochloride
  • Female
  • Humans
  • Kidney Neoplasms / chemistry
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Receptor, ErbB-2 / analysis
  • Survival Rate
  • Von Hippel-Lindau Tumor Suppressor Protein / analysis

Substances

  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • Von Hippel-Lindau Tumor Suppressor Protein
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • VHL protein, human

Grants and funding