A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib. Conference Paper uri icon

Overview

abstract

  • INTRODUCTION: Resistance to EGFR tyrosine kinase inhibitors develops in patients with EGFR-mutant lung cancers. New treatments are needed to address resistance not mediated by EGFR T790M; preclinical evidence suggests that the Janus kinase/signal transducers and activators of transcription signaling pathway is important in acquired resistance to EGFR-directed therapy. METHODS: We evaluated the toxicity and efficacy of erlotinib and ruxolitinib in patients with EGFR-mutant lung cancers with acquired resistance to erlotinib. Exosomes were analyzed to assess changes in relevant protein expression during treatment. RESULTS: We enrolled 22 patients: 12 patients in the phase 1 portion of the study and 10 patients in the phase 2 portion. We did not observe any dose-limiting toxicities. The maximum tolerated dose of erlotinib was 150 mg daily and that of ruxolitinib was 20 mg twice daily. The most frequent toxicities (any grade) were anemia, diarrhea, and elevation of liver function test results. One partial response was observed (5% [95% confidence interval: 0-13]). The median progression-free survival was 2.2 months (95% confidence interval: 1.4-4.1). CONCLUSION: This is the first study assessing the combination of EGFR and Janus kinase inhibition in patients with EGFR-mutant lung cancers. The combination was well tolerated but ineffective. Exosomal EGFR levels may reflect changes in tumor EGFR expression in response to therapy.

publication date

  • September 6, 2016

Research

keywords

  • Adenocarcinoma
  • Antineoplastic Combined Chemotherapy Protocols
  • Drug Resistance, Neoplasm
  • ErbB Receptors
  • Lung Neoplasms
  • Mutation
  • Neoplasm Recurrence, Local

Identity

PubMed Central ID

  • PMC5552054

Scopus Document Identifier

  • 85015292426

Digital Object Identifier (DOI)

  • 10.1016/j.jtho.2016.08.140

PubMed ID

  • 27613527

Additional Document Info

volume

  • 12

issue

  • 1