Radiographic assessment and therapeutic decisions at RECIST progression in EGFR-mutant NSCLC treated with EGFR tyrosine kinase inhibitors

Lung Cancer. 2013 Mar;79(3):283-8. doi: 10.1016/j.lungcan.2012.11.007. Epub 2012 Dec 14.

Abstract

Purpose: Advanced NSCLC harboring epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors (TKIs) typically progresses after initial response due to acquired resistance. TKIs are often continued beyond progressive disease by RECIST. We investigated the practice of continuing EGFR-TKIs after RECIST-PD via CT findings.

Methods: Among 101 advanced NSCLC patients with sensitizing EGFR mutations treated with first-line EGFR-TKIs, 70 patients had baseline and at least one follow-up CT for retrospective radiographic assessments using RECIST1.1; 56 patients had experienced PD by the data closure date of June 2011.

Results: Among 56 patients experiencing PD, 82% were female, median age was 63 years, 50% were never-smokers, 57% had distant metastasis, 57% had exon 19 deletion, and 89% were treated with erlotinib. 49 patients (88%) continued TKI therapy beyond retrospectively assessed PD. 31/32 (97%) patients who progressed by an increase in their target lesions continued TKI. 13/16 (81%) patients who progressed by appearance of a new lesion remained on TKI. 5/6 (83%) patients with both increase of target lesions and new lesion at PD continued TKI. Two patients with PD in non-target lesions discontinued therapy at PD. In 49 continuing patients, the median time from retrospectively assessed RECIST-PD to termination of TKI was 10.1 months.

Conclusions: 88% of EFGR-mutant NSCLC patients who progressed on first-line TKI continued therapy beyond RECIST-PD, which is not the single determining factor for terminating TKI in EGFR-mutant NSCLC patients. Additional radiographically defined progression criteria are needed for this population.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • DNA Mutational Analysis
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / adverse effects
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics*
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Retrospective Studies
  • Tomography, X-Ray Computed

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • EGFR protein, human
  • ErbB Receptors