title: Delay of treatment change after objective progression on first-line erlotinib in epidermal growth factor receptor-mutant lung cancer.
abstract: BACKGROUND
  Erlotinib is a highly active epidermal growth factor receptor (EGFR) kinase inhibitor that is approved for first-line use in lung cancers harboring EGFR mutations. Anecdotal experience suggests that this drug may provide continued disease control after patients develop objective progression of disease (PD), although this has not been systematically studied to date.
  
  
  METHODS
  Patients who had Response Evaluation Criteria In Solid Tumors-defined PD who were participating in 3 prospective trials of first-line erlotinib in advanced lung cancer were studied retrospectively, and the progression characteristics were compared between patients with and without EGFR-sensitizing mutations. Factors were studied that influenced the time until treatment change (TTC), defined as the time from PD to the start of a new systemic therapy or death. The rate of tumor progression was assessed by comparing tumor measurements between the computed tomography scan obtained at the time of PD and the preceding scan.
  
  
  RESULTS
  In total, 92 eligible patients were studied, including 42 with and 50 without an EGFR-sensitizing mutation. The EGFR-mutant cohort had a slower rate of progression (P = .003) and a longer TTC (P < .001). Among the patients with EGFR-mutant cancers, 28 (66%) continued single-agent erlotinib after PD, and 21 (50%) were able to delay a change in systemic therapy for >3 months; only 2 patients received local debulking therapy during that period. Multivariate analysis of the patients with EGFR-mutant tumors demonstrated that a longer time to progression, a slower rate of progression, and a lack of new extrathoracic metastases were associated with a longer TTC.
  
  
  CONCLUSIONS
  A change in systemic therapy commonly can be delayed in patients with EGFR-mutant lung cancer who objectively progress on first-line erlotinib, particularly in those with a longer time to progression, a slow rate of progression, and a lack of new extrathoracic metastases.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Peter C
authors: PC
authors: Lo
authors: Department of Biostatistics, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts.
authors: Suzanne E
authors: SE
authors: Dahlberg
authors: Department of Radiology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
authors: Mizuki
authors: M
authors: Nishino
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Bruce E
authors: BE
authors: Johnson
authors: Department of Medicine, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts.
authors: Lecia V
authors: LV
authors: Sequist
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: David M
authors: DM
authors: Jackman
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Pasi A
authors: PA
authors: Jänne
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Geoffrey R
authors: GR
authors: Oxnard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D061665:Time-to-Treatment / Q000706:statistics & numerical data*; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors
keywords: disease progression; epidermal growth factor receptor mutation; erlotinib; non-small cell lung cancer; time until treatment change