Maintained sensitivity to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer recurring after adjuvant erlotinib or gefitinib Journal Article


Authors: Oxnard, G. R.; Janjigian, Y. Y.; Arcila, M. E.; Sima, C. S.; Kass, S. L.; Riely, G. J.; Pao, W.; Kris, M. G.; Ladanyi, M.; Azzoli, C. G.; Miller, V. A.
Article Title: Maintained sensitivity to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer recurring after adjuvant erlotinib or gefitinib
Abstract: Purpose: Given the unprecedented efficacy of EGFR tyrosine kinase inhibitors (TKI) in advanced EGFR-mutant lung cancer, adjuvant TKI therapy is an appealing strategy. However, there are conflicting findings regarding the potential benefit of adjuvant EGFR-TKI in patients with lung cancer harboring EGFR mutations. To better understand these results, we studied the natural history of lung cancers which recurred despite adjuvant TKI. Experimental Design: Patients with recurrent EGFR-mutant lung cancer following adjuvant TKI were identified using an Institutional Review Board-approved mechanism. Recurrent cancer specimens were tested for resistance mutations. Sensitivity to retreatment with EGFR-TKI was evaluated. Results: Twenty-two patients with cancers harboring an EGFR sensitizing mutation received adjuvant erlotinib or gefitinib for a median of 17 months (range 1-37 months). T790M was more common in cancers which recurred while receiving TKI than in those which recurred after stopping TKI (67% vs. 0%, P = 0.011). Fourteen patients who developed recurrence after stopping EGFR-TKI were retreated, with a median time to progression of 10 months and radiographic response seen in 8 of 11 patients with evaluable disease (73%). Conclusions: Recurrence of EGFR-mutant lung cancer after stopping adjuvant TKI should not preclude a trial of TKI retreatment; a phase II trial of erlotinib in this setting is underway. Studies of adjuvant EGFR-TKI will underestimate the potential survival benefit of adjuvant TKI for patients with EGFR-mutant lung cancers if retreatment at recurrence is not given. ©2011 AACR.
Keywords: adult; cancer survival; clinical article; controlled study; human tissue; aged; aged, 80 and over; middle aged; gene mutation; exon; gene deletion; mutation; histopathology; erlotinib; cancer growth; drug efficacy; drug withdrawal; treatment duration; antineoplastic agents; bone metastasis; cancer adjuvant therapy; chemotherapy, adjuvant; cancer staging; recurrent cancer; lymph node metastasis; lung neoplasms; epidermal growth factor receptor; lung cancer; recurrence; tumor biopsy; receptor, epidermal growth factor; drug resistance, neoplasm; drug hypersensitivity; protein kinase inhibitors; liver metastasis; lung metastasis; cerebrospinal fluid; drug response; gefitinib; brain metastasis; cancer relapse; quinazolines; drug sensitivity; epidermal growth factor receptor kinase inhibitor; pleura metastasis
Journal Title: Clinical Cancer Research
Volume: 17
Issue: 19
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2011-10-01
Start Page: 6322
End Page: 6328
Language: English
DOI: 10.1158/1078-0432.ccr-11-1080
PROVIDER: scopus
PMCID: PMC3186869
PUBMED: 21831955
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 2 November 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Camelia S Sima
    204 Sima
  2. Christopher G Azzoli
    105 Azzoli
  3. William Pao
    141 Pao
  4. Vincent Miller
    261 Miller
  5. Yelena Yuriy Janjigian
    145 Janjigian
  6. Marc Ladanyi
    863 Ladanyi
  7. Gregory J Riely
    344 Riely
  8. Geoffrey R Oxnard
    24 Oxnard
  9. Maria Eugenia Arcila
    336 Arcila
  10. Mark Kris
    597 Kris
  11. Samantha Lindsay Kass
    9 Kass