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" |
