Original Articles
Local Therapy with Continued EGFR Tyrosine Kinase Inhibitor Therapy as a Treatment Strategy in EGFR-Mutant Advanced Lung Cancers That Have Developed Acquired Resistance to EGFR Tyrosine Kinase Inhibitors

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Background

Development of acquired resistance limits the utility of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for the treatment of EGFR-mutant lung cancers. There are no accepted targeted therapies for use after acquired resistance develops. Metastasectomy is used in other cancers to manage oligometastatic disease. We hypothesized that local therapy is associated with improved outcomes in patients with EGFR-mutant lung cancers with acquired resistance to EGFR TKI.

Methods

Patients who received non–central nervous system local therapy were identified by a review of data from a prospective biopsy protocol for patients with EGFR-mutant lung cancers with acquired resistance to EGFR TKI therapy and other institutional biospecimen registry protocols.

Results

Eighteen patients were identified, who received elective local therapy (surgical resection, radiofrequency ablation, or radiation). Local therapy was well tolerated, with 85% of patients restarting TKI therapy within 1 month of local therapy. The median time to progression after local therapy was 10 months (95% confidence interval [CI]: 2–27 months). The median time until a subsequent change in systemic therapy was 22 months (95% CI: 6–30 months). The median overall survival from local therapy was 41 months (95% CI: 26–not reached).

Conclusions

EGFR-mutant lung cancers with acquired resistance to EGFR TKI therapy are amenable to local therapy to treat oligometastatic disease when used in conjunction with continued EGFR inhibition. Local therapy followed by continued treatment with an EGFR TKI is well tolerated and associated with long PFS and OS. Further study in selected individuals in the context of other systemic options is required.

Key Words

EGFR-mutant lung cancer
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors
Metastasectomy
Local therapy

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Disclosures: Dr. Riely has consulted for AstraZeneca, Boehringer Ingelheim, Chugai, Ariad, Tragara, Daiichi, Novartis, Abbott Molecular, and Celgene, and has received grants from Infinity Pharmaceuticals, Bristol-Myers Squibb, Novartis, Chugai, Pfizer, Merck, and GlaxoSmithKline. Dr. Riely has also had travel expenses covered by Bristol-Myers Squibb. Dr. Solomon has consulted for Johnson and Johnson and Covidien, and has received grants from GE Healthcare and AngioDynamics. Dr. Miller is currently employed by and owns stock in Foundation Medicine. Dr. Miller also has a patent issued from Molecular T790M for detection of EGFR T790M. Dr. Krug has consulted for Genentech. Dr. Kris has received grants from Pfizer and Boehringer Ingelheim, and has consulted for Pfizer, Boehringer Ingelheim, Genentech/Roche, Millenium Pharmaceuticals, Bind Biosciences and Covidien. The other authors declare no conflicts of interest.