Therapeutically targetable mutation changes in lung adenocarcinoma metastasis.

e20719 Background: Use of targeted therapies was reported to contribute to the sharp decline of annual mortality from NSCLC in the U.S. between 2013 and 2016. However, it only benefits patients who harbor specific mutations. At present, NCCN clinical practice guidelines only recommend that when a patient's cancer progresses after initial targeted treatment, plasma or tissue-based mutation testing should be considered to understand the resistance mechanisms. Patients with prior negative findings are rarely re-biopsied and re-profiled genomically when metastases develop. Methods: We conducted analyses on applying 449 paired samples from 197 patients to examine targetable mutation changes in therapy–actionable genes during metastasis. We assessed targetable mutation changes in therapy–actionable genes, including KRAS, ALK, ROS1, BRAF, MET, RET, ERBB2 and NTRK, during metastasis. Results: During metastasis, 38.3% of patients receiving prior targeted therapy exhibited targetable mutation change in therapy–actionable genes, whereas 16.9% patients who never received targeted therapy also developed those changes. Stratification analysis showed that during spread from the primary tumor to metastases, 16.9% of patients exhibited such changes and 16.7% patients with paired samples of metastases across different sites had such changes. During metastasis, targeted therapy significantly increased targetable mutations in EGFR (P = 0.00006), but had no significant effect on other therapy–actionable genes. Conclusions: Among patients not receiving targeted therapy, a substantial percentage of therapeutic targetable mutations can change during metastasis. Therefore, in clinical practice, re-biopsy of metastases with genomic re-profiling should be recommended to patients when metastases develop, even if they never had prior positive results of targetable mutation testing.