Repeat biopsy of growing tumors at clinical progression has become increasingly important as the results may better predict prognosis and guide therapy 15,16. Understanding the acquired resistance mechanisms is essential as new specific resistance mechanism-based therapies are becoming more common and are effective. For instance, relapsed tumors with the EGFR T790M secondary mutation or SCLC transformation can be treated by T790M-specific EGFR-TKI in clinical trial settings 17 or cytotoxic chemotherapy and radiation for SCLC 9.
Histological pathology is always the gold standard for the detection of genotyping; however, this position has been challenged recently. One primary reason is that IGH may exist in spatially separated subclones of the same tumor 24,25 and the tissue genotype may yield a false-negative result. In the research of rociletinib (CO-1686) in NSCLC patients 23, among 113 patients with plasma genotyping, there were 17 patients with T790M positivity in plasma, but nine results were negative and eight failed tissue genotyping. The rate of clinical response to rociletinib was almost identical in patients with a positive T790M mutation in plasma and tissue.
Unfortunately, the patient was not enrolled in the AURA 17 trial and did not receive AZD9291 treatment; thus, we could not evaluate the efficacy of third-generation EGFR-TKI targeting EGFR T790M mutation in this patient.
This work was supported by the Natural Science Foundation of China (81402429) and the Natural Science Foundation of Zhejiang Province, China (LQ14H160003). This study was carried out in accordance with the Declaration of Helsinki and has been approved by the ethics committee of Zhejiang Cancer Hospital. We had obtained informed consent for the publication from the patient and her husband.
There are no conflicts of interest.
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