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Poster Session (ID 8)
- Event: ACLC 2018
- Type: Poster Session
- Presentations: 1
- Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
P076 - A Lung Adenocarcinoma with Concomitant EGFR And De Novo MET Amplification Response Well to Combination of TKI And Bevacizumab (ID 193)
00:00 - 00:00 | Author(s): Q. Chu
Patients with NSCLC who are carrying concomitant de novo EGFR and MET amplification were commonly reported to have poor response to therapy. Here, we presented a case of a patient harboring concomitant de novo MET and EGFR, who obtained favorable response to combinatorial therapy of TKI and bevacizumab.
We presented a lung adenocarcinoma patient harboring dual EGFR-MET alterations, and evaluated his response to combinatorial therapy of TKI and bevacizumab. In vitro experiments were performed in HCC827(EGFR-19del) and HCC827-GR (EGFR-19del+MET amplification) cells to validate the effect of bevacizumab on MET pathway.
A 44-year-old male stage IV lung adenocarcinoma with left lung tumor was detected harboring of EGFR-19del and MET amplification using PCR and FISH. The patient was treated with erlotinib+bevacizumab and achieved partial response (PR) with a PFS with 13 months. After PD, NGS performed on both tissue and plasma biopsies revealed that the patients obtained first-generation resistant mutation EGFR-T790M, concomitant with EGFR-19del. The patient was treated with osimertinib+bevacizumab and achieved PR. He developed PD again with a PFS of 10.2 months, and repeated biopsies sequencing identified concomitant EGFR-19del and MET amplification. Then, the patient was treated with crizotinib+bevacizumab and the best curative effect was stable disease. Four months later, he developed PD and the third biopsy still revealed positive EGFR-19del and MET amplification. The patient received osimertinib+crizotinib+bevacizumab and he achieved PR one month after treatment initiation. He is still under the treatment and the PFS is more than eight months. In vitro data revealed that, under gefitinib treatment, cell viability was higher in HCC827(EGFR-19del) than HCC827-GR (EGFR-19del+METamp). However, the patient harboring dual EGFR-MET alterations in this study obtained a PFS of 13 months to erlotinib, similar with patients with EGFR-19del only (mPFS was 13 months to erlotinib as reported), suggesting the efficacious treatment of EGFR-TKI and bevacizumab than TKI alone. We observed that VEGFR-2 was expressed at relatively high levels in HCC827-GR than other cell line without METamp, and VEGF pathway inhibition by bevacizumab resulted in decreased phospho-c-Met in HCC827-GR cell lines. This result provided in vitro evidence that bevacizumab can reduce MET pathway activation.
This study provided basic knowledge and evidence for patients harboring concomitant EGFR and de novo MET amplification who may obtain favorable response to combinatorial treatment of TKI and bevacizumab. Encouraging antitumor activity of TKI+bevacizumab support further development of this combination for patients with advanced NSCLC and other solid tumors.