PMC9675326_01
Diagram of patient's treatment history and clinical course. (A) Timeline of treatment; (B) Change of tumor lesions upon the combined treatment with dabrafenib, trametinib and lorlatinib. The arrow denotes pericardial or pleural effusion; Two months after the treatment beginning, both pericardial and effusions declined; lung lesion remained stable; Three months after the treatment beginning, the arrow denotes the increased pleural effusion, lung lesion remained stable.
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The immunohistochemical assay showed PD-L1 expression of 10% (TPS) (Figure 1A).  In Oct 2018, the patient started 1st-line treatment with pemetrexed combined with cisplatin (AP), lasting for three cycles, and the disease was stable (Figure 1A). The treatment was switched to lorlatinib (100mg qd) combined with bevacizumab (400mg triweekly), and the disease was stable After a PFS of 7 months on 3rd-line treatment, the patient was detected with pericardial and pleural effusions (Figure 1B), and a PD was determined in Oct. 2021. A CT scan in Jan 2022 showed reduced pericardial and pleural effusions and a stable lung lesion (Figure 1B).
IGV illustration of ROS1 novel fusion and potential drug-resistant mutations. (A)
MED13L-ROS1(M1:R34); (B)
NF1 p.G127Ter; (C)
BRAF, c.1799T > A, p.V600E; (D)
NRAS, c.182A>G, p.Q61R.
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NGS using a 168-gene panel (Burning Rock Biotech, Guangzhou, China). NGS identified a novel fusion MED13L-ROS1 (Figure 2A) co-occurring with a common EZR-ROS1 (Table 1). NGS with her pericardial effusion sample revealed the emergence of BRAF p.V600E mutation (Figure 2C), retention of the two ROS1 fusions, and the disappearance of NF1 p.G127Ter. The result showed the acquisition of NRAS p.Q61R (Figure 2D), NTRK amplification, and CDKN2A deletion, as well as the disappearance of FGF19, FGF4, and FGF3 amplifications (Table 1).