PMC6419586_01
Copy number plot for the liver biopsy sample tested before combination therapy of osimertinib and crizotinib.. Notes: The x-axis shows the target positions (exons); the left y-axis, the log ratio; the right y-axis, gene copy number. Vertical lines indicate divisions between chromosomes (numbered at the lower left corner of each section).
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He then underwent biopsy of a liver mass and CGP revealed EGFR L858R, EGFR amplification (17 copies), MET amplification (12 copies), among other non-actionable genomic alterations (Table 1; Figure 1).
CT images showing the right apex lung mass before (A & D), 8 weeks after (B & E), and 28 weeks after (C & F) combination therapy of osimertinib and crizotinib. The red arrows indicate the right apex lung mass seen on the axial view (A-C) as well as the coronal view (D-F). CT images showing a hepatic mass before (G), 8 weeks after (H), and 28 weeks after (I) combination therapy of osimertinib and crizotinib. This patient also received microwave ablation of this hepatic mass prior to initiation of the combination therapy. MRI images showing the posterior left temporal lobe mass 18 weeks after (J) and 28 weeks after (K) combination therapy of osimertinib and crizotinib. The red circles clearly indicate disease progression at 28 weeks as demonstrated by the interval increase in size of the mass. Of note, this mass had previously received stereotactic radiation. The patient subsequently underwent total resection of the mass (L).
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He had a sustained PR as follow-up scans ~20 weeks later showed further improvement of target lesions (-32% by RECIST 1.1) (Figure 2A-I). However, despite good extracranial response after 28 weeks of combination therapy, the patient experienced CNS progression with increase in size of a pre-existing lesion (Figure 2J and K) and development of three new punctate lesions. He underwent resection of the enlarging brain metastasis (Figure 2L) and CGP performed on this tumor specimen again identified EGFR L858R, EGFR amplification (42 copies), and MET amplification (35 copies) without revealing additional mechanisms of resistance (Table 1).
Schematic summary of treatment course.. Abbreviations: CGP, comprehensive genomic profiling; CNS, central nervous system; LN, lymph node; PD, progressive disease; SRS, stereotactic radiosurgery.
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The schematic summary of treatment course is shown in Figure 3.