Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification

Figures & data

Figure 1 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).

Table 1 List of genomic alterations detected from three different metastatic sites over the clinical course

Timing	Initial diagnosi	Pre-combination therapy	28 Weeks after combination therapy
Specimen site	Lymph node	Liver	Brain
Driver mutations	EGFR L858R EGFR amplification – equivocal (7 copies)	EGFR L858R EGFR amplification (17 copies) MET amplification (12 copies)	EGFR L858R EGFR amplification (42 copies) MET amplification (35 copies)
Associated mutations	CCNE1 amplification – equivocal	CDK6 amplification MYC amplification – equivocal CCNE1 amplification NFKBIA amplification – equivocal	CDK6 amplification MYC amplification CCNE1 amplification IRS2 amplification NFKBIA amplification NKX2-1 amplification RAD21 amplification
MSI	N/A	Stable	Stable
TMB (Muts/Mb)	3 (low)	4 (low)	10 (intermediate)

Abbreviations: MSI, microsatellite instability; Muts/Mb, mutations per megabase; N/A, not available; TMB, tumor mutational burden.

Figure 2 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).

Figure 3 Schematic summary of treatment course.

Abbreviations: CGP, comprehensive genomic profiling; CNS, central nervous system; LN, lymph node; PD, progressive disease; SRS, stereotactic radiosurgery.