PMC6830466_01
Tumour molecular profiling and treatment strategy. Sequential therapeutic strategy of ALK tyrosine kinase inhibitors (TKI) and chemotherapy over the course of time together with detected molecular findings in patient tissue and plasma. FISH, fluorescent in situ hybridisation; MAF, mutant allele frequency; NGS, next generation sequencing.
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F1
Molecular analysis of the lung biopsy was performed, detecting an EML4-ALK translocation via fluorescent in situ hybridisation (ZytoVision) (figure 1). Crizotinib was discontinued and ceritinib followed by alectinib were given successively (figure 1), however, with very short duration of responses. Subsequently, treatment with targeting agents was switched to chemotherapy with six cycles of carboplatin and pemetrexed (figure 1), resulting in short-term disease stabilisation. Technology (ThermoFisher); testing revealed the presence of a G to A point mutation in exon 23 of the ALK gene that results in G1202R substitution of the ALK tyrosine kinase receptor (figure 1). The patient was then given lorlatinib, a third-generation TKI for patients with NSCLC who carry ALK rearrangement mutations who have progressed after receiving ALK-targeted drugs (first or second-generation TKIs). Treatment with lorlatinib delayed disease progression for 5 months. ALK point mutation, G1269A resulting from a G to C nucleotide change in exon 25, which was observed in 3.5% of reads (figure 1).