PMC8349191_01
Medication strategy and disease conditions of the patient during treatment. (A) An illustrated summary of the treatment received by the patient. (B) Thoracic CT images of primary lung lesions and MRI images of brain metastatic lesions during sequential ALK-TKI treatment. Tumors are indicated by red frames.
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A 46-year-old male with no smoking history was diagnosed with stage IVB LSCC (cT2bN2M1c) with three brain metastases in May 2017 (Supplementary Figure 1). A computed tomography (CT) scan and magnetic resonance imaging (MRI) indicated a 4x5 cm dense mass in the right lung and metastatic lesions in the brain, respectively (Figure 1B, Baseline). After an initial partial response (PR) was achieved (Figure 1B, Crizotinib PR), the patient exhibited a progression-free survival (PFS) of 17 months (Figure 1A). In October 2018, the size of the brain lesions increased and a new lung lesion was observed (Figure 1B, Crizotinib PD), thus, indicating progressive disease (PD). The patient achieved a complete response (CR) for the lung lesion and a PR for the brain lesions (Figure 1B, Brigatinib CR & PR). In September 2019, the disease progressed again with a PFS of 11 months (Figure 1A). ALK G1202R (MAF = 0.2%) mutation, in addition to the EML4-ALK fusion (MAF = 0.1%) (Table 1). A third-line treatment with loratinib was administered at a dose of 100 mg and achieved a PFS of 7 months (Figure 1A). However, within 2 months of initiating this therapy, additional symptoms developed, indicating PD (Figure 1A). After 2 months of treatment (Figure 1A), the disease progressed and in addition to the EML4-ALK (MAF = 0.1%) and ALK G1202R (MAF = 0.1%) mutations in the plasma, new mutations were again identified by NGS targeting 139 cancer-related genes, including ALK D1203N (MAF = 0.3%), SMARCA4 R1243W (MAF = 0.3%), and TP53 P152L (MAF = 0.3%) (Table 1).  Following this treatment, the patient achieved SD with a sustained and ongoing response for 2 months (Figure 1A).