case_images: PMC10339383_01
case_images: Chest computed tomography (CT) scans before and after treatment. First-line treatment baseline (A). Five months after icotinib plus anlotinib therapy (B). Seven months after icotinib plus anlotinib therapy (C). Second-line treatment baseline (D). One month after KNO046 plus pemetrexed and carboplatin therapy (E). Forty days after three cycles of KNO046 plus pemetrexed and carboplatin therapy (F). Third-line treatment baseline (G). 1.5 month after afatinib plus docetaxel therapy (H). Fourteen months after afatinib plus docetaxel therapy (I).
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case_images: fig1
case_images: A computed tomography (CT) scan revealed several lymph node metastases in the right supraclavicular area, mediastinum, and lung, in addition to a mass in the upper lobe of the right lung, right pleural metastasis and multiple nodules in both lungs, with a high probability of inflammatory lesions combined with some metastases (Figure 1A). According to the response evaluation criteria for solid tumors (RECIST v1.1), significant lung tumor lesions decreased and developed cavity-like alterations after 5 months of therapy, demonstrating partial response (PR) (Figure 1B). The upper lobe of the right lung had a noticeably larger tumor lesion on 5 January 2021, which was classified as progressing disease (PD) using the RECIST v1.1 assessment criteria (Figure 1C). The patient opted to participate in a clinical study as the second line of treatment, receiving three cycles of KN046 (a bispecific antibody inhibitor of PD-L1 and CTLA-4) with pemetrexed 800 mg/d1 and carboplatin 750 mg/d1, with an effectiveness rating of SD on CT scan (Figures 1D,E). Forty days after discontinuation of the regimen, the patient was evaluated as PD (Figure 1F), with a significant increase in serum tumor biomarkers. Third-line therapy involved the use of afatinib 40 mg every day in conjunction with docetaxel 110 mg every 3 weeks (Figure 1G). On CT, the patient was assessed for a partial response after two cycles of therapy (Figure 1H), with no drug-related adverse events and a decrease in serum tumor biomarkers once again. August 2022, the patient underwent a CT examination which revealed a significant re-enlargement of the tumour and was considered to be drug resistant again, getting a progression free survival (PFS) of 14 months (Figure 1I). A repeat CT-guided puncture biopsy of the lung lesion and repeat NGS testing of the patient's blood and tumor specimen suggested the presence of a
case_images: Pathological diagnosis of the right supraclavicular lymph node biopsy (A). Immunohistochemistry staining: TTF-1 (B) and CK7 (C) were positive, consistent with adenocarcinoma of pulmonary origin.
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case_images: TTF-1(+), and P40(-) immunohistochemistry results were consistent with adenocarcinoma of pulmonary origin (Figure 2). The patient was found to have T4N3M1a stage IVa lung adenocarcinoma.
case_images: NGS test result showing the EGFR exon 19 p.E746_A750del (A), TP53 exon 8 p.R273C (B), and EGFR exon 20 p.T790M (C).
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case_images: fig3
case_images: Further blood and tumor specimens from the patient were subjected to next-generation sequencing (NGS) testing, showing EGFR exon 19 deletion (Figure 3A) with an abundance of 2.4% in tumor specimens and TP53 exon 8 mutation (Figure 3B) with an abundance of 0.9% in tumor specimens. T790M mutation in exon 20 of EGFR (Figure 3C). The patient is currently being treated with osimertinib (Osimertinib, a third-generation EGFR-TKI that targets EGFR mutations and T790M-resistant mutations and inhibits tyrosine kinase phosphorylation by creating a covalent bond with the C797 residue at the ATP binding site of EGFR mutations and T790M mutations, acting as a tumor suppressor).
case_images: Timeline of the treatment of the patient.
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case_images: The timeline of the treatment of the patient is presented in Figure 4.