PMC10339383_01
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).
fmed-10-1168220-g001.jpg
PMC10339383_01_fmed-10-1168220-g001.jpg
fig1
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
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.
fmed-10-1168220-g002.jpg
PMC10339383_01_fmed-10-1168220-g002.jpg
fig2
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.
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).
fmed-10-1168220-g003.jpg
PMC10339383_01_fmed-10-1168220-g003.jpg
fig3
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).
Timeline of the treatment of the patient.
fmed-10-1168220-g004.jpg
PMC10339383_01_fmed-10-1168220-g004.jpg
fig4
The timeline of the treatment of the patient is presented in Figure 4.