What happened, in summary

This 55-year-old man developed 3 months of irritating cough and sudden shortness of breath in March 2020. CT showed a left hilar lung mass, a large pleural effusion, and atelectasis. Thoracentesis relieved fluid, bronchoscopy confirmed lung adenocarcinoma, and pleural-fluid cytology showed atypical cells. Molecular testing found an EGFR exon 19 deletion, with additional alterations including AKT2, BRCA1, MYC, and TP53. The tumor was microsatellite stable with high tumor mutational burden, and the cancer was staged cT2aN2M1a, Stage IVA, because of malignant pleural effusion. He first received intrapleural cisplatin, recombinant human endostatin, and daily gefitinib. In April 2023, CT showed new left pleural effusion, and he switched to almonertinib, which reduced the effusion by October 2023. In January 2025, recurrent large left pleural effusion and atelectasis signaled progression. Pleural-fluid testing again showed EGFR exon 19 deletion, new resistance-associated alterations, PD-L1 TPS 40% and CPS 41, and low TMB. He received intrapleural endostatin and cisplatin for symptom control, then chose ivonescimab monotherapy because of toxicity concerns. Seven cycles from January to June 2025 achieved stable disease, but CT on June 30 showed progression in the left lung. He then accepted ivonescimab plus pemetrexed. As of August 2025, CT showed stable disease, brain MRI and abdominal CT showed no new metastases, and grade 2 hypothyroidism was controlled with levothyroxine. Ivonescimab monotherapy was well tolerated, without major blood-count, liver, or kidney toxicity. The later hypothyroidism appeared after combination treatment began and did not require stopping therapy, which helped him continue treatment despite multiple prior resistance events.