Metastatic lung adenocarcinoma with HER2 V659E/amplification responding to trastuzumab deruxtecan

What happened, in summary

This 57-year-old woman was diagnosed in July 2019 with lung adenocarcinoma in the right lower lobe, with mediastinal lymph node, liver, and bone metastases. She initially refused treatment. Molecular testing showed no EGFR, ALK, or ROS1 alterations, and PD-L1 TPS was 3%, so early management did not include a standard driver-targeted therapy. In May 2020, she was admitted with severe shoulder pain, and imaging showed progression into the right middle lobe and spread to the brain, staged cT4N2M1c. She began tislelizumab, pemetrexed, carboplatin, and bevacizumab every 21 days for 6 cycles but refused local radiotherapy to the brain and bone lesions. By November 2020, CT and MRI showed a partial response, and she moved to maintenance tislelizumab plus bevacizumab. In May 2021, the lung lesions progressed while liver and brain lesions stayed stable. She received 4 cycles of tislelizumab, bevacizumab, albumin-bound paclitaxel, and carboplatin, again reaching partial response in the lung with stable liver and brain disease. Maintenance treatment then included tislelizumab, bevacizumab, and vinorelbine until March 2023, followed by bevacizumab plus vinorelbine. June 2023 imaging showed progression, so treatment changed to gemcitabine, cisplatin, and continued bevacizumab. A later biopsy found microsatellite-stable, PD-L1-negative disease with HER2 exon 17 V659E mutation and HER2 amplification. She started trastuzumab deruxtecan at 5.4 mg/kg every 3 weeks. During this treatment, nausea, vomiting, creatinine increase, white blood cell decrease, and elevated liver enzymes were grade 1-2 and managed symptomatically. By June 2024, she had a partial response that was sustained through September 2024.