HER2-positive metastatic lung cancer treated with trastuzumab deruxtecan (Enhertu)

What happened, in summary

A woman in her early 50s had undergone a right mastectomy for early breast cancer more than 10 years earlier. Five years before the metastatic recurrence, she also had a right-middle-lobe lobectomy and mediastinal lymph-node dissection for Stage IB adenosquamous lung cancer, pT2aN0M0. She did not receive adjuvant chemotherapy after either early-stage cancer.

Seven months after lung surgery, surveillance CT found a 4 mm nodule in the right upper lobe. It remained visible 6 months later. A further scan 1 year after that showed marked progression, with multiple nodules across the right upper and lower lobes and concern for lymphangitic spread. PET imaging showed activity confined to the lungs. A biopsy contained only scant tumour cells, but genomic testing identified high-level ERBB2, or HER2, amplification of at least 20 copies, together with TP53 and CDK12 alterations. The recurrence was considered most likely to arise from the more recent lung cancer rather than the remote breast cancer.

She received 4 cycles of carboplatin, pemetrexed and pembrolizumab, followed by maintenance pembrolizumab. The lung nodules enlarged 4 months after induction treatment. She declined standard second-line cytotoxic chemotherapy because of toxicity concerns but agreed to trastuzumab deruxtecan.

Treatment began at 6.4 mg/kg every 3 weeks. Persistent grade 2 nausea led to a reduction to 5.4 mg/kg from cycle 3, after which symptoms improved. At 3 months, imaging showed more than a 50% reduction in the pulmonary nodules. The response lasted 13.8 months, demonstrating meaningful disease control from HER2-directed therapy in HER2-amplified lung cancer.