Stage IV ERBB2-Mutated Lung Adenocarcinoma With Brain Metastases and Multiple Targeted Therapies

What happened, in summary

A 36-year-old Asian woman who had never smoked was diagnosed with Stage IV lung adenocarcinoma after presenting with a large left pleural effusion and lung masses. Testing found an ERBB2 exon 20 insertion, and HER2 amplification was also reported. She first received carboplatin, pemetrexed and bevacizumab followed by maintenance pemetrexed and bevacizumab, with initial improvement before progression after 4.5 months. Erlotinib on a clinical trial was followed by rapid progression within 1 month. Afatinib 40 mg daily then produced improvement, but the cancer progressed after about 5 months of clinical benefit. Vinorelbine plus trastuzumab produced a partial response before progression after 6 months. Docetaxel plus trastuzumab briefly stabilized the disease, followed by progression in the lungs and adrenal gland. Ado-trastuzumab emtansine, nivolumab and a CNS-active chemotherapy trial were each followed by further progression. During this period she required 3 rounds of stereotactic radiation for brain lesions and later whole-brain radiation as new brain metastases appeared. A final rechallenge with afatinib plus bevacizumab produced a mixed response at 6 weeks, followed by liver progression after 3 months.