Jing Zhao, Ming Zou, Jinyan Lv, Yingmin Han, Guangzhi Wang, Gang Wang

Osimertinib is commonly used in pulmonary adenocarcinoma patients who are resistant to first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and carry the T790M mutation. However, the use of osimertinib may result in the development of further resistance, most commonly via the cis-C797S mutation. Herein, we report a case of a lung cancer patient harboring triple EGFR mutations of L858R, T790M, and cis-C797S who was treated with a combination of osimertinib, bevacizumab, and brigatinib. The above 3 mutations were detected by circulating tumor DNA analysis after osimertinib treatment. Subsequently, the patient received combination therapy of osimertinib and bevacizumab; the partial relief obtained was negated by later disease progression. The regimen was then changed to osimertinib, bevacizumab, and brigatinib combination therapy. Partial remission was observed, and a significant reduction in EGFR mutations was detected. This case represents the first evidence that 1) bevacizumab combined with osimertinib can significantly relieve tumor growth and respiratory symptoms in non-small-cell lung cancer patients with osimertinib resistance and 2) the clinical use of osimertinib, bevacizumab, and brigatinib is effective as combination therapy for pulmonary adenocarcinoma in the presence of triple EGFR mutations of L858R, T790M, and cis-C797S. These combination therapies may provide potential novel treatment options for pulmonary adenocarcinoma patients.