Reactions Weekly | 2021
Cabozantinib/osimertinib
Abstract
Acquired drug resistance and diarrhoea: case report An 81-year-old woman acquired drug resistance while receiving osimertinib. She additionally developed diarrhoea during treatment with osimertinib and cabozantinib for lung adenocarcinoma [not all duration of treatment to reactions onsets stated; routes not stated]. The woman presented to the hospital in May 2018, with a productive cough and shortness of breath for few months. Subsequently, she was diagnosed with stage IV lung adenocarcinoma and mutation observed in EGFR. Later, she received first-line therapy with osimertinib 80 mg/day. Subsequently, symptoms improved and a CT scan performed after 12 weeks revealed a partial response (PR) and the lung lesion significantly decreased. Thereafter, her disease was controlled but, after 11 months, a subsequent CT revealed an enlarged left lung mass ultradeep plasma derived circulating tumor DNA and NGS (next-generation sequencing) revealed EGFR E746_ and TP53 H179R mutation. She presented with asymptomatic disease progression (PD) (acquired drug resistance). Subsequently, the woman denied chemotherapy and osimertinib therapy was continued. In July 2019, she was readmitted with progressive aggravated clinical symptoms. Chest CT revealed the mass in the upper lobe of the left lung was enlarged and densified significantly with increased left pleural effusion which indicated PD with serious symptoms. Hence, she received intensive respiratory support with ultrasound guided pleural puncture and catheterization. Subsequently, hydrothorax exudate NGS revealed deletion of EGFR E746_ and TP53 and METD1228N missense mutation noted. Hence, her treatment changed to cabozantinib 40 mg/day plus osimertinib 80 mg/day. Subsequently, within 1 week, improvement in clinical symptoms was noted. After 10 days, a subsequent CT scan showed a primary lesion of the left lung had dramatically shrunk and efficacy was also observed as PR. After her discharged, she continued cabozantinib and osimertinib; however, she developed grade 2 to 3 diarrhoea. She had been receiving cabozantinib and osimertinib until her symptoms deteriorated again in May 2020. After 1 month, she died with a total of 25 months of survival since diagnosis [outcome of ADR not stated and cause of death not stated].