Genotyping guided ripretinib directly after the progression of first-line imatinib therapy in advanced gastrointestinal stromal tumor: a case report

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Surgery and tyrosine kinase inhibitor (TKI) therapy are the main choices of treatment. However, the long-term use of TKIs is prone to drug resistance. Herein, we report the case of a 47-year-old female with primary gastric GIST with liver metastases since June 2015. The patient achieved disease control under imatinib therapy and underwent primary lesion resection. She took postoperative imatinib maintenance therapy, but discontinued imatinib for 10 months about 2 years after surgery. The patient suffered from disease progression in May 2019, with recurrence of liver metastases and new abdominal metastases. From then on, imatinib was resumed and partial response (PR) persisted for another 2 years. The patient subsequently experienced tumor progression due to secondary KIT exon 17 mutation confirmed by tissue biopsy and circulating tumor DNA (ctDNA) detection. After multidisciplinary team discussion, the patient received ripretinib as a second-line therapy, and ctDNA monitoring demonstrated that the KIT mutations turned negative. After disease control from ripretinib for 2+ months, she underwent cytoreductive surgery (R0/1) and received ripretinib maintenance treatment postoperatively. We believe that this case provides a reference value for individualized ripretinib precise therapy according to mutational analysis after the progression of first-line GIST treatment, and ctDNA can predict effectiveness to guide treatment.