Dose escalation of ripretinib can lead to response in advanced gastrointestinal stromal tumor patients refractory to the standard dose: a report of two cases

Despite an initial response, most metastatic gastrointestinal stromal tumor (GIST) patients will ultimately be refractory to all current therapies, including imatinib, sunitinib, and regorafenib. Ripretinib at 150 mg daily was recently approved as an additional line of treatment. Few options remain after ripretinib. Here we report two cases with responses to dose escalation of ripretinib after progressing on the standard dose. Case 1: A 25-year-old man was diagnosed with a kit exon 9 mutated small intestine GIST after presenting with abdominal pain. The tumor was resected, but a year later, he developed metastases to the liver and pelvis. Over the course of three years, he received multiple lines of therapies as his disease progressed, including imatinib, sunitinib, and regorafenib. He was then placed on ripretinib 150 mg daily. However, he had disease progression after two months. Ripretinib was increased to 150 mg twice a day, which he tolerated well. After three months, he had regression of his disease. Case 2: A 54-year-old male was diagnosed with an unresectable kit exon 11 mutated gastric GISTs after presenting with abdominal pain. Imatinib led to an 80% regression, allowing surgical excision. A year later, his disease recurred. Over the course of 5 years, due to multiple recurrences, he received two additional surgeries, with imatinib, sunitinib, regorafenib, and avapritinib on either the adjuvant or neoadjuvant setting. Ultimately, he developed a metastatic GIST to the left suprarenal region, retroperitoneum, and epigastric region. He was then started on ripretinib 150 mg daily, experiencing progression of his disease in three months. Ripretinib was escalated to 150 mg twice a day, which he tolerated well, and after three months, he had a regression. Dose escalation of ripretinib leads to response in patients that progressed after the standard dose, and it is well-tolerated, being a promising new treatment option in advanced GIST.