Margaret von Mehren, MD

Case Overview: A 68-Year-Old Man With GIST

GIST Diagnoses and Risk of Recurrence

GIST: Treatment Considerations

GIST: Second-Line Treatment Options

Resistance to TKI Therapies in GIST

GIST: Third-Line Treatment Considerations

The INVICTUS Trial in GIST

Safety and Efficacy of a Newer TKI for Fourth-Line GIST

GIST: Treating With Ripretinib

Utilizing Newer TKIs to Treat GIST

GIST: Future Treatment Landscape

Case: A 68-Year-Old Man With Gastrointestinal Stromal Tumor

A 68-year-old man complains of a 5-month history early satiety and vague abdominal pain

PMH: hypertension, medically controlled; colonoscopy at age 55 unremarkable; no family history of cancer

PE: diffuse abdominal pain on palpation; otherwise unremarkable



Labs: Hb 10.1 g/dL, plt 100 x 109/L; other lab values WNL

Endoscopy: showeda submucosal ~ 5 cm mass with ulceration

EUS-FNA biopsy: irregular borders on extraluminal surfaces of the stomach with evidence of heterogeneous echogenicity

Biopsy showed gastrointestinal tumor with mitotic activity showed >5 mitoses/50 HPFs

Abdominal/pelvic CT confirmed a 5.4 cm lesion in the body of the stomach

MRI showed evidence of peritoneal metastases

He was started on imatinib 400 mg PO qDay, continued for 26 months until he complained of increased abdominal pain and decreased appetite

ECOG 1; Imatinib was discontinued due to progressive disease

Treatment with sunitinib 50 mg PO qDay for 4 weeks, with a 2-week drug-free interval was started

Treatment was well tolerated for 9 cycles when he developed an altered sense of taste, occasional vomiting and diarrhea; sunitinib was discontinued

Regorafenib 160 mg (four 40 mg tablets) PO qDay for the first 21 days of each 28-day cycle was started and tolerated except for hand-foot syndrome

Regorafenib was discontinued on progression of disease

The patient was started on ripretinib 150 mg PO qDay

Videos

Margaret von Mehren, MD, describes the rationale for treating a man with GIST with ripretinib as fourth-line therapy.

A 68-Year-Old Man With Gastrointestinal Stromal Tumor

Margaret von Mehren, MD, chief in the Division of Sarcoma Medical Oncology and physician director of the Clinical Trials Office at the Fox Chase Cancer Center, discusses ripretinib (DCC-2618) and how it works in patients with heavily pretreated advanced gastrointestinal stromal tumors (GIST).

Ripretinib is unique because of its mechanism of action, according to von Mehren. Most of the other therapies used for the treatment of patients with GIST bind the kinase and try to prevent adenosine triphosphate (ATP) from binding and leading to activation of the kinase. Most kinases require ATP for activation because it blocks the binding.

For ripretinib to become activated, on the other hand, there is a structural change, or activation loop that moves, says von Mehren. The way that this drug works in patients, is it binds the activation loop and the cite it would move into and holds them so that it can’t become activated. She explains the ripretinib works by a different mechanism than most drugs used for these patients.

Ripretinib was investigated in the phase III INVICTUS trial for patients with GIST who have received prior anticancer therapies (NCT03353753).

Margaret von Mehren, MD, discusses ripretinib and how it works in patients with heavily pretreated advanced gastrointestinal stromal tumors.

Margaret von Mehren, MD | Authors

Articles

A 68-Year-Old Man With Gastrointestinal Stromal Tumor

How Ripretinib's Mechanism of Action Works in Patients With GIST