From the Guidelines
The management of gastrointestinal stromal tumors (GISTs) involves a multidisciplinary approach combining surgery and targeted therapy, with the primary treatment for localized GISTs being complete surgical resection with negative margins, and imatinib as the first-line treatment for metastatic or unresectable GISTs, starting at 400 mg daily, with dose increases to 800 mg daily for patients with KIT exon 9 mutations, as recommended by the most recent guidelines 1.
Key Principles of GIST Management
- Complete surgical excision of the lesion with no dissection of clinically negative lymph nodes is the standard treatment for localized GISTs, with sparing surgery recommended whenever possible 1.
- Imatinib at 400 mg daily is the standard upfront treatment for locally advanced inoperable and metastatic disease, with dose increases to 800 mg daily for patients with KIT exon 9 mutations 1.
- Genetic testing for KIT and PDGFRA mutations is crucial as it guides treatment decisions, with certain mutations like PDGFRA D842V being resistant to standard imatinib therapy 1.
Treatment Algorithm
- First-line treatment: imatinib at 400 mg daily, with dose increases to 800 mg daily for patients with KIT exon 9 mutations 1.
- Second-line treatment: sunitinib at 50 mg daily for 4 weeks followed by 2 weeks off, as recommended by the guidelines 1.
- Third-line treatment: regorafenib at 160 mg daily for 3 weeks followed by 1 week off, as recommended by the guidelines 1.
Important Considerations
- Regular monitoring with CT or MRI scans every 3-6 months is essential to assess treatment response 1.
- Long-term follow-up is necessary due to the risk of late recurrence, with surveillance continuing for at least 5-10 years after initial treatment 1.
- Interventional techniques, such as radiosurgery and radiofrequency ablation, may be options in selected cases, as recommended by the guidelines 1.
From the FDA Drug Label
2 Gastrointestinal Stromal Tumors STIVARGA is indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.
2 Gastrointestinal Stromal Tumors The efficacy and safety of STIVARGA were evaluated in an international, multicenter, randomized (2:1), double-blind, placebo-controlled trial [Study “GIST Regorafenib In progressive Disease” (GRID); NCT 01271712] in patients with unresectable, locally advanced or metastatic gastrointestinal stromal tumor (GIST), who had been previously treated with imatinib mesylate and sunitinib malate.
The management of Gastrointestinal Stromal Tumor (GIST) includes treatment with regorafenib (STIVARGA) for patients with locally advanced, unresectable, or metastatic GIST who have been previously treated with imatinib mesylate and sunitinib malate 2. The recommended dose is 160 mg taken orally once daily for the first 21 days of each 28-day cycle 2.
- Key points:
- Indication: locally advanced, unresectable, or metastatic GIST
- Previous treatment: imatinib mesylate and sunitinib malate
- Recommended dose: 160 mg once daily for 21 days of each 28-day cycle
- Important considerations:
- Monitor hepatic function prior to and during treatment
- Interrupt and then reduce or discontinue STIVARGA for hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis, depending upon severity and persistence 2
From the Research
Management of Gastrointestinal Stromal Tumor (GIST)
The management of GIST involves a multidisciplinary approach, including surgery, tyrosine kinase inhibitors, and other therapies.
- For localized primary GISTs, surgical resection is the mainstay of therapy, with a 5-year survival rate of approximately 50%-65% after complete resection 3.
- Adjuvant imatinib is recommended for patients with intermediate or high-risk disease, with a goal of preventing recurrence 4, 5.
- For unresectable or metastatic GIST, tyrosine kinase inhibitors such as imatinib, sunitinib, and regorafenib are used, with imatinib being the first-line treatment 6, 3.
- Neoadjuvant tyrosine kinase inhibitor therapy can be effective for primary and recurrent/metastatic GIST, with a median duration of therapy ranging from 315 to 537 days 7.
- The optimal duration of adjuvant imatinib remains unknown, but guidelines suggest administration for at least 12 months 5.
- Cytoreductive surgery may be considered in patients with metastatic GIST who respond to imatinib, particularly if a R0/R1 resection is achieved 4.
- Radiofrequency ablation and other therapies such as ipilimumab, nivolumab, and endoscopic ultrasound alcohol ablation have shown promising results in selected cases 5.
Treatment Options
The treatment options for GIST depend on the stage and risk of the disease.
- For low-risk primary GISTs, surgical resection is the primary treatment, with adjuvant imatinib recommended for patients with a substantial risk of relapse 5, 3.
- For high-risk primary or metastatic GISTs, imatinib 400 mg daily for 12 months is recommended, with sunitinib and regorafenib used for patients with KIT exon 9,13, and 14 mutations, and highly refractory tumors, respectively 5, 6.
- For unresectable metastatic or recurrent GIST, tyrosine kinase inhibitors are the primary treatment, with imatinib being the first-line treatment, followed by sunitinib and regorafenib 6, 3.
Prognostic Factors
Several prognostic factors can impact oncologic outcomes after neoadjuvant tyrosine kinase inhibitor therapy for GIST.
- Duration of neoadjuvant therapy >365 days is associated with a higher risk of recurrence for primary GIST 7.
- KIT mutations and multivisceral resection predict shorter recurrence-free survival for all patients 7.
- Disease progression on neoadjuvant tyrosine kinase inhibitors is associated with a shorter overall survival for patients with recurrent/metastatic disease 7.