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Tyrosine Kinase Inhibition in Gastrointestinal Stromal Tumors

Insights From: Robert Hans Ingemar Andtbacka, MD, CM, Huntsman Cancer Institute ; Anthony P. Conley, MD, The University of Texas MD Anderson Cancer CenterSyma Iqbal, MD, UCS Norris Comprehensive Cancer Center and Hospital
Published: Tuesday, Jan 05, 2016


Although patients with gastrointestinal stromal tumors (GISTs) are commonly diagnosed with localized disease, there are some patients who present with metastatic disease, says Robert P. Conley, MD. Metastatic disease is generally confined to abdominal sites, including the liver or peritoneum, and sometimes other sites of the gastrointestinal tract. Involvement of the lymph nodes or lungs is relatively uncommon. Patients with suspected lymph node involvement should undergo tumor biopsy to confirm that symptoms are related to GIST, comments Conley.

Current FDA-approved therapies for the treatment of metastatic GIST involve tyrosine kinase inhibitors (TKIs), states Conley. The standard of care for metastatic GIST is currently imatinib, administered at 400 mg daily. It is highly recommended to consider performing mutational analysis on the KIT and PDGFR genes due to evidence suggesting that patients with KIT exon 9 mutations are likely to benefit from elevated doses of imatinib (800 mg daily).

Patients who develop resistance to imatinib within 1 to 2 years may have their imatinib dose increased from 400 mg to 800 mg or treatment switched to another TKI, such as sunitinib. Patients who become resistant within the first few months of therapy are unlikely to derive additional benefit with dose elevation, notes Conley. Third-line strategies include regorafenib, another TKI. Each of the TKIs differ in their structure and their ability to bind to different proteins, which may contribute to differences in the toxicity profiles of each agent.
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Although patients with gastrointestinal stromal tumors (GISTs) are commonly diagnosed with localized disease, there are some patients who present with metastatic disease, says Robert P. Conley, MD. Metastatic disease is generally confined to abdominal sites, including the liver or peritoneum, and sometimes other sites of the gastrointestinal tract. Involvement of the lymph nodes or lungs is relatively uncommon. Patients with suspected lymph node involvement should undergo tumor biopsy to confirm that symptoms are related to GIST, comments Conley.

Current FDA-approved therapies for the treatment of metastatic GIST involve tyrosine kinase inhibitors (TKIs), states Conley. The standard of care for metastatic GIST is currently imatinib, administered at 400 mg daily. It is highly recommended to consider performing mutational analysis on the KIT and PDGFR genes due to evidence suggesting that patients with KIT exon 9 mutations are likely to benefit from elevated doses of imatinib (800 mg daily).

Patients who develop resistance to imatinib within 1 to 2 years may have their imatinib dose increased from 400 mg to 800 mg or treatment switched to another TKI, such as sunitinib. Patients who become resistant within the first few months of therapy are unlikely to derive additional benefit with dose elevation, notes Conley. Third-line strategies include regorafenib, another TKI. Each of the TKIs differ in their structure and their ability to bind to different proteins, which may contribute to differences in the toxicity profiles of each agent.
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