Updates in Management of Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are best treated with tyrosine kinase inhibitors (TKIs); however, patient- and disease-specific factors should be considered when choosing therapy, according to a presentation at the Hematology/Oncology Pharmacy Association virtual 2021 conference.

Christine Barrett, PharmD, clinical pharmacy specialist, Alleghany Health Network Cancer Institute in Pittsburgh, described current strategies for overcoming imatinib resistance in GISTs and updates in the treatment of GISTs.

GISTs account for 0.1% to 0.3% of all gastrointestinal cancers but are the most common mesenchymal tumors of the digestive tract.

“It most frequently occurs in the stomach, followed by the small intestine, the colon and rectum, and the esophagus,” Barrett said.

She noted that it is a wide spectrum of disease, with many patients undiagnosed for a long period of time until complications or metastases occurs.

There are 3 different mutations of GISTs, including KIT mutations, platelet-derived growth receptor alpha inhibitors (PDGFRA), and wild-type, with KIT being the most common. Common treatment of GISTs include surgery, medical therapy, radiotherapy, chemo-embolization, and hepatic artery embolization, with TKIs being the most notably indicated in resectable and unresectable or metastatic disease, according to Barrett.

For resectable GISTs, neoadjuvant options are considered for genotype-sensitive disease to decrease surgical morbidity using imatinib or avapritinib, whereas adjuvant options focus on imatinib for patients with intermediate or high risk of recurrence, and continuation of adjuvant imatinib is considered if taken prior to resection.

For unresectable GISTs, the introduction of imatinib revolutionized treatment.

“First-line treatment with imatinib in advanced GIST results in response or tumor control in more than 80% of patients,” Barrett said. “About 10% will progress within 3 to 6 months of initiating therapy, whereas 40% to 50% of patients will develop resistance within 2 years.”

As for overcoming imatinib resistance, whether it is primary or secondary resistance, Barrett discussed how there can be different response rates based on tumor mutation status, with 90% in KIT exon 11 mutation and 50% in KIT exon 9 mutation. The standard first-line dosing of imatinib is 400 mg daily, with adverse effects including diarrhea, edema, muscle spasms, nausea, and rash.

“For patients with documented KIT exon 9 mutation, they may benefit from dose escalation up to 800 mg, or 400 mg twice daily,” Barrett said. “Dose escalation is a reasonable option for management of secondary resistance to imatinib.”

Other treatments that Barrett discussed include sunitinib and regorafenib, and the introduction of ripretinib, which was approved in May 2020 for fourth-line treatment to overcome imatinib resistance. Even with these multiple options that exist, Barrett mentioned that when looking into TKIs, one should consider re-challenging with imatinib.

REFERENCE

Barrett C. Updates in Management of Gastrointestinal Stromal Tumors. Presented at: Hematology/Oncology Pharmacy Association 2021 virtual conference; April 15, 2021. Accessed April 15, 2021.