Dr Somaiah on Mutation-Specific Therapy in Gastrointestinal Stromal Tumors

“Before you start a patient on a TKI for [the management of] GIST, you must know their mutational subtype. Even if you start them on imatinib, at least send off, if not the full panel, the primary KIT and PDGFRA mutation testing.”

Neeta Somaiah, MD, a professor and chair of the Department of Sarcoma Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed the landscape of mutation-specific therapy for the treatment of patients with a gastrointestinal stromal tumor (GIST).

Before initiating therapy with a TKI such as imatinib (Gleevec), a patient’s mutational subtype must be known, Somaiah began. At least primary KIT and PDGFRA mutational testing must be performed, if not a full next-generation sequencing (NGS) panel, she continued.

Mutational status testing is crucial because there are certain subsets of patients with GIST for whom imatinib will not be effective, Somaiah noted. However, a majority of patients will respond to treatment with frontline imatinib, she added.

Mutation-specific therapy is gaining a larger role in the imatinib-resistant setting, Somaiah said. Depending on the primary and secondary mutations of the disease, there may be greater benefit with one agent vs another, she continued. Most of the late-stage clinical trials in the GIST space are focused on developing agents with better outcomes compared with sunitinib (Sutent) in the second-line setting and beyond, she explained. Agents are being developed for patients harboring specific mutations as are those with broader coverage, she said.

The most common secondary mutations in patients with GIST are KIT ATP binding pocket mutations in exons 13 and 14, Somaiah said. Patients with KIT exon 13 and 14 mutations usually experience better disease control with sunitinib, she said. Patients with KIT activation loop mutations in exons 17 and 18 should be considered for treatment with regorafenib (Stivarga) or ripretinib (Qinlock), she added.

Knowing a patient’s mutational status in the post-imatinib setting helps to personalize therapy, Somaiah emphasized. Giving an effective drug in this setting can open the possibility for surgery and broader disease control, she added. On the other hand, giving a less effective agent in this setting can lead to increased resistance and disease growth, she concluded.