Discussant of the INTRIGUE abstract, Breelyn A. Wilky, MD, Director of Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research, University of Colorado, Aurora, called the data presented “compelling evidence of the power of ctDNA [circulating tumor DNA] to identify predictive biomarkers and allow for a critical signal finding even in negative trials.” Dr. Wilky also noted, however, that sensitivity remains limited across various techniques to measure ctDNA, and clinicians are “likely missing patients who could potentially benefit from treatment.”

Nevertheless, Dr. Wilky remained enthusiastic about the potential of precision medicine to improve the outcomes of patients with advanced gastrointestinal stromal tumor (GIST). “Despite the small numbers of patients, Dr. Bauer and colleagues presented impressive differential responses to ripretinib and sunitinib, depending on specific resistance mutations identified by ctDNA,” Dr. Wilky said. “The planned, confirmatory phase III [INSIGHT] trial could impact the future of second-line standard of care.”

“The dramatic differences of sensitivity to tyrosine kinase inhibitors further cement the importance of mutation testing for just patients who are initiating tyrosine kinase inhibitor therapy but also now potentially in the second line as well,” she added.

Breelyn A. Wilky, MD

Questions Remain

However, further questions remain about how to approach patients who do not have detectable resistance mutations by ctDNA or have mutations detected by tumor biopsy. Additionally, said Dr. Wilky, despite the inclusion of these recommendations for mutation testing in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, many patients still do not ever have mutation testing performed. In terms of ctDNA testing, access and insurance coverage of liquid biopsies are still not universal across the United States and Europe.

“Overall, the role and refinement of precision medicine continue to evolve dramatically for all patients with GIST, and there is real hope for better application of better therapies at the right time for our patients,” Dr. Wilky concluded. 

DISCLOSURE: Dr. Wilky reported financial relationships with Adaptimmune Therapeutics, Adcendo, Agenus, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, Epizyme, Exelixis, Polaris, and SpringWorks Therapeutics.