Biomarker Analysis Shows Better Outcomes for Undetectable ctDNA in GIST

Jonathan C. Trent, MD, PhD, professor and associate director for Clinical Research at Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the molecular analyses of the INTRIGUE study (NCT03673501), which was supported by Caris Life Science’s Precision Oncology Alliance, investigating patients with gastrointestinal stromal tumors (GIST) that were presented at the 2023 American Society of Clinical Oncology Annual Meeting (ASCO).

Trent presented research on circulating tumor DNA (ctDNA) in the study, which randomly assigned patients with GIST resistant to imatinib (Gleevec) to receive ripretinib (Qinlock) or sunitinib (Sutent). Across both arms, ctDNA was detectable in 77.3% of patients versus 22.7% in which it was not detectable.

Those who had undetectable ctDNA had superior progression-free survival (PFS) and overall survival (OS) regardless of treatment arm. Median OS was not reached for these patients, compared with a median OS of 28 months for those who did have detectable ctDNA. Trent says these patients tend to be approximately 10 years younger and were a distinguishable population.

When investigating the 2 treatment arms, there was no statistically significant difference in PFS based on ctDNA status depending on which treatment they received. The overall results of the study did not find superior PFS for ripretinib versus sunitinib, but ripretinib showed favorable tolerability, making it a second-line option for patients who cannot tolerate sunitinib. Trent suggests this biomarker may help physicians decide how urgent it is to start the next line of therapy.

TRANSCRIPTION:

0:08 | At ASCO this year, there were several publications looking at molecular subsets of patients from the INTRIGUE study. Those subsets included patients with exon 17 or 18 resistance mutations, but also our study that looked at ctDNA in patients on the INTRIGUE study who were randomized to sunitinib or ripretinib. We asked the question of whether or not ctDNA could be a biomarker for patient outcomes. We looked at whether or not ctDNA was detected in about 77% of patients, or not detected in about 23% of patients. We honed in on those 23% of patients that did not have any ctDNA detected. We looked at their outcomes and we found that their PFS and their OS were statistically better than patients who had their ctDNA detected.

1:19 | In fact, at the time of this analysis, the OS had not even been reached yet for the patients without detectable ctDNA, whereas the patients [who] had the detectable ctDNA had a median overall survival of 28 months. So, who are these patients? We looked in a little more detail and we found that they tended to be younger patients, about 10 years younger, on average, [and they] were the patients without detectable ctDNA. It does seem to be providing a biomarker.

1:57 | We also looked at whether ctDNA detectability predicted response to ripretinib versus sunitinib. Essentially, we found that there was no statistically significant difference, which we take to mean that patients with ctDNA not detected can benefit equally from ripretinib and sunitinib. It shouldn't be a deterrent to treatment, but it is a favorable biomarker so that maybe you don't have to rush into the next line of therapy.