Outcomes of Late-Line Systemic Treatment in GIST: Does Sequence Matter?

Ripretinib and avapritinib have demonstrated activity in the late-line treatment of gastrointestinal stomal tumors (GISTs). We investigated whether patients previously treated with ripretinib benefit from avapritinib, and vice versa. Patients diagnosed with metastatic/unresectable GIST and treated with both drugs at two institutions in 2000–2021 were included. Patients were grouped by drug sequence: ripretinib–avapritinib (RA) or avapritinib–ripretinib (AR). Radiographic response was evaluated using RECIST 1.1. Kaplan–Meier and log-rank tests were used to compare time-to-progression (TTP) and overall survival (OS). Thirty-four patients (17 per group) were identified, with a median age of 48 years. The most common primary site was the small bowel (17/34, 50%), followed by the stomach (10/34, 29.4%). Baseline characteristics and tumor mutations were not significantly different between groups. Response rates (RRs) for ripretinib were 18% for RA and 12% for AR; RRs for avapritinib were 12% for AR and 18% for RA. Median TTPs for ripretinib were 3.65 months (95%CI 2–5.95) for RA and 4.73 months (1.87–15.84) for AR. Median TTPs for avapritinib were 5.39 months (2.86–18.99) for AR and 4.11 months (1.91–11.4) for RA. Median OS rates following RA or AR initiation were 29.63 (95%CI 13.8–50.53) and 33.7 (20.03–50.57) months, respectively. Both ripretinib and avapritinib were efficacious in the late-line treatment of GIST, with no evidence that efficacy depended on sequencing.