Outcomes in late-line systemic treatment in GISTs: Does sequence matter?

Abstract

11542 Background: Ripretinib (R) is approved for 4th line treatment of GIST based on superior PFS and OS compared to placebo in a phase 3 study, with RR of 11.8% and PFS of 6.3 months (mo). In addition to having high potency against PDGFRA D842V, avapritinib (A) showed activity in 4th or later lines for KIT mutated patients (pts). The RR was 17% and median duration of response was 10.2 mo from a phase 1 study. It is not known if pts receiving R benefit from A after progression or vice-versa. We retrospectively reviewed outcomes of R and A to determine if sequence affects outcomes. Methods: Pts diagnosed with GISTs and treated with both R and A at UTMDACC from Jan 2016 to Dec 2021 were included. Pts were separated into R-A (RA) or A-R sequence (AR) and outcomes were tabulated. Descriptive statistics were used to summarize characteristics and genetic profiles. Differences between RA and AR groups were calculated using Fisher’s exact. Response was evaluated using RECIST. Kaplan-Meier and Log-rank test were used to estimate and compare PFS and OS between groups. Results: Twenty pts were included in the study; 12 in RA and 8 in AR. Median age was 55 years (R:29.7-76.3). Most pts had small bowel primary (11/20, 55%) followed by stomach (4/20, 20%). All baseline characteristics and mutations were equitably distributed between RA and AR. RR of R was 17% and 14% in RA and AR groups, respectively and RR of A was 33% and 29% in RA and AR, respectively (Table). None of the pts with secondary exon 13 mutations responded to R or A. The drug administration sequence did not affect RR (p = 0.7, 0.62 in R, A). The PFS of the second drug administered, was shortened. PFS did not differ based on type of KIT mutation. Median OS from diagnosis in RA and AR groups were 121.8 (58.2-NR) and 171.3 (73.3-NR) mo, respectively and median OS from start of RA and AR was 43.9 (23.0-NR) and NR (11.5-NR) mo, respectively. Neither difference was statistically significant. Conclusions: Both R and A are efficacious in later lines of treatment, with greater benefit from the agent used first. Although, the combined PFS was numerically higher in AR compared to RA (20.5 vs 15.2 mo), the OS was not different. Currently, R is the only drug approved in the 4th or later lines in KIT-mutated GIST. [Table: see text]