The efficacy of avapritinib for unresectable or metastatic gastrointestinal stromal tumors with and without PDGFRA D842V mutations: A meta-analysis.

Abstract

834 Background: The FDA approved avapritinib for the treatment of unresectable or metastatic (UM) gastrointestinal stromal tumors (GIST) with PDGFRA exon 18 mutations. This includes the multi-drug resistant PDGFRA D842V mutation. This meta-analysis describes the efficacy of Avapritinib among all UM GIST patients with a sub-analysis that stratified for PDGFRA D842V status. Methods: PubMed and Embase were searched for studies investigating the response of GIST treated with avapritinib since 2020. Searches resulted in 473 articles after duplicates were removed. Randomized controlled trials or cohort studies enrolling patients ≥ 18 years of age and reporting response to 300 - 400 mg of avapritinib in UM GIST were included. Studies that provided ad-hoc analysis of previously published data were excluded. Meta-analysis was performed using the “meta” package version 8.2.0 in R version 4.5.1. Results: This search resulted in 6 studies (N = 635). The median age of patients included ranged from 58 to 62.8 years old. 12.1% of patients had the PDGFRA D842V mutation. The most common sites of primary tumors were the small intestine (38.4%) and stomach (25.0%). Pooled response rates to avapritinib and statistical heterogeneity according to Cochran's Q test are summarized in Table 1. Complete response rates (CR) for all patients and those without the PDGFRA D842V mutation was 0% (95% CI 0% – 0%). Partial response rate (PR) was 24% (95% CI 21% – 27%) for all patients. PR was 19% (95% CI 16% - 22%) in those without the PDGFRA D842V mutation. Among PDGFRA D842V positive patients, CR was 2% (95% CI 0% - 5%) and PR was 83% (95% CI 74 - 91). Conclusions: Although avapritinib is approved for first-line treatment for GIST with PDGFRA exon 18 mutations, few PDGFRA D842V patients achieved a CR. Future studies should compare the efficacy of avapritinib to novel therapies in PDGFRA D842V patients to identify optimal treatments. This analysis found avapritinib has low efficacy in all UM GIST and those without the PDGFRA D842 mutation. This supports the use of avapritinib as a late-line therapy for UM GIST and underscores the importance of early genetic testing to guide treatment. Efficacy of avapritinib in unresectable or metastatic gastrointestinal stromal tumors stratified by PDGFRA D842V status: A meta-analysis. Complete Response (CR)% (95% CI) CR Heterogeneity (I^2) Partial Response (PR)% (95% CI) PRHeterogeneity (I^2) Stable Disease (SD) % (95% CI) SD Heterogeneity (I^2) Progressive Disease (PD)% (95% CI) PD Heterogeneity (I^2) All Patients 0.0 (0.0 - 0.0) 0.0 24.0 (21.0 - 27.0) 97.3 37.0 (33.0 - 40.0) 92.4 14.0 (12.0 - 17.0) 95.2 PDGFRA D842V positive 2.0 (0.0 - 5.0) 0.0 83.0 (74.0 - 91.0) 24.4 11.0 (4.0 - 18.0) 0.0 2.0 (0.0 - 5.0) 0.0 PDGFRA D842V negative 0.0 (0.0 - 0.0) 0.0 19.0 (16.0 - 22.0) 45.4 40.0 (36.0 - 44.0) 89.5 29.0 (25.0 - 32.0) 45.7