Abstract 1630P
Background
Avapritinib (AVA) is a highly selective, potent inhibitor of KIT and PDGFRA mutant kinases, approved in the USA for unresectable or metastatic (U/M) GIST with PDGFRA exon 18 mutations, and has clinical activity in PDGFRA D842V-mutant GIST, against which approved TKIs in the European Union are not active.
Methods
This retrospective, indirect analysis compared the clinical efficacy of AVA in patients (pts) with PDGFRA D842V-mutant GIST (NAVIGATOR phase 1/2 study; NCT02508532) with the efficacy of commercially available TKIs for U/M GIST in pts from a retrospective natural history study (Study 1002). Primary endpoint was overall survival (OS) from start of reference treatment (AVA vs first TKI); secondary endpoint was progression-free survival (PFS) per modified RECIST version 1.1 criteria. Unadjusted and adjusted Kaplan–Meyer (K–M) survival curves were compared by log rank test and Cox regression-based test, respectively.
Results
In total, 56 (NAVIGATOR) and 19 (Study 1002) pts with PDGFRA D842V-mutant GIST were evaluated; the two groups’ patient characteristics were fairly balanced for sex, tumour anatomical location and duration of disease, when adjusted for imbalances by propensity score. At a median follow-up of 22 months (mo), median unadjusted OS was not reached (NR) in NAVIGATOR versus (vs) 26.4 mo in Study 1002; OS rate at 6 and 24 mo was 100% and 75% in NAVIGATOR vs 84% and 63% in Study 1002 (K–M curve comparison: P=0.0085). Inverse probability weighted-adjusted analysis showed median OS was NR in NAVIGATOR and 12.6 mo in Study 1002; OS rate at 6 and 24 mo was 100% and 77% in NAVIGATOR vs 56% and 38% in Study 1002, respectively (K–M curve comparison: P=0.0001). Median (unadjusted and adjusted) PFS was NR in NAVIGATOR and 3.4 mo in Study 1002. Unadjusted/adjusted PFS rates at 6 and 24 mo were 92%/93% and 77%/71% in NAVIGATOR vs 14%/9% and 7%/6% in Study 1002 (K–M curve comparison: P=0.0000).
Conclusions
Although our sample size was small, AVA demonstrated significantly more durable survival outcomes compared with other TKIs used to treat pts with U/M PDGFRA D842V-mutant GIST.
Clinical trial identification
NCT02508532.
Editorial acknowledgement
Medical writing support was provided by Manoshi Nath, and editorial support was provided by Sinead Stewart, all of Paragon, Knutsford, UK, supported by Blueprint Medicines Corporation, Cambridge, MA according to Good Publication Practice guidelines.
Legal entity responsible for the study
Blueprint Medicines Corporation.
Funding
Blueprint Medicines Corporation.
Disclosure
M. von Mehren: Non-remunerated activity/ies: Blueprint Medicines Corporation; Non-remunerated activity/ies: Arog Pharmaceuticals; Non-remunerated activity/ies: Deciphera Pharmaceuticals. M. Heinrich: Honoraria (self): Blueprint Medicines Corporation; Honoraria (self): MolecularMD; Honoraria (self): Novartis; Honoraria (self): Deciphera Pharmaceuticals. H. Shi, S. Dimitrijević, G. Hoehn, S. Chiroli: Shareholder/Stockholder/Stock options, Full/Part-time employment: Blueprint Medicines Corporation. S. Iannazzo: Advisory/Consultancy: Blueprint Medicines Corporation. R. Mankoski: Full/Part-time employment: Blueprint Medicines Corporation. S. George: Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicines Corporation; Advisory/Consultancy, Research grant/Funding (institution): Deciphera Pharmaceuticals; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Ariad; Research grant/Funding (institution): Novartis; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: AstraZeneca.