KEY TAKEAWAYS
- The Phase 2 study assessed avapritinib in AdvSM pts in a two-year follow-up.
- The primary endpoint was ORR per mIWG response criteria. Secondary endpoints included TTR, DOR, PFS, OS, mean change from baseline objective disease burden measures, and safety.
- Avapritinib demonstrated strong efficacy and manageable safety, irrespective of previous treatments or disease subtypes.
AdvSM is a mast cell (MC) disorder fueled by the KIT D816V mutation. Avapritinib is approved for use in adults with AdvSM in the USA and Europe who have undergone at least one previous treatment. This report shared findings from the PATHFINDER study, with a two-year follow-up period.
The primary endpoint was the overall response rate (ORR) based on the modified International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (mIWG) response criteria. Secondary endpoints included the time to response (TTR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Additionally, changes from baseline in objective measures of disease burden were examined, such as bone marrow MC load, serum tryptase levels, blood KIT D816V variant allele fraction (VAF), spleen volume, and safety parameters.
As of September 9, 2022, 107 patients (pts) with confirmed AdvSM started on avapritinib daily dosages, with the majority (n=105) on a 200 mg dose and two on a 100 mg dose. Among the 83 pts evaluated based on mIWG response criteria, the overall response rate (ORR) stood at 73%, with a confidence interval of 95% ranging from 63-83%. Additionally, 27% achieved complete remission (CR) or CR with partial hematologic recovery. For those who were treatment-naive (n=27/30), the ORR was remarkably high at 90%, and 40% achieved CR or CRh. The median time to response was 2.3 months, but the median values for DOR, PFS, and OS have not yet been determined.
The treatment showed benefits across different prior therapy experiences and subtypes. Significant reductions were observed in markers of disease burden, such as bone marrow mast cell burden (88%), serum tryptase levels (92%), KIT D816V VAF (81%), and spleen volume (70% showed a reduction of at least 35%). Treatment-related adverse events (TRAEs) occurred but were generally manageable, and no treatment-related deaths were reported.
Avapritinib demonstrated strong efficacy and a good benefit-risk balance, irrespective of previous treatments or specific disease subtypes.
Source: https://clml-soho2023.elsevierdigitaledition.com/388/index.html
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03580655
Gotlib, J., Reiter, A., Radia, D.H., Deininger, M.W., George, T.I., Panse, J., Vannucchi, A.M., Platzbecker, U., Alvarez-Twose, I., Mital, A., Hermine, O., Dybedal, I., Hexner, E.O., Span, L., Mesa, R., Bose, P., Pettit, K.M., Oh, S.T., Lin, H-M., Dimitrijević, S., Muñoz-González, J.I., DeAngelo, D.J. Avapritinib in Patients With Advanced Systemic Mastocytosis (AdvSM): Efficacy and Safety Analyses from the Phase 2 PATHFINDER Study With 2‑Year Follow‑Up.
