Clinical efficacy comparison of avapritinib with other tyrosine kinase inhibitors in gastrointestinal stromal tumors with PDGFRA D842V mutation: a retrospective analysis of clinical trial and real-world data

BMC Cancer. 2021 Mar 19;21(1):291. doi: 10.1186/s12885-021-08013-1.


Background: Avapritinib, a potent inhibitor of KIT and platelet-derived growth factor receptor A (PDGFRA) tyrosine kinases, has demonstrated unprecedented clinical activity in PDGFRA D842V-mutant gastrointestinal stromal tumors (GIST).

Methods: This retrospective analysis compared efficacy of avapritinib in patients enrolled in the NAVIGATOR phase 1 trial (NCT02508532) with the efficacy of other tyrosine kinase inhibitors (TKIs) in patients with unresectable/metastatic PDGFRA D842V-mutant GIST enrolled in a retrospective natural history study (Study 1002). The primary endpoint was overall survival (OS) from the start of reference treatment (avapritinib for NAVIGATOR patients or first-line TKI for treatment of unresectable/metastatic GIST for Study 1002 patients); the secondary endpoint was progression-free survival (PFS). Adjusted Kaplan-Meier survival curves were compared by Cox regression.

Results: Fifty-six (NAVIGATOR) and 19 (Study 1002) patients with PDGFRA D842V-mutant GIST were evaluated; of the 56 patients from NAVIGATOR, a subgroup of patients treated with either 300 mg (recommended phase 2 dose) or 400 mg (maximum tolerated dose) avapritinib starting dose (n = 38) were analyzed separately. Patient characteristics were adjusted for imbalances by propensity score between the study groups. Inverse probability of treatment weighting-adjusted Kaplan-Meier analysis of OS showed median OS was not reached for NAVIGATOR patients treated with any of the avapritinib doses tested and was 12.6 months for Study 1002 patients; OS rate at 6/48 months was 100%/63% in NAVIGATOR and 56%/17% in Study 1002 (P = 0.0001). In the 300/400 mg subgroup, adjusted OS rates at 6/36 months were 100%/73 and 68%/20% in Study 1002 (P = 0.0016). Adjusted median PFS was 29.5 months in NAVIGATOR and 3.4 months in Study 1002.

Conclusions: In this indirect, retrospective analysis, avapritinib demonstrated more durable survival outcomes compared with other TKIs in patients with unresectable/metastatic PDGFRA D842V-mutant GIST.

Trial registration: The NAVIGATOR trial was registered at as per July 2015, Identifier: NCT02508532 .

Keywords: Avapritinib; GIST; PDGFRA D842V mutation.

Publication types

  • Comparative Study

MeSH terms

  • Clinical Trials, Phase I as Topic
  • Female
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / mortality
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Retrospective Studies
  • Triazines / administration & dosage*
  • Triazines / adverse effects


  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrroles
  • Triazines
  • avapritinib
  • Receptor, Platelet-Derived Growth Factor alpha

Associated data