Abstract
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 ClinicalTrials.gov as per July 2015, Identifier: NCT02508532.
Original language | English |
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Article number | 291 |
Pages (from-to) | 291 |
Journal | BMC Cancer |
Volume | 21 |
Issue number | 1 |
DOIs | |
State | Published - Feb 19 2021 |
Keywords
- Clinical Trials, Phase I as Topic
- Female
- Gastrointestinal Stromal Tumors/drug therapy
- Humans
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Progression-Free Survival
- Protein Kinase Inhibitors/administration & dosage
- Pyrazoles/administration & dosage
- Pyrroles/administration & dosage
- Receptor, Platelet-Derived Growth Factor alpha/antagonists & inhibitors
- Retrospective Studies
- Triazines/administration & dosage
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Fox Chase Cancer Center: Avapritinib Provided Greater Benefit Than Other Tyrosine Kinase Inhibitors for Mutated Gastrointestinal Stromal Tumors
05/18/21 → 05/19/21
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