Major Research Findings

Avapritinib is a new tyrosine kinase inhibitor that has shown promise in the treatment of gastrointestinal stromal tumors (GIST) and advanced systemic mastocytosis (AdvSM). 9 A case report showed that avapritinib was effective in treating GIST with a PDGFRA D842V mutation, a common type of GIST that often becomes resistant to other treatments. 25 A phase III study VOYAGER compared avapritinib to regorafenib, another GIST treatment, and found that avapritinib was more effective. 14 A phase I/II study NAVIGATOR evaluated the safety and efficacy of avapritinib in patients with GIST in China and found that it was both safe and effective. 22 Avapritinib has also been shown to be effective in the treatment of AdvSM, a rare blood cancer caused by a mutation in the KIT gene. 23 In a phase I trial EXPLORER, avapritinib showed a high response rate and was well tolerated in patients with AdvSM. 22 A phase II trial PATHFINDER further confirmed the efficacy and safety of avapritinib in treating AdvSM, leading to a high rate of clinical, morphological, and molecular responses. 23 The study also proposed refined response criteria for AdvSM. 19 The use of avapritinib in a compassionate use program for patients with AdvSM has shown that it can be effective in treating patients who have failed previous treatments and may be a good bridging therapy before bone marrow transplantation. 6 Preclinical studies have further demonstrated that avapritinib is effective in inhibiting the growth and survival of mast cells in patients with systemic mastocytosis. 10 Moreover, avapritinib, when used in combination with CDK4/CDK6 inhibitors, has been shown to enhance the inhibition of mast cell growth. 17

Benefits and Risks

Benefit Summary

Avapritinib has shown promise in treating patients with GIST with a PDGFRA D842V mutation, a common type of GIST that often becomes resistant to other treatments. 9 It has also been shown to be effective in treating patients with AdvSM, a rare blood cancer caused by a mutation in the KIT gene. 22 , 23 Avapritinib has also been shown to be a good bridging therapy before bone marrow transplantation in patients with AdvSM who have failed previous treatments. 6 Avapritinib has been shown to inhibit the growth and survival of mast cells in patients with systemic mastocytosis. 10 Furthermore, avapritinib, when used in combination with CDK4/CDK6 inhibitors, has been shown to enhance the inhibition of mast cell growth. 17

Risk Summary

Avapritinib has been associated with some potential side effects, including preseptal cellulitis, intraocular inflammatory reaction, persistent corneal epithelial defect, and severe parkinsonism. 4 , 13

Comparison Between Studies

Commonalities Between Studies

Many studies have shown that avapritinib is effective in treating patients with GIST with a PDGFRA D842V mutation and patients with AdvSM. 9 , 25 , 22 , 23 , 6 , 10 , 17 Several studies have found that avapritinib is generally well tolerated by patients. 22 , 23

Differences Between Studies

There are some differences in the results of studies regarding the efficacy and safety of avapritinib. 9 , 25 , 22 , 23 , 6 , 10 , 17 For example, one study reported a patient who experienced preseptal cellulitis, intraocular inflammatory reaction, and persistent corneal epithelial defect after treatment with avapritinib. 4 Another study reported a patient who experienced severe parkinsonism after receiving avapritinib. 13 However, other studies did not report these side effects. 22 , 23

Consistency and Contradictions in the Results

Many studies have shown that avapritinib is effective in treating GIST with a PDGFRA D842V mutation and patients with AdvSM. 9 , 25 , 22 , 23 , 6 , 10 , 17 However, there are some contradictions in the results regarding the side effects of avapritinib. 4 , 13 Further research is needed to resolve these contradictions.

Notes on Real-world Applications

Avapritinib is a promising new treatment for patients with GIST with a PDGFRA D842V mutation and patients with AdvSM. 9 , 25 , 22 , 23 , 6 , 10 , 17 However, it is important to be aware of the potential side effects associated with avapritinib, including preseptal cellulitis, intraocular inflammatory reaction, persistent corneal epithelial defect, and severe parkinsonism. 4 , 13 This information should be carefully considered by patients and their doctors when deciding whether or not to use avapritinib.

Limitations of Current Research

Research on avapritinib is still in its early stages and the available data on its efficacy and safety are limited. 9 , 25 , 22 , 23 , 6 , 10 , 17 , 13 , 4 Furthermore, there is a lack of research on the side effects of avapritinib. 4 , 12 Further research is needed to better understand the efficacy and safety of avapritinib.

Future Research Directions

Further large-scale clinical trials are needed to gain a better understanding of the efficacy and safety of avapritinib. 9 , 25 , 22 , 23 , 6 , 10 , 17 , 13 , 4 Additionally, more research is needed on the side effects of avapritinib. 4 , 12 These studies will help clarify the indications and precautions for using avapritinib.

Conclusion

Avapritinib is a promising new tyrosine kinase inhibitor that may be effective in treating patients with GIST with a PDGFRA D842V mutation and patients with AdvSM. 9 , 25 , 22 , 23 , 6 , 10 , 17 However, it is important to be aware of the potential side effects associated with avapritinib, including preseptal cellulitis, intraocular inflammatory reaction, persistent corneal epithelial defect, and severe parkinsonism. 4 , 13 More research is needed to better understand the efficacy and safety of avapritinib, which will ultimately help doctors and patients make more informed decisions about the use of this drug. 12