Objective: This research aimed to compare the relative efficacy of avapritinib versus midostaurin for patients with advanced systemic mastocytosis. Method: A systematic literature review was performed to identify relevant evidence. Unanchored matching-adjusted indirect comparisons were conducted for overall survival (OS), overall response rate (ORR) and complete remission (CR). Results: The systematic literature review identified the clinical trials EXPLORER and PATHFINDER (investigating avapritinib) and D2201 and A2213 (investigating midostaurin). The avapritinib versus midostaurin adjusted hazard ratio for OS was 0.44 (95% CI: 0.25–0.76), and the adjusted odds ratios for ORR and CR were 4.06 (95% CI: 3.09–5.33) and 9.56 (95% CI: 0.97–93.81), respectively. Conclusion: The results suggest that avapritinib improves survival and response (ORR and CR) compared with midostaurin.

Plain language summary

Systemic mastocytosis is a rare blood disorder caused by the build-up of too many abnormal mast cells, a type of white blood cell, in the skin and organs. Patients with advanced systemic mastocytosis have a low life expectancy and limited treatment options. This research aimed to compare the effectiveness of two recent and innovative treatments (called avapritinib and midostaurin) in extending life expectancy and decreasing mast cells and organ damage. As avapritinib and midostaurin were not investigated in the same clinical studies, it was necessary to compare the two treatments using the results from studies of each individual treatment. The published evidence used to support this comparison was systematically searched for and consisted of four clinical studies: the EXPLORER and PATHFINDER studies (investigating avapritinib) and D2201 and A2213 studies (investigating midostaurin). An indirect comparison between the studies was made that adjusted for differences in key patient characteristics. The results suggest that compared with midostaurin, avapritinib has the potential to extend life expectancy and decrease disease burden.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 18, No. 13

Supplemental Materials

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Received 24 November 2021

Accepted 19 January 2022

Published online 4 February 2022

Published in print April 2022

Information

Keywords

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2021-1509

Author contributions

All authors were involved in the conception and design of this work, contributed to the analysis or interpretation of data, contributed to drafting or revising it critically for important intellectual content and approved the final version.

Acknowledgments

The development of the systematic literature review used for this work was led by M Kaur, BresMed Health Solutions. The authors would also like to acknowledge editorial and medical writing support was provided by N Beavers and M Woods, BresMed Health Solutions.

Financial & competing interests disclosure

This work was sponsored by Blueprint Medicines. S Iannazzo is an employee of Blueprint Medicines. H Pilkington, S Smith and N Roskell are employees of BresMed. BresMed received consultancy fees from Blueprint Medicines for the development of this work. The authors did not receive direct payment because of this work outside of their normal salary payments. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Editorial and medical writing support was provided by N Beavers and M Woods, BresMed Health Solutions. Medical writing support was funded by Blueprint Medicines.

Data sharing statement

The authors certify that this manuscript reports the secondary analysis of clinical trial data that have been shared with them, and that the use of these shared data is in accordance with the terms (if any) agreed upon their receipt. The source of these data is: EXPLORER (NCT02561988) and PATHFINDER (NCT03580655).

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