Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum.
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Ошибки и ограничения
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Parker Victoria E R, Keppler-Noreuil Kim M, Faivre Laurence, Luu Maxime, Oden Neal L, De Silva Leena, Sapp Julie C, Andrews Katrina, Bardou Marc, Chen Kong Y, Darling Thomas N, Gautier Elodie, Goldspiel Barry R, Hadj-Rabia Smail, Harris Julie, Kounidas Georgios, Kumar Parag, Lindhurst Marjorie J, Loffroy Romaric, Martin Ludovic, Phan Alice, Rother Kristina I, Widemann Brigitte C, Wolters Pamela L, Coubes Christine, Pinson Lucile, Willems Marjolaine, Vincent-Delorme Catherine, PROMISE Working Group, Vabres Pierre, Semple Robert K, Biesecker Leslie G
Аннотация
METHODS: Thirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy.
RESULTS: Thirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of -7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently.
CONCLUSION: This study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk-benefit evaluations for sirolimus treatment in PROS.