Background. Neurofibromatosis type 1 is an autosomal dominant disease caused by the defect of the antitumoral gene NF1 that normally downregulates the RAS/RAF/MEK/ERK pathway. Neurofibromas can lead to severe morbidity. The only etiological treatment approved for inoperable plexiform neurofibromas is selumetinib, a MEK1/2 inhibitor suppressing growth signalling downstream of RAS. Selumetinib was initially approved for melanoma and small-cell lung cancer at a higher dose. Since at those dosages and settings reduction in pulmonary function and lung fibrosis have been reported, patients with NF1 treated with selumetinib undergo spirometry quarterly.

Methods. We collected FVC and FEV1 before selumetinib initiation and quarterly for 2 years in all consecutive patients currently receiving selumetinib at our Institute. We used the ANOVA test to compare FVC registered at each appointment and similarly for FEV1. We used the Student test to compare pre-selumetinib FVC and FEV1 with 1-year values and pre-selumetinib with 2 years. The alpha error was considered 0.05.

Results. We identified 22 patients, age 11 years (SD 4), 15 males. Before selumetinib start mean FVC was 101% (SD 16), FEV1 103% (SD 20), one year after FVC was 94% (SD 17), FEV1 100% (SD 20), two years after FVC was 100% (SD 16), FEV1 102% (15). Anova test reported p=0.67. Student tests reported non-significative differences.

Conclusions. Our experience suggests that, in children and young adults with neurofibromatosis 1, selumetinib does not impact pulmonary function even in the long term, therefore periodic pulmonary function testing could be considered not necessary during follow-up.