biostudies-literatureGross AMCCR NIH HHSIntramural NIH HHSU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)NCI NIH HHS105-115https://www.ebi.ac.uk/biostudies/studies/S-EPMC12423960biostudies-literatureUnknown31(1)The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies. The objective response rate was 63.6% (21/33 participants). Median maximal PN volume decrease was 23.6% (range: -48.1% to 5.5%). No disease progression relative to baseline PN volumes occurred before data cutoff, with a median of 28 cycles completed (range: 1-78, 28 d per cycle). Participants experienced decreased tumor pain intensity and pain interference. Adverse events (AEs) were similar to those of the pediatric trial; acneiform rash was the most prevalent AE. Phosphorylation ratios of ERK1/2 decreased significantly (ERK1 median change: -64.6% (range: -99.5% to 90.7%), ERK2 median change: -57.3% (range: -99.9% to 84.4%)) in paired PN biopsies (P ≤ 0.001 for both isoforms) without compensatory phosphorylation of AKT1/2/3. The sustained PN volume decreases, associated improvement in pain and manageable AE profile indicate that selumetinib provides benefit to adults with NF1 and inoperable PNs. ClinicalTrials.gov identifier: NCT02407405 .Nature medicineSelumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.PMC12423960U54 CA196519HHSN261200800001E5U54CA196519-05HHSN261200800001CZ01 SC010354Widemann BCSrivastava AKGross AMSankaran HFang FClapp DWGovindharajulu JPShern JFRubinstein LVDixon SAHTibery CFagan MDavis CHerrick WGTamula MARhodes SDChen APMartin SJohnson BCAngus SPBrowne ATReid OKaplan RNDombi EXuei XDoroshow JHZhang XFoster JCOng MJParchment REBaldwin AOn TJHeisey KWolters PLO'Sullivan Coyne GfalseSelumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.The MEK inhibitor selumetinib induces objective responses and provides clinical benefit in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PNs). To evaluate whether similar outcomes were possible in adult patients, in whom PN growth is generally slower than in pediatric patients, we conducted an open-label phase 2 study of selumetinib in adults with NF1 PNs. The study was designed to evaluate objective response rate (primary objective), tumor volumetric responses, patient-reported outcomes and pharmacodynamic effects in PN biopsies. The objective response rate was 63.6% (21/33 participants). Median maximal PN volume decrease was 23.6% (range: -48.1% to 5.5%). No disease progression relative to baseline PN volumes occurred before data cutoff, with a median of 28 cycles completed (range: 1-78, 28 d per cycle). Participants experienced decreased tumor pain intensity and pain interference. Adverse events (AEs) were similar to those of the pediatric trial; acneiform rash was the most prevalent AE. Phosphorylation ratios of ERK1/2 decreased significantly (ERK1 median change: -64.6% (range: -99.5% to 90.7%), ERK2 median change: -57.3% (range: -99.9% to 84.4%)) in paired PN biopsies (P ≤ 0.001 for both isoforms) without compensatory phosphorylation of AKT1/2/3. The sustained PN volume decreases, associated improvement in pain and manageable AE profile indicate that selumetinib provides benefit to adults with NF1 and inoperable PNs. ClinicalTrials.gov identifier: NCT02407405 .2025-01-01T00:00:00Z2025 Jan2026-06-03T02:28:44.379Z2026-04-23T03:10:02.219ZS-EPMC124239603976242110.1038/s41591-024-03361-4