NFM-07. SPRINT: PHASE II STUDY OF THE MEK 1/2 INHIBITOR SELUMETINIB (AZD6244, ARRY-142886) IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1 (NF1) AND INOPERABLE PLEXIFORM NEUROFIBROMAS (PN). Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Gross, Andrea; Wolters, Pamela; Baldwin, Andrea; Dombi, Eva; Fisher, Michael J; Weiss, Brian; Kim, AeRang; Blakeley, Jaishri; Whitcomb, Patricia; Holmblad, Marielle; Maritin, Staci; Roderick, Marie Claire; Paul, Scott M; Therrien, Janet; Heisey, Kara; Doyle, Austin; Smith, Malcolm; Glod, John; Steinberg, Seth; Widemann, Brigitte C
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i143
• Page End: i144
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.515
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: PN in NF1 cause substantial morbidity. In a phase I trial of selumetinib, 17/24 patients had a partial response (PR). This study evaluates the PR rate of PN to selumetinib and changes in PN-related morbidities. Patients 2-18 years with NF1, inoperable PN and ≥ 1 PN-related morbidity received continuous 28-day cycles of selumetinib (25 mg/m 2 PO BID). Response (volumetric MRI analysis; PR = PN volume decrease ≥20%) and PN-related morbidities were assessed after every 4 cycles. Fifty children (30 male, median age 10.2 years, range 3.5, 17.4) enrolled. Disfigurement (n=44), motor dysfunction (n=33) and pain (n=28) were the most frequent PN-related morbidities. As of November 5, 2017: median cycle number 19.5 (range 0, 29); median change in PN volume -27.7% (range -50.6%, 2.2%). Best response PR (36 patients, 72%), stable disease (12 patients, 24%); 2 (4%) had no re-staging evaluations. Of the 36 PR, 32 were confirmed on ≥ two consecutive restaging studies. Pain intensity and interference scores improved significantly (p <0.01) over one year, as did strength (0-5 scale) and range of motion (degrees) (p < 0.01). Most frequent toxicities: gastrointestinal, asymptomatic creatine kinase increase, acneiform rash and paronychia. Selumetinib dose was reduced in 12 patients, of which 5 were removed from treatment. The response rate from this study (72%) confirms our previously observed rate (71%). Most responses have lasted ≥6 months. Improvements in PN-related pain and motor impairment demonstrate that selumetinib can provide clinical benefit. Data validation and further analyses are ongoing.