2018 ASCO Annual Meeting!
Session: Pediatric Oncology I
Type: Oral Abstract Session
Time: Saturday June 2, 3:00 PM to 6:00 PM
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).
Pediatric Solid Tumors
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 10503)
Author(s): Andrea M. Gross, Pamela Wolters, Andrea Baldwin, Eva Dombi, Michael J. Fisher, Brian D. Weiss, AeRang Kim, Jaishri O'Neill Blakeley, Patricia Whitcomb, Marielle Holmblad, Staci Martin, Marie Claire Roderick, Scott M. Paul, Janet Therrien, Kara Heisey, Austin Doyle, Malcolm A. Smith, John Glod, Seth M. Steinberg, Brigitte C. Widemann; National Institutes of Health, Bethesda, MD; National Cancer Institute, Bethesda, MD; Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD; Children's Hosp of Philadelphia, Philadelphia, PA; Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Children's National Health System, Washington, DC; Johns Hopkins University School of Medicine, Baltimore, MD; Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI, Frederick, MD; Pediatric Oncology Branch, NCI, Bethesda, MD; Pediatric Oncology Branch, National Institutes of Health, Bethesda, MD; Rehabilitation Medicine Deparment, Clinical Center, NCI, Bethesda, MD; Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc, Frederick, MD; National Cancer Institute, Rockville, MD; Cancer Therapy Evaluation Program, National Cancer Institute, Washington, DC; National Cancer Institute at the National Institutes of Health, Bethesda, MD; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Background: PN in NF1 can cause substantial morbidity, and there are no approved medical therapies. In a phase I trial of selumetinib, 17/24 (71%) patients (pts) had a partial response (PR)(Dombi, et al. N Engl J Med 2016; 375:2550-2560). This open-label phase II study (NCT01362803) determines the PR rate of PN treated with selumetinib and changes in PN related morbidities. Methods: Patients 2-18 years old with NF1, inoperable PN and ≥ 1 PN related morbidity received selumetinib at the recommended phase II dose (25 mg/m2 PO BID) with continuous dosing (1 cycle = 28 days). Response was evaluated with volumetric MRI analysis (PR = target PN volume decrease ≥20%) and PN related morbidities (pain, disfigurement, functional morbidities) assessed with standardized evaluations after every 4 cycles. Results: 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) with 38 pts remaining on treatment; median change in PN volume from baseline -27.7% (range -50.6%, 2.2%); best response PR (36 pts, 72%), stable disease (12 pts, 24%); 2 subjects (4%) had no re-staging. Of the 36 total PR, 32 were confirmed on ≥ two consecutive restaging scans and 22 continue to have a PR ≥ 1 year after it was first achieved. Between baseline and end of year 1 evaluations, parent and child-reported pain intensity and pain interference scores significantly improved (p <0.01), as did strength (0-5 scale) and range of motion (degrees) of affected muscle groups/joints (p < 0.01). The most frequent toxicities were nausea/vomiting, diarrhea, asymptomatic creatine kinase increase, acneiform rash and paronychia. Selumetinib dose was reduced in 12 pts, of which 5 were removed from treatment. Conclusions: The response rate from this study (72%) confirms our previously observed response rate (71%). Most responses were sustained ≥6 months. Improvements in PN related pain and motor impairment demonstrate that selumetinib can provide clinical benefit. Data validation and further analyses are ongoing. Clinical trial information: NCT01362803