Lgg-05. Report on Pediatric Brain Tumor Consortium (pbtc)-029b, a Prospective Phase 2 Clinical Trial of Selumetinib in Treating Young Patients With Recurrent/progressive Low-grade Glioma: New Results on Strata 2, 5, and 6 With Updated Long-term Survival Outcomes on Strata 1, 3, and 4
Year: 2024
Type: conference-abstract
Abstract: BACKGROUND PBTC-029B was a phase 2 trial evaluating efficacy of selumetinib (up to 26 courses) in children with recurrent/progressive low-grade glioma. We report new results on strata 2, 5, and 6 as well as update long-term survival outcomes on strata 1, 3, and 4. METHODS Stratum 2 enrolled children with pilocytic astrocytoma (PA) whose tumor screened negative for the BRAF-KIAA1549 fusion and the BRAFV600E mutation. Stratum 5 enrolled children with non-PA whose tumor screened positive for one of these two BRAF aberrations. Stratum 6 enrolled children who consented to tissue screening, but there was an assay failure. Responses were based on T2/FLAIR. RESULTS Stratum 2: among 14 patients, there was 1 partial response (PR), 7 stable disease (SD) and 6 progressive disease (PD) with overall response rate (ORR) of 7.1%. Two-year progression-free survival (PFS)/overall survival (OS) were 57.1/100%, respectively. Stratum 5: among 23 patients, there was 1 complete response, 4 PR, 12 SD and 6 PD with ORR of 21.7%. Two-year PFS/OS were 74.8%/100%, respectively. Stratum 6: among 26 patients, there were 7 PR, 14 SD and 5 PD with ORR of 26.9%. Two-year PFS/OS were 72.0%/100%, respectively. Long-term outcomes have now been evaluated in strata 1, 3, and 4. Stratum 1 enrolled patients with PA whose tumor screened positive for one of the two BRAF aberrations; stratum 3 enrolled patients with neurofibromatosis type-1 (NF1) associated pLGG; and stratum 4 enrolled non-NF1 optic pathway/hypothalamic tumors. Among strata 1, 3, and 4, the current median follow-up for patients without events are 60.4, 60.4, and 58.1 months, respectively. Five-year PFS/OS are 30.8%/88.9%, 54.2%/100%, and 51.0%/100%, respectively. CONCLUSIONS These data demonstrate that selumetinib provides tumor stability and responses among diverse pLGG tumors as well as show that many patients will achieve long-term disease control even several years after stopping treatment.
Source: Neuro-Oncology
Authors: Jason Fangusaro, Arzu Onar-Thomas, Tina Young Poussaint, Shelly Lensing, Azra H Ligon, Neal Lindeman, Anuradha Banerjee, Lindsay Kilburn, Alicia Lenzen, Natasha Pillay-Smiley, Ian F Pollack, Nathan Robison, Sonia Partap, Ibrahim Qaddoumi, Daniel Landi, David T W Jones, Clinton F Stewart, Maryam Fouladi, Ira J Dunkel
Institutions: Emory University, Children's Healthcare of Atlanta, St. Jude Children's Research Hospital, Boston Children's Hospital, Harvard University, Brigham and Women's Hospital, Weill Cornell Medicine, University of California, San Francisco, UCSF Benioff Children's Hospital, Children's National, Lurie Children's Hospital, Cincinnati Children's Hospital Medical Center, University of Pittsburgh, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Children's Hospital of Los Angeles, Stanford University, German Cancer Research Center, Hopp Children's Cancer Center Heidelberg, Nationwide Children's Hospital, Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,389
OpenAlex ID: W4399785271