Best of ASCO - 2014 Annual Meeting



Complete radiographic responses in pediatric patients with BRAFV600-positive tumors including high-grade gliomas: Preliminary results of an ongoing phase 1/2a safety and pharmacokinetics (PK) study of dabrafenib.

Pediatric Solid Tumors

Pediatric Oncology

2014 ASCO Annual Meeting

Abstract No:

J Clin Oncol 32:5s, 2014 (suppl; abstr 10056)

Attend this session at the
2014 ASCO Annual Meeting!

Session: Pediatric Oncology

Type: General Poster Session

Time: Monday June 2, 8:00 AM to 11:45 AM

Location: S Hall A2

Personalize your Meeting experience with a suggested or customized itinerary!

Author(s): Mark W. Kieran, Kenneth J. Cohen, Francois Doz, Ira J. Dunkel, Darren R Hargrave, Trent Ryan Hummel, Irene Jimenez, Sarah Leary, Andrew DJ Pearson, Christine A. Pratilas, James Whitlock, Michael Durante, Diana M. Gibson, Patricia Haney, Mark W. Russo, Benjamin B. Suttle, Birgit Geoerger; Dana-Farber Cancer Institute, Boston, MA; The Johns Hopkins University School of Medicine, Baltimore, MD; Institut Curie, Paris, France; Memorial Sloan-Kettering Cancer Center, New York, NY; Great Ormond Street Hospital, London, United Kingdom; Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Seattle Children's, Seattle, WA; Institute of Cancer Research, Sutton, United Kingdom; The Hospital for Sick Children, Toronto, ON, Canada; GlaxoSmithKline, Collegeville, PA; GlaxoSmithKline, Philadelphia, PA; GlaxoSmithKline, RTP, NC; Institut Gustave Roussy, Villejuif, France

Abstract Disclosures


Background: Dabrafenib is a selective inhibitor of V600 mutant BRAF kinase activity with a mechanism of action consistent with adenosine triphosphate-competitive inhibition. Dabrafenib has demonstrated anti-tumor efficacy in adult patients (pts) with BRAFV600 mutant tumors, including melanoma, papillary thyroid cancer (PTC), and non-small cell lung cancer. Methods: This 2-part study was designed to identify phase 2 recommended dose, safety, PK, and clinical activity in pediatric pts who have had ≥1 previous therapy. Part 1 is a PK-driven dose escalation. Part 2 is an expansion study to evaluate the safety and activity of dabrafenib in pediatric pts with 1 of 4 pre-specified tumor types. Pts are treated with dabrafenib orally twice daily, using capsules or a powder for oral suspension. Serial PK samples are obtained on days 1 and 15. Imaging is performed every 2 cycles, and responses require confirmation on a follow-up scan at least 4 weeks later. Results: From May 2013 to Jan 2014, 8 pts (median age, 11 y; range 3-17 y) with recurrent/refractory BRAFV600 mutant solid tumors including 6 high grade glioma (HGG), 1 each of Langerhans cell histiocytosis (LCH), and PTC were enrolled at dose levels 3mg/kg (n=3) and 3.75mg/kg (n=5). Radiographic responses for the HGG pts included 3 complete responses (2 confirmed and maintained at the 6 month assessment [both anaplastic astrocytoma], 1 unconfirmed [pleomorphic xanthoastrocytoma]), and 2 progressive disease. The LCH pt continues to exhibit stable disease at week 16. Data are not yet available for a PTC pt and 1 HGG pt. There were no DLTs or drug-related grade 3/4 toxicities in these 8 pts. No dose reductions have been required, and PK data analysis and dose escalation continues. Two pts (1 in each cohort) achieved plasma dabrafenib concentrations associated with clinical efficacy in adults. Conclusions: Dabrafenib shows encouraging initial clinical activity in this small number of evaluable pediatric pts with BRAFV600 mutant solid tumors, including primary brain tumors. The preliminary safety profile in pediatric pts is consistent with that in adults. Clinical trial information: NCT01677741.


  Other Abstracts in this Sub-Category:


1. Real-time central review: A report of the first 3,000 patients enrolled on the Children’s Oncology Group Renal Tumor Biology and Risk Stratification protocol AREN03B2.

Meeting: 2014 ASCO Annual Meeting Abstract No: 10000 First Author: Elizabeth Anne Mullen
Category: Pediatric Oncology - Pediatric Solid Tumors


2. Treatment of stage IV favorable histology Wilms tumor with incomplete lung metastasis response after chemotherapy: A report from Children’s Oncology Group study AREN0533.

Meeting: 2014 ASCO Annual Meeting Abstract No: 10001 First Author: David B. Dix
Category: Pediatric Oncology - Pediatric Solid Tumors


3. Outcome of localized blastemal-type nephroblastoma patients treated according to intensified treatment in the SIOP 2001 protocol: A report of the SIOP-RTSG.

Meeting: 2014 ASCO Annual Meeting Abstract No: 10002 First Author: Marry M van den Heuvel-Eibrink
Category: Pediatric Oncology - Pediatric Solid Tumors