Precision Therapy for Brain Cancer Shows Promise in Some Patients
Primary brain tumors are diagnosed in approximately 100,000 people annually in the United States, and glioblastomas are the most common and aggressive type. Patients diagnosed with glioblastoma have an average survival of less than two years despite standard of care combination therapy, and new therapeutic approaches are needed.
A new study, led by Andrew B. Lassman, MD, FAAN, chief of the neuro-oncology division in the Department of Neurology, associate director for clinical trials at Columbia’s Herbert Irving Comprehensive Cancer Center (HICCC), and associate dean of clinical trials at the Vagelos College of Physicians and Surgeons, addresses the safety and efficacy of infigratinib, a fibroblast growth factor receptor (FGFR)-tyrosine kinase inhibitor, for patients with recurrent glioblastomas and related tumors.
Infigratinib is a novel drug that inhibits mutated versions of FGFR1–3 and was developed to treat FGFR-driven cancers and other conditions. The results of the international phase II clinical trial, published in Clinical Cancer Research, demonstrate that FGFR targeted therapy with infigratinib had limited efficacy in patients with recurrent gliomas and a wide range of different FGFR genetic alterations. However, activating point mutations in FGFR1 or FGFR3 or FGFR3-TACC3 fusion in tumor tissue, present in a subset of patients, predicted durable disease control from treatment with infigratinib.
“Our findings are particularly encouraging in a setting where there are limited therapeutic options,” says Dr. Lassman, a member of the HICCC’s Precision Oncology and Systems Biology research program. “The study also underscores the importance of precision medicine in the approach to cancer generally, and brain tumors in particular: FGFR inhibition had limited to no efficacy in patients with recurrent gliomas harboring any FGFR alteration, but durable disease control was apparent in cases with specific FGFR point mutations or gene fusions. Further studies of FGFR inhibitors with refined biomarker inclusion criteria are warranted.”
The study builds on the discoveries (and references therein) made by Drs. Antonio Iavarone and Anna Lasorella at Columbia University Irving Medical Center (CUIMC) that fibroblast growth factor receptor (FGFR) gene fusions drive growth in a subset of gliomas. The trial was conducted at the Herbert Irving Comprehensive Cancer Center in partnership with the William Rhodes and Louise Tilzer-Rhodes Center for Glioblastoma at New York-Presbyterian Hospital, and 13 other centers in the U.S., Spain, Switzerland, the Netherlands and Belgium. In next steps, Drs. Lassman and colleagues are designing a subsequent trial of infigratinib for patients with newly diagnosed gliomas harboring the rare activating FGFR point mutations or FGFR3 fusions that were predictive of benefit in this trial.
“Our long-term aim is to identify treatments that are robustly effective for different subpopulations of glioma,” says Dr. Lassman, “each of which may require a different therapy, instead of our current approach, which is ‘one size fits all’, or more accurately, ‘no size fits anyone’.”
The paper, “Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study”, published on March 28, 2022, in Clinical Cancer Research.
Authors: Andrew B. Lassman (Division of Neuro-Oncology, Department of Neurology and the Herbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and New York-Presbyterian Hospital, New York, NY, USA); Juan Manuel Sepúlveda-Sánchez (Hospital Universitario 12 De Octubre, Madrid, Spain); Timothy Cloughesy (University of California-Los Angeles); Miguel J. Gil-Gil (Institut Catal d'Oncologia, Hospitalet de Llobregat, Barcelona, Spain); Vinay K. Puduvalli (Ohio State University Wexner Medical Center); Jeffrey Raizer (Northwestern University); Filip Y. F. De Vos (University Medical Center Utrecht, Utrecht University, The Netherlands); Patrick Y. Wen (Dana-Farber Cancer Institute); Nicholas Butowski (University of California San Francisco); Paul M. J. Clement (Leuven Cancer Institute, KU Leuven, Belgium); Morris D. Groves (Texas Oncology PA); Crist bal Belda-Iniesta (Hospital Universitario HM Sanchinarro, Madrid, Spain); Pierre Giglio (Ohio State University Wexner Medical Center); Harris S. Soifer (QED Therapeutics); Steven Rowsey (QED Therapeutics); Cindy Xu (QED Therapeutics); Francesca Avogadri (QED Therapeutics); Ge Wei (QED Therapeutics); Susan Moran (QED Therapeutics); and Patrick Roth (University of Zurich, Zurich, Switzerland).
The study was sponsored by Novartis and QED Therapeutics, an affiliate of BridgeBio Pharma.