Estimation of Percentage of Patients With Fibroblast Growth Factor Receptor Alterations Eligible for Off-label Use of Erdafitinib

Abstract

IMPORTANCE When a novel drug is granted accelerated approval, both its on-label and off-label uses must be taken into account. OBJECTIVES To estimate the potential upper bound of off-label use of erdafitinib to treat advanced cancer with fibroblast growth factor receptor gene (FGFR) alterations, compare it to the upper bound of on-label use in urothelial cancer, and to review studies that may support off-label use. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used frequency data on FGFR alterations by cancer type and the estimated number of deaths from all cancers for 2019 in the United States. Mortality statistics were used as surrogates for patients with advanced cancer. Analysis was conducted in May 2019. EXPOSURE Percentage of patients with an FGFR2 or FGFR3 alteration. MAIN OUTCOMES AND MEASURES Estimated number of patients with advanced cancer expressing an FGFR2 or FGFR3 alteration eligible for off-label use of erdafitinib by cancer type; number of studies investigating FGFR-targeting drugs for patients with cancer; and number of ongoing clinical trials on erdafitinib by cancer type. RESULTS A total of 15 cancer types had reported FGFR alterations. Of 455 440 estimated patients who died of cancer in 2019, 17 019 (3.7%) were estimated to have FGFR2 or FGFR3 alterations. Of these patients, 12 955 (76.1%) could be eligible for off-label treatment with erdafitinib. A total of 29 completed studies evaluated FGFR-targeting drugs in 11 cancer types, and 10 ongoing studies are studying erdafitinib for different oncological indications. CONCLUSIONS AND RELEVANCE This study indicates that the potential for off-label use of FGFR inhibitors such as erdafitinib spans a number of cancer types and a large patient population. Systematic trials exploring off-label uses may be desirable for drugs that target clear, identifiable molecular alterations because this may be more efficient than off-label use in identifying clinical scenarios where the agent has activity.

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors

“…Moreover, erdafitinib is limited to patients with FGFR2/3 mutation or fusion (15%-20% of patients depending on cancer type). 11 Hence, new agents are still needed.…”

Case Report: Molecular Features and Treatment Options for Small Bowel Adenocarcinoma

“…This study led to the approval of erdafitinib for second-line advanced urothelial cancer patients with FGFR2/3 alterations ( 20 ). A subsequent study estimated the off-label use of several drugs, including erdafitinib and determined that the potential off-label erdafitinib users could be up to 3 times greater than under the current recommendations ( 21 ). On the other hand, infigratinib is a potent FGFR1-3 inhibitor with demonstrated single-agent antitumor activity in FGFR3 mutant early-stage urothelial cancer patients ( 22 ).…”

FGFR Pathway Inhibition in Gastric Cancer: The Golden Era of an Old Target?

“…Since then, refinement of molecular techniques for the design of target-specific molecules and careful selection of patients have demonstrated the potential benefit of FGFR blockade in the growing portfolio of cancer drugs, especially in tumors with poor survival, such as cholangiocarcinoma [44]. A recent study showed that among patients with tumors driven by FGFR aberrations, 76% would be considered ineligible for target therapy due to currently approved indications, comprising 15 different tumor types, potentially susceptible to therapy with TKIs [45].…”