Calcinosis cutis dermatologic toxicity associated with fibroblast growth factor receptor inhibitor for the treatment of Wilms tumor

Arudra, Krishna C.; Patel, Ravi; Tetzlaff, Michael T.; Hymes, Sharon R.; Subbiah, Vivek; Meric‐Bernstam, Funda; Torres‐Cabala, Carlos A.; Aung, Phyu P.; Nagarajan, Priyadharsini; Diab, Adi; Prieto, Víctor G.; Nelson, Kelly C.

doi:10.1111/cup.13319

Cited by 22 publications

(23 citation statements)

References 21 publications

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“…We found 29 completed studies evaluating FGFR -targeting drugs in 11 of 14 cancer types analyzed in the off-label estimations (Table 2). 12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38 There were 8 (27.6%) case reports, 1 (3.4%) case series, 9 (31.0%) phase 1 studies, 2 (6.9%) phase 1/2 studies, and 9 (31.0%) phase 2 studies. While 2 phase 2 trials (22.2%) were randomized, the rest were noncomparator trials.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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“…A rare skin/soft tissue reaction that has been observed in patients undergoing treatment with FGFR inhibitors is calcinosis cutis, a condition in which calcium salts are deposited in the skin and subcutaneous tissues. This has been reported in one patient treated with infigratinib [53] and another treated with pemigatinib [54]. Of further interest is the risk of nonuremic calciphylaxis, or intimal vascular calcifications, resulting in vascular thrombosis and extensive skin necrosis resulting in grade 3 and 4 cutaneous ulcerations.…”

Section: Dermatologic Events In Patients Treated With Fgfr Tkis: Skinmentioning

confidence: 99%

Dermatologic Adverse Events Associated with Selective Fibroblast Growth Factor Receptor Inhibitors: Overview, Prevention, and Management Guidelines

et al. 2020

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Fibroblast growth factor receptor (FGFR) tyrosine kinases, which are expressed on the cell membrane, are involved in a wide range of biological functions such as cell proliferation, survival, migration, and differentiation. The identification of FGFR fusions and other alterations in a wide range of solid tumors, including cholangiocarcinoma and bladder cancer, has resulted in the development of several selective FGFR inhibitors for use in these indications, for example, infigratinib, erdafitinib, derazantinib, pemigatinib, and futibatinib. In addition to the typical adverse events associated with tyrosine kinases, the FGFR inhibitors appear to give rise to a number of adverse events affecting the skin. Here we describe these skin events, which include the more common nail adverse events (e.g., onycholysis), palmar-plantar erythrodysesthesia syndrome, and stomatitis, as well as less common reactions such as calciphylaxis. This review aims to provide oncologists with an understanding of these dermatologic events and proposes guidelines for the management of treatment-emergent dermatologic adverse events. Awareness of possible adverse events associated with specific drugs should allow physicians to educate patients as to what to expect and implement effective management plans at the earliest possible opportunity, thereby preventing premature discontinuation while maintaining patient quality of life. The Oncologist 2020;25:1-11 Implications for Practice: Identification of fibroblast growth factor receptor (FGFR) aberrations in cholangiocarcinoma and bladder cancer led to development of selective FGFR inhibitors for these indications, based on clinical benefit and safety profiles. The most frequent adverse events (AEs) include those affecting skin, hair, and nails, a unique class effect of these agents. These are usually mild to moderate in severity. This work reviewed skin AEs reported with FGFR inhibitors and provides management guidelines for physicians, aiming to increase awareness of skin events and provide effective treatment strategies. Early intervention and effective management may improve treatment adherence, optimize outcomes, and improve quality of life.

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“…[156][157][158] Altered calcium-phosphate homeostasis resulting in hyperphosphatemia is a frequent adverse event from FGFR inhibitors and hyperphosphatemia occurs in 45% to 100% of patients treated with pan-FGFR and FGFR1-3 inhibitors. 158,159 Calcinosis cutis and calciphylaxis are infrequent dermatologic toxicities from FGFR inhibitors, [160][161][162] however, awareness of this type of adverse skin reaction and monitoring of phosphate levels are critical in these patients.…”

Section: Fgfr Inhibitorsmentioning

confidence: 99%

Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy

et al. 2021

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Background: Advances in molecular biology and genetics have contributed to breakthrough treatments directed at specific pathways associated with the development of cancer. Small-molecule inhibitors (Nibs) aimed at a variety of cellular pathways have been efficacious; however, they are associated with significant dermatologic toxicities. Methods: We conducted a comprehensive review of dermatologic toxicities associated with Nibs categorized into the following five groups: (a) mitogen-activated protein kinase; (b) growth factor/multi-tyrosine kinase; (c) cell division/DNA repair; (d) signaling associated with myeloproliferative neoplasms; and (e) other signaling pathways. Prospective phase I, II, or III clinical trials, retrospective literature reviews, systematic reviews/meta-analyses, and case reviews/reports were included for analysis.Results: Dermatologic toxicities reviewed were associated with every class of Nibs and ranged from mild to severe or life-threatening adverse skin reactions.Inflammatory reactions manifesting as maculopapular, papulopustular/acneiform, and eczematous lesions were frequent types of dermatologic toxicities seen with Nibs.Squamous cell carcinoma with keratoacanthoma-like features was associated with a subset of Nibs. Substantial overlap in dermatologic toxicities was found between Nibs.Conclusions: Dermatologic toxicities from Nibs are diverse and may overlap between classes of Nibs. Recognition of the various types of toxicities from Nibs is critical for patient care in the era of "oncodermatology/dermatopathology."

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Calcinosis cutis dermatologic toxicity associated with fibroblast growth factor receptor inhibitor for the treatment of Wilms tumor

Cited by 22 publications

References 21 publications

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

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

Dermatologic Adverse Events Associated with Selective Fibroblast Growth Factor Receptor Inhibitors: Overview, Prevention, and Management Guidelines

Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy

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