Cabozantinib in Patients with Advanced Merkel Cell Carcinoma

Rabinowits, Guilherme; Lezcano, Cecilia; Catalano, Paul J.; Mchugh, P.; Becker, Hailey; Reilly, Mary M.; Huang, Julian; Tyagi, Ayushi; Thakuria, Manisha; Bresler, Scott C.; Sholl, Lynette M.; Shapiro, Geoffrey I.; Haddad, Robert I.; DeCaprio, James A.

doi:10.1634/theoncologist.2017-0552

Cited by 37 publications

(32 citation statements)

References 34 publications

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“…Pazopanib inhibits several tyrosine kinases, including VEGFR, PDGFR, FGFR and KIT; this agent has been associated with clinical benefit in case reports 182 and was investigated in a trial in the UK 8 . A clinical trial involving the multikinase inhibitor cabozantinib in patients with advanced-stage, platinum-refractory MCC was terminated prematurely owing to poor tolerability and a lack of responses in the first eight patients treated 183 . Of note, evidence for ERK activation in MCCs is lacking 88 , and HRAS mutations do not render MCC cell lines responsive to MEK inhibition 7 .…”

Section: Investigational Therapies In MCCmentioning

confidence: 99%

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities

et al. 2018

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Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer associated with advanced age and immunosuppression. Over the last decade, it has been discovered that MCC tumors are associated with either integrated Merkel cell polyomavirus, which likely drives tumorigenesis, or a high burden of UV-induced somatic mutations. Both virus-positive and virus-negative MCC tumors are immunogenic and PD-(L)1 checkpoint blockade has proven to be highly effective in treating most patients with metastatic MCC; however, about 50% of treated patients do not experience long term tumor control. Despite these rapid advances in the understanding and management of MCC, many basic, translational, and clinical research questions remain. In March 2018, an International Workshop on Merkel Cell Carcinoma Research was held at the National Cancer Institute where academic, government, and industry thought leaders met to identify high priority research questions. Here we review the biology and treatment of MCC and report the conclusions of the Workshop.

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Section: Investigational Therapies In MCCmentioning

confidence: 99%

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities

et al. 2018

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“…However, little is known about their clinical benefit in MCC. To date, only one clinical trial of TKIs (NCT02036476) has been registered ( 19 ); however, due to toxicity and a lack of response, it was closed prematurely. In addition, some case reports have demonstrated the efficiency of TKIs, such as pazopanib and cabozantinib ( 20 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Favorable Response to the Tyrosine Kinase Inhibitor Apatinib in Recurrent Merkel Cell Carcinoma

2021

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BackgroundAs angiogenesis is an essential step in tumor growth and metastasis, the tyrosine kinase inhibitor (TKI) apatinib has become a revolutionary anticancer therapy across various malignancies. However, its efficiency and safety in Merkel cell carcinoma (MCC) are uncertain.Case presentationThe current study described the case of a 91-year-old man who presented with a 3.2 × 3.0 × 2.2 cm rapidly growing, solitary tumor of the right lower eyelid. It was diagnosed as MCC pathologically. Twenty-seven days after the surgery, the patient returned to the hospital with recurrent MCC. Apatinib was then administered to this patient. The patient had a complete response (CR) to apatinib after 4.4 months of targeted therapy. Twenty-seven months of progression-free survival (PFS) was achieved with controllable treatment-related adverse events (AEs).ConclusionTreatment with apatinib demonstrated clinical benefit in our patient with recurrent MCC, highlighting its potential utility in other MCC patients. Further clinical trials are needed to determine the efficacy and safety of apatinib in MCC patients.

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“…Thyroiditis was developed by 7%. Among the other patients, 30% had elevation of TSH or FT4 above the normal range, and serum T3/reverse T3 ratio and the (T3/T4) ×100 ratio decreased (46). Eight patients were accrued, then the study was closed prematurely owing to toxicity and lack of responses.…”

Section: Sunitinib Cediranib and Axitinibmentioning

confidence: 99%

“…Eight patients were accrued, then the study was closed prematurely owing to toxicity and lack of responses. Four of the eight patients (50%) had hypothyroidism (46).…”

Section: Sunitinib Cediranib and Axitinibmentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: Endocrine-metabolic effects of treatment with multikinase inhibitors

Fallahi

Ferrari

Elia

et al. 2021

European Journal of Endocrinology

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Tyrosine kinase inhibitors (TKIs) are emerging as potentially effective options in the treatment of cancer, acting on the pathways involved in growth, avoidance of apoptosis, invasiveness, angiogenesis, and local and distant spread. TKIs induce significant adverse effects, that can negatively affect patients’ quality of life. The most common adverse events (AEs) include fatigue, hand–foot skin reaction, decreased appetite, nausea, diarrhoea, hypertension, vomiting, weight loss, endocrinopaties and metabolic disorders. Patients in therapy with TKIs can develop endocrine-metabolic disorders, including dyslipidemia (∼50%), diabetes (∼15–40%), and dysthyroidism (∼20%). In some cases, patients show an improved glycemia or hypoglycemia. The effects of TKIs on adrenal or gonadal function are still not completely known. It was shown a higher prevalence of subclinical hypocortisolism in patients treated with imatinib, while an increase of cortisol was reported in patients receiving vandetanib. Long-term treatment with imatinib could impact significantly the ovarian reserve and embryo developmental capacity. It is important to evaluate patients, measure glucose levels, and manage hyperglycemia. Mild treatment-related hyperglycemia can be controlled modifying the diet and with exercise, while grade 3 and 4 hyperglycemia can lead to dose reductions and/or oral antihyperglycemic therapy. Regarding thyroid dysfunctions, it is recommendable to measure the thyroid-stimulating hormone (TSH)/free thyroxine (FT4) levels before starting the therapy, and every 3–4 weeks during the first 6 months as changes in FT4 levels precede the changes in TSH by 3–6 weeks. Additional studies are necessary to definitely clarify the mechanism of TKIs-induced endocrine-metabolic effects.

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Cabozantinib in Patients with Advanced Merkel Cell Carcinoma

Cited by 37 publications

References 34 publications

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities

Case Report: Favorable Response to the Tyrosine Kinase Inhibitor Apatinib in Recurrent Merkel Cell Carcinoma

THERAPY OF ENDOCRINE DISEASE: Endocrine-metabolic effects of treatment with multikinase inhibitors

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