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Lenvatinib treatment for thyroid cancer in COVID era: safety in a patient with lung metastases and SARS-CoV-2 infection

Lenvatinib treatment for thyroid cancer in COVID era: safety in a patient with lung metastases... 1116 Case report Lenvatinib treatment for thyroid cancer in COVID era: safety in a patient with lung metastases and SARS-CoV-2 infection Pietro Locantore, Valeria Del Gatto, Andrea Corsello and Alfredo Pontecorvi During the coronavirus disease 2019 (COVID-19) and could continue treatment. Despite concerns over pandemic, clinicians are required to manage patient care COVID-19, clinicians should not overlook treatment of for pre-existing conditions. Currently, there are no clear pre-existing diseases or discontinue treatment, particularly indications regarding the management of lenvatinib- for cancer. Clinicians should evaluate a patient’s history treated patients for radioiodine-refractory thyroid cancer and clinical presentation, monitoring the patient to reduce and severe acute respiratory syndrome coronavirus 2 the development of complications in high-risk settings, (SARS-CoV-2) infection. A 74-year-old male patient was avoiding treatment discontinuation. Anti-Cancer Drugs 32: treated with lenvatinib since March 2019, with disease 1116–1117 Copyright © 2021 The Author(s). Published by recurrence in the thyroid bed and bilateral multiple lung Wolters Kluwer Health, Inc. metastases. The patient partially responded to treatment, Anti-Cancer Drugs 2021, 32:1116–1117 with reduction in lung metastases. In September 2019, Keywords: anti-VEGFR receptor, case report, coronavirus disease 2019, the patient tested positive for SARS-CoV-2 and isolated lenvatinib, thyroid cancer at home. Initially asymptomatic, the patient developed Unit of Endocrinology, Fondazione Policlinico Gemelli – IRCCS, Università mild symptoms. Lenvatinib treatment continued with daily Cattolica del Sacro Cuore, Rome monitoring of vital signs. After telemedicine consultation Correspondence to Pietro Locantore, MD, PhD, Unit of Endocrinology, of patient’s clinical condition, severity of symptoms was Fondazione Policlinico Gemelli – IRCCS, Università Cattolica del Sacro Cuore low. He tested negative for SARS-CoV-2 21 days after 00168, Rome Tel: +00390630154165; e-mail: pietro.locantore@icloud.com testing positive. The patient received the full course of lenvatinib treatment. This is the first reported case of Received 15 May 2021 Revised form accepted 30 May 2021 a lenvatinib-treated patient who developed COVID-19 Introduction Case presentation Severe acute respiratory syndrome coronavirus 2 (SARS- We present a case of a 74-year-old male patient treated CoV-2) and coronavirus disease 2019 (COVID-19) have with lenvatinib for advanced RR-DTC, since March emerged as a global pandemic. Patients with either a 2019, with disease recurrence in the thyroid bed and history of or active cancer may be at an increased risk bilateral multiple lung metastases (maximum diameter of contracting the virus and developing complications 7.4 × 5.7 cm). [1]. Patients on oral chemotherapy with a history of He started treatment at 24 mg/day lenvatinib; however, lung disease are at particular risk, due to intercurrent following weight loss and nausea in September 2019, disease potentially worsening respiratory function. It the dose was reduced to 18 mg/day. He showed partial is paramount that cancer treatment continues whilst response to treatment, with a progressive reduction of protecting patients against the virus. The aim of this lung metastases (actual maximum diameter 6.5 × 3.2 cm). case report is to determine the safety profile of contin- Whilst on treatment in September 2020, the patient tested uing lenvatinib treatment for patients with radioiodine positive for SARS-CoV-2 via a nasopharyngeal swab. The refractory (RR) advanced differentiated thyroid cancer patient isolated at home and was initially asymptomatic. (DTC), given that COVID-19 may worsen respiratory After a few days, he developed mild symptoms (cough, function. diarrhea, and worsening asthenia), but never experienced Advanced DTC is treated by total or near-total thyroidec- anosmia or fever. We decided not to discontinue lenvati- tomy, followed, where necessary, by radioiodine ( I) and nib treatment and daily monitoring of vital signs was thyroid hormone suppressive therapy [2]. However, some performed, including blood pressure, body temperature, patients are resistant to I, and cytotoxic chemotherapy and oxygen saturation. The evaluation of adverse events is not very effective in patients with metastatic RR-DTC. (AEs) and the patient’s clinical condition was carried out Alternatively, lenvatinib, an oral multikinase inhibitor is a by telemedicine. Due to the low severity of symptoms, novel therapy to manage DTC [3]. chest imaging was not performed. The patient performed LWW a new nasopharyngeal swab 21 days after the detection of SARS-CoV-2 and tested negative. Despite our con- This is an open access article distributed under the Creative Commons Attribution cerns, we observed no severe respiratory, gastrointestinal, License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduc- tion in any medium, provided the original work is properly cited. or hematopoietic complications, and the patient needed 0959-4973 Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. DOI: 10.1097/CAD.0000000000001097 Copyright © 2021 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Levatinib in COVID era Locantore et al. 1117 neither specific therapy for COVID-19 nor lenvatinib continue for patients testing positive for SARS-CoV-2. interruption or discontinuation for the full course of the The continuation of treatment for patients with cancer intercurrent disease. is crucial for disease management. Careful monitoring of patients by clinicians could ensure lenvatinib treatment continues whilst managing the complications in high-risk Discussion settings due to the COVID-19 pandemic [7]. In sum- Patients with cancer are typically older with more comor- mary, this case report demonstrates that lenvatinib treat- bidities and may be immunocompromised by treatment ment can continue if patients are carefully monitored for or through the nature of cancer [1]. Patients with cancer COVID-19-associated complications. Studies with larger have an increased risk for COVID-19 related morbidity samples and longer follow-up periods are required to and mortality, regardless of whether they have active determine the safety of continuing cancer treatment for cancer or are being treated [1]. Careful monitoring of patients with cancer and COVID-19. both COVID-19 symptoms and anti-cancer treatment associated AEs are important for assessing treatment Acknowledgements continuation. To date, this is the first reported case of The authors confirm that the research meets the ethics a lenvatinib-treated patient who developed COVID- guidelines, including adherence to the legal require- 19, with the patient able to continue treatment without ments of the country where the study was performed. experiencing any additional AEs. As data are limited, this report is an important indicator of the safety of All authors have equally contributed. All authors have continuing lenvatinib treatment during the COVID- read and approved the article. 19 pandemic and could be more widely generalized to patients with COVID-19 infections for other cancer Written consent for publication was obtained from the types receiving anticancer treatments. study participant. Patients with RR-DTC treated with lenvatinib were enrolled in an Italian expanded access program to char- The dataset used during the current study is available acterize the safety profile [4]. All patients experienced from the corresponding author on reasonable request. at least one AE, the most frequent AEs reported were hypertension (80.5%), fatigue (58.3%), diarrhea (36.1%), Conflicts of interest stomatitis (33.3%), hand-foot syndrome (33.3%), and There are no conflicts of interest. weight loss (30.5%) [4]. References Despite the complications of COVID-19 and the 1 Kuderer NM, Choueiri TK, Shah DP, Shyr Y, Rubinstein SM, Rivera DR, et al.; COVID-19 and Cancer Consortium. Clinical impact of COVID- increased risk of mortality and morbidity for patients 19 on patients with cancer (CCC19): a cohort study. Lancet 2020; with cancer and SARS-CoV-2, continuing lenvatinib 395:1907–1918. treatment should be favored over treatment discontin- 2 Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet 2016;388:2783–2795. uation, given the treatment benefits. In a phase 3 trial, 3 Valerio L, Pieruzzi L, Giani C, Agate L, Bottici V, Lorusso L, et al. Targeted lenvatinib treatment significantly improved progres- therapy in thyroid cancer: state of the art. Clin Oncol (R Coll Radiol) 2017; sion-free survival (PFS) for patients with RR-DTC, with 29:316–324. 4 Giani C, Valerio L, Bongiovanni A, Durante C, Grani G, Ibrahim T, et al. a 14.6-month longer median PFS vs. patients receiving Safety and quality-of-life data from an Italian expanded access program placebo (P < 0.001) (5). Lenvatinib significantly improved of lenvatinib for treatment of thyroid cancer. Thyroid 2021; 31:224– response rate (64.7% in the lenvatinib group vs. 1.5% in 232. 5 Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. the placebo group, P < 0.001) [5]. In a post hoc analysis Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J performed on patients enrolled in the SELECT study, Med 2015; 372:621–630. 6 Tahara M, Brose MS, Wirth LJ, Suzuki T, Miyagishi H, Fujino K, et al. higher rates of dose interruption or dose reduction had a Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study negative impact on PFS [6]. in patients with radioiodine-refractory differentiated thyroid cancer. Eur J Cancer 2019; 106:61–68. In the present case, we could hypothesize that effective 7 National Comprehensive Cancer Network. Coronavirus Disease 2019 monitoring of a patient’s AEs and clinical presentation (COVID-19) Resources for the Cancer Care Community. 2020. www.nccn. org/covid-19/default.aspx (2020 Version 1). is important in deciding if lenvatinib treatment should Copyright © 2021 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Anti-Cancer Drugs Wolters Kluwer Health

Lenvatinib treatment for thyroid cancer in COVID era: safety in a patient with lung metastases and SARS-CoV-2 infection

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Publisher
Wolters Kluwer Health
Copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
ISSN
0959-4973
eISSN
1473-5741
DOI
10.1097/cad.0000000000001097
Publisher site
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Abstract

1116 Case report Lenvatinib treatment for thyroid cancer in COVID era: safety in a patient with lung metastases and SARS-CoV-2 infection Pietro Locantore, Valeria Del Gatto, Andrea Corsello and Alfredo Pontecorvi During the coronavirus disease 2019 (COVID-19) and could continue treatment. Despite concerns over pandemic, clinicians are required to manage patient care COVID-19, clinicians should not overlook treatment of for pre-existing conditions. Currently, there are no clear pre-existing diseases or discontinue treatment, particularly indications regarding the management of lenvatinib- for cancer. Clinicians should evaluate a patient’s history treated patients for radioiodine-refractory thyroid cancer and clinical presentation, monitoring the patient to reduce and severe acute respiratory syndrome coronavirus 2 the development of complications in high-risk settings, (SARS-CoV-2) infection. A 74-year-old male patient was avoiding treatment discontinuation. Anti-Cancer Drugs 32: treated with lenvatinib since March 2019, with disease 1116–1117 Copyright © 2021 The Author(s). Published by recurrence in the thyroid bed and bilateral multiple lung Wolters Kluwer Health, Inc. metastases. The patient partially responded to treatment, Anti-Cancer Drugs 2021, 32:1116–1117 with reduction in lung metastases. In September 2019, Keywords: anti-VEGFR receptor, case report, coronavirus disease 2019, the patient tested positive for SARS-CoV-2 and isolated lenvatinib, thyroid cancer at home. Initially asymptomatic, the patient developed Unit of Endocrinology, Fondazione Policlinico Gemelli – IRCCS, Università mild symptoms. Lenvatinib treatment continued with daily Cattolica del Sacro Cuore, Rome monitoring of vital signs. After telemedicine consultation Correspondence to Pietro Locantore, MD, PhD, Unit of Endocrinology, of patient’s clinical condition, severity of symptoms was Fondazione Policlinico Gemelli – IRCCS, Università Cattolica del Sacro Cuore low. He tested negative for SARS-CoV-2 21 days after 00168, Rome Tel: +00390630154165; e-mail: pietro.locantore@icloud.com testing positive. The patient received the full course of lenvatinib treatment. This is the first reported case of Received 15 May 2021 Revised form accepted 30 May 2021 a lenvatinib-treated patient who developed COVID-19 Introduction Case presentation Severe acute respiratory syndrome coronavirus 2 (SARS- We present a case of a 74-year-old male patient treated CoV-2) and coronavirus disease 2019 (COVID-19) have with lenvatinib for advanced RR-DTC, since March emerged as a global pandemic. Patients with either a 2019, with disease recurrence in the thyroid bed and history of or active cancer may be at an increased risk bilateral multiple lung metastases (maximum diameter of contracting the virus and developing complications 7.4 × 5.7 cm). [1]. Patients on oral chemotherapy with a history of He started treatment at 24 mg/day lenvatinib; however, lung disease are at particular risk, due to intercurrent following weight loss and nausea in September 2019, disease potentially worsening respiratory function. It the dose was reduced to 18 mg/day. He showed partial is paramount that cancer treatment continues whilst response to treatment, with a progressive reduction of protecting patients against the virus. The aim of this lung metastases (actual maximum diameter 6.5 × 3.2 cm). case report is to determine the safety profile of contin- Whilst on treatment in September 2020, the patient tested uing lenvatinib treatment for patients with radioiodine positive for SARS-CoV-2 via a nasopharyngeal swab. The refractory (RR) advanced differentiated thyroid cancer patient isolated at home and was initially asymptomatic. (DTC), given that COVID-19 may worsen respiratory After a few days, he developed mild symptoms (cough, function. diarrhea, and worsening asthenia), but never experienced Advanced DTC is treated by total or near-total thyroidec- anosmia or fever. We decided not to discontinue lenvati- tomy, followed, where necessary, by radioiodine ( I) and nib treatment and daily monitoring of vital signs was thyroid hormone suppressive therapy [2]. However, some performed, including blood pressure, body temperature, patients are resistant to I, and cytotoxic chemotherapy and oxygen saturation. The evaluation of adverse events is not very effective in patients with metastatic RR-DTC. (AEs) and the patient’s clinical condition was carried out Alternatively, lenvatinib, an oral multikinase inhibitor is a by telemedicine. Due to the low severity of symptoms, novel therapy to manage DTC [3]. chest imaging was not performed. The patient performed LWW a new nasopharyngeal swab 21 days after the detection of SARS-CoV-2 and tested negative. Despite our con- This is an open access article distributed under the Creative Commons Attribution cerns, we observed no severe respiratory, gastrointestinal, License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduc- tion in any medium, provided the original work is properly cited. or hematopoietic complications, and the patient needed 0959-4973 Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. DOI: 10.1097/CAD.0000000000001097 Copyright © 2021 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Levatinib in COVID era Locantore et al. 1117 neither specific therapy for COVID-19 nor lenvatinib continue for patients testing positive for SARS-CoV-2. interruption or discontinuation for the full course of the The continuation of treatment for patients with cancer intercurrent disease. is crucial for disease management. Careful monitoring of patients by clinicians could ensure lenvatinib treatment continues whilst managing the complications in high-risk Discussion settings due to the COVID-19 pandemic [7]. In sum- Patients with cancer are typically older with more comor- mary, this case report demonstrates that lenvatinib treat- bidities and may be immunocompromised by treatment ment can continue if patients are carefully monitored for or through the nature of cancer [1]. Patients with cancer COVID-19-associated complications. Studies with larger have an increased risk for COVID-19 related morbidity samples and longer follow-up periods are required to and mortality, regardless of whether they have active determine the safety of continuing cancer treatment for cancer or are being treated [1]. Careful monitoring of patients with cancer and COVID-19. both COVID-19 symptoms and anti-cancer treatment associated AEs are important for assessing treatment Acknowledgements continuation. To date, this is the first reported case of The authors confirm that the research meets the ethics a lenvatinib-treated patient who developed COVID- guidelines, including adherence to the legal require- 19, with the patient able to continue treatment without ments of the country where the study was performed. experiencing any additional AEs. As data are limited, this report is an important indicator of the safety of All authors have equally contributed. All authors have continuing lenvatinib treatment during the COVID- read and approved the article. 19 pandemic and could be more widely generalized to patients with COVID-19 infections for other cancer Written consent for publication was obtained from the types receiving anticancer treatments. study participant. Patients with RR-DTC treated with lenvatinib were enrolled in an Italian expanded access program to char- The dataset used during the current study is available acterize the safety profile [4]. All patients experienced from the corresponding author on reasonable request. at least one AE, the most frequent AEs reported were hypertension (80.5%), fatigue (58.3%), diarrhea (36.1%), Conflicts of interest stomatitis (33.3%), hand-foot syndrome (33.3%), and There are no conflicts of interest. weight loss (30.5%) [4]. References Despite the complications of COVID-19 and the 1 Kuderer NM, Choueiri TK, Shah DP, Shyr Y, Rubinstein SM, Rivera DR, et al.; COVID-19 and Cancer Consortium. Clinical impact of COVID- increased risk of mortality and morbidity for patients 19 on patients with cancer (CCC19): a cohort study. Lancet 2020; with cancer and SARS-CoV-2, continuing lenvatinib 395:1907–1918. treatment should be favored over treatment discontin- 2 Cabanillas ME, McFadden DG, Durante C. Thyroid cancer. Lancet 2016;388:2783–2795. uation, given the treatment benefits. In a phase 3 trial, 3 Valerio L, Pieruzzi L, Giani C, Agate L, Bottici V, Lorusso L, et al. Targeted lenvatinib treatment significantly improved progres- therapy in thyroid cancer: state of the art. Clin Oncol (R Coll Radiol) 2017; sion-free survival (PFS) for patients with RR-DTC, with 29:316–324. 4 Giani C, Valerio L, Bongiovanni A, Durante C, Grani G, Ibrahim T, et al. a 14.6-month longer median PFS vs. patients receiving Safety and quality-of-life data from an Italian expanded access program placebo (P < 0.001) (5). Lenvatinib significantly improved of lenvatinib for treatment of thyroid cancer. Thyroid 2021; 31:224– response rate (64.7% in the lenvatinib group vs. 1.5% in 232. 5 Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. the placebo group, P < 0.001) [5]. In a post hoc analysis Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J performed on patients enrolled in the SELECT study, Med 2015; 372:621–630. 6 Tahara M, Brose MS, Wirth LJ, Suzuki T, Miyagishi H, Fujino K, et al. higher rates of dose interruption or dose reduction had a Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study negative impact on PFS [6]. in patients with radioiodine-refractory differentiated thyroid cancer. Eur J Cancer 2019; 106:61–68. In the present case, we could hypothesize that effective 7 National Comprehensive Cancer Network. Coronavirus Disease 2019 monitoring of a patient’s AEs and clinical presentation (COVID-19) Resources for the Cancer Care Community. 2020. www.nccn. org/covid-19/default.aspx (2020 Version 1). is important in deciding if lenvatinib treatment should Copyright © 2021 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Journal

Anti-Cancer DrugsWolters Kluwer Health

Published: Nov 25, 2021

References