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Conference Paper: Thyroid Immune-Related Adverse Events Among Cancer Patients Treated With Combination of Anti-PD1 and Anti-CTLA4 Immune-Checkpoint Inhibitors: Clinical Course and Outcomes

TitleThyroid Immune-Related Adverse Events Among Cancer Patients Treated With Combination of Anti-PD1 and Anti-CTLA4 Immune-Checkpoint Inhibitors: Clinical Course and Outcomes
Authors
Keywordshypothyroidism
immunotherapy
survival
neoplasms
thyroid diseases
Issue Date2021
PublisherOxford University Press. The Journal's web site is located at https://academic.oup.com/jes/
Citation
Annual Meeting of the Endocrine Society (ENDO 2021), Virtual Meeting, USA, 20-23 March 2021. In Journal of the Endocrine Society, 2021, v. 5 n. Suppl. 1, p. A847 How to Cite?
AbstractIntroduction: Thyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among cancer patients treated with anti-PD1 and anti-PDL1 monotherapies. There are scanty data in the literature thus far about the clinical course and prognostic significance of thyroid irAEs in the routine clinical use of combination anti-PD1/anti-CTLA4 treatment in advanced cancer patients. We evaluated the clinical course and predictors of thyroid irAEs, in relation to outcomes of advanced cancer patients treated with combination anti-PD1/anti-CTLA4. Method: We conducted a territory-wide study and identified advanced cancer patients who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Patients were excluded if (i) they had a history of thyroid disorder or thyroid cancer, (ii) immune checkpoint inhibitor-related endocrinopathies occurred before the commencement of combination anti-PD1/anti-CTLA4, (iii) they were on concurrent tyrosine kinase inhibitor (TKI), (iv) baseline thyroid function tests (TFTs) were absent or abnormal, and (v) the duration of follow-up was <30 days. TFTs were monitored every three weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes. The initial presentation was classified into hypothyroidism (overt if TSH >4.8 mIU/L and fT4 <12 pmol/L; subclinical if TSH >4.8 mIU/L and fT4 12-23 pmol/L) and thyrotoxicosis (overt if TSH <0.35 mIU/L and fT4 >23 pmol/L; subclinical if TSH <0.35 mIU/L and fT4 12-23 pmol/L). Results: One hundred and three patients were included (median age: 59 years; 71.8% men). Around half of patients had hepatocellular carcinoma. About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n=4; subclinical, n=2), and 11 with hypothyroidism (overt, n=2; subclinical, n=9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (OR 3.67, 95% CI 1.19-11.4, p=0.024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was associated with better overall survival (adjusted hazard ratio 0.39, 95% CI 0.19-0.79, p=0.009), independent of prior exposure to anti-PD1 (p=0.386) and prior TKI exposure (p=0.155). Conclusion: Thyroid irAEs are common in routine clinical practice among advanced cancer patients treated with combination anti-PD1/anti-CTLA4, and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.
DescriptionIssue Section: Thyroid Autoimmunity, COVID-19 & Thyroid Disease
Persistent Identifierhttp://hdl.handle.net/10722/300812
ISSN

 

DC FieldValueLanguage
dc.contributor.authorLui, TWD-
dc.contributor.authorLee, CHP-
dc.contributor.authorTang, V-
dc.contributor.authorFong, CHY-
dc.contributor.authorLee, ACH-
dc.contributor.authorChiu, JWY-
dc.contributor.authorLeung, RCY-
dc.contributor.authorKwok, GGW-
dc.contributor.authorLi, BCH-
dc.contributor.authorCheung, TT-
dc.contributor.authorWoo, YC-
dc.contributor.authorLam, KSL-
dc.contributor.authorYau, TCC-
dc.date.accessioned2021-07-06T03:10:36Z-
dc.date.available2021-07-06T03:10:36Z-
dc.date.issued2021-
dc.identifier.citationAnnual Meeting of the Endocrine Society (ENDO 2021), Virtual Meeting, USA, 20-23 March 2021. In Journal of the Endocrine Society, 2021, v. 5 n. Suppl. 1, p. A847-
dc.identifier.issn2472-1972-
dc.identifier.urihttp://hdl.handle.net/10722/300812-
dc.descriptionIssue Section: Thyroid Autoimmunity, COVID-19 & Thyroid Disease-
dc.description.abstractIntroduction: Thyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among cancer patients treated with anti-PD1 and anti-PDL1 monotherapies. There are scanty data in the literature thus far about the clinical course and prognostic significance of thyroid irAEs in the routine clinical use of combination anti-PD1/anti-CTLA4 treatment in advanced cancer patients. We evaluated the clinical course and predictors of thyroid irAEs, in relation to outcomes of advanced cancer patients treated with combination anti-PD1/anti-CTLA4. Method: We conducted a territory-wide study and identified advanced cancer patients who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Patients were excluded if (i) they had a history of thyroid disorder or thyroid cancer, (ii) immune checkpoint inhibitor-related endocrinopathies occurred before the commencement of combination anti-PD1/anti-CTLA4, (iii) they were on concurrent tyrosine kinase inhibitor (TKI), (iv) baseline thyroid function tests (TFTs) were absent or abnormal, and (v) the duration of follow-up was <30 days. TFTs were monitored every three weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes. The initial presentation was classified into hypothyroidism (overt if TSH >4.8 mIU/L and fT4 <12 pmol/L; subclinical if TSH >4.8 mIU/L and fT4 12-23 pmol/L) and thyrotoxicosis (overt if TSH <0.35 mIU/L and fT4 >23 pmol/L; subclinical if TSH <0.35 mIU/L and fT4 12-23 pmol/L). Results: One hundred and three patients were included (median age: 59 years; 71.8% men). Around half of patients had hepatocellular carcinoma. About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n=4; subclinical, n=2), and 11 with hypothyroidism (overt, n=2; subclinical, n=9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (OR 3.67, 95% CI 1.19-11.4, p=0.024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was associated with better overall survival (adjusted hazard ratio 0.39, 95% CI 0.19-0.79, p=0.009), independent of prior exposure to anti-PD1 (p=0.386) and prior TKI exposure (p=0.155). Conclusion: Thyroid irAEs are common in routine clinical practice among advanced cancer patients treated with combination anti-PD1/anti-CTLA4, and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at https://academic.oup.com/jes/-
dc.relation.ispartofJournal of the Endocrine Society-
dc.relation.ispartofAnnual Meeting of the Endocrine Society (ENDO 2021)-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjecthypothyroidism-
dc.subjectimmunotherapy-
dc.subjectsurvival-
dc.subjectneoplasms-
dc.subjectthyroid diseases-
dc.titleThyroid Immune-Related Adverse Events Among Cancer Patients Treated With Combination of Anti-PD1 and Anti-CTLA4 Immune-Checkpoint Inhibitors: Clinical Course and Outcomes-
dc.typeConference_Paper-
dc.identifier.emailLui, TWD: dtwlui@hku.hk-
dc.identifier.emailLee, CHP: pchlee@hku.hk-
dc.identifier.emailTang, V: vyftang@hku.hk-
dc.identifier.emailLee, ACH: achlee@hku.hk-
dc.identifier.emailChiu, JWY: jwychiu@hku.hk-
dc.identifier.emailLeung, RCY: leungrcy@hku.hk-
dc.identifier.emailCheung, TT: cheung68@hku.hk-
dc.identifier.emailWoo, YC: wooyucho@hku.hk-
dc.identifier.emailLam, KSL: ksllam@hku.hk-
dc.identifier.emailYau, TCC: tyaucc@hku.hk-
dc.identifier.authorityLui, TWD=rp02803-
dc.identifier.authorityLee, CHP=rp02043-
dc.identifier.authorityChiu, JWY=rp01917-
dc.identifier.authorityCheung, TT=rp02129-
dc.identifier.authorityLam, KSL=rp00343-
dc.identifier.authorityYau, TCC=rp01466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1210/jendso/bvab048.1729-
dc.identifier.hkuros323117-
dc.identifier.volume5-
dc.identifier.issueSuppl. 1-
dc.identifier.spageA847-
dc.identifier.epageA847-
dc.publisher.placeUnited States-

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