Endocrine Toxicity and Outcomes in Patients With Metastatic Malignancies Treated With Immune Checkpoint Inhibitors

Ashi, Suleiman I Al; Thapa, Bicky; Flores, Monica Velasquez; Ahmed, Ramsha; Rahim, Shab E Gul; Amir, Maryam; Alomari, Mohammad; Chadalavada, Pravallika; Morrison, Shannon L.; Bena, James; Hercbergs, Aleck; Lashin, Ossama; Daw, Hamed

doi:10.1210/jendso/bvab100

Cited by 14 publications

(17 citation statements)

References 41 publications

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“…Along with thyroid dysfunction, the impact of immune-related endocrine AEs on patient outcomes have also been investigated in 2 retrospective studies. 5,7 In a large retrospective analysis of 551 patients receiving nivolumab, atezolizumab, pembrolizumab, ipilimumab, or combination immunotherapy, endocrine toxicity most commonly occurred in those receiving ipilimumab monotherapy or a combination therapy containing ipilimumab. Time to immune-related endocrine effects was 9 weeks, and those developing endocrine toxicity demonstrated an improved overall survival (HR: 1.86, 95% CI: 1.39-2.49, P < .001).…”

Section: Discussionmentioning

confidence: 99%

“…To date, multiple studies have demonstrated improved outcomes for patients developing hypothyroidism from ICI therapy. [3][4][5]7 These studies were retrospective and included patients with advanced malignancy receiving multiple ICIs. In a study of 91 patients receiving atezolizumab or avelumab for various advanced malignancies, 21% developed new onset hypothyroidism defined as a TSH level higher than 4.3 µIU/mL and T4 level lower than 1.7 µIU/mL.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…2 Studies of patients receiving various ICIs for multiple malignancies have suggested that ICI-induced thyroiditis may be associated with improved overall survival in cancer patients. [3][4][5][6][7][8] In these studies, the onset of thyroid AEs were described to occur at 6 to 10 weeks after initiation of ICIs. 3,4 The recommended treatment of hypothyroidism associated with ICIs is the replacement of thyroid hormone via levothyroxine administration.…”

Section: Introductionmentioning

confidence: 99%

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Outcomes and Management of Immune Checkpoint Inhibitor–Induced Hypothyroidism: A Retrospective Analysis

Phillips

Reeves

2022

Ann Pharmacother

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Background: Immune checkpoint inhibitors (ICIs) used in cancer treatment cause immune-related adverse effects (irAEs), including thyroiditis leading to hypothyroidism. The management and outcomes of this irAE are not well established. Objective: The purpose of this analysis is to describe the onset, management, and outcomes of patients experiencing hypothyroidism from ICI. Methods: A retrospective study was conducted of adults receiving ICI therapy at a community cancer center between January 1, 2017, and February 1, 2020. The primary endpoint was to describe onset (timing) of hypothyroidism (thyroid-stimulating hormone [TSH] > 10 µIU/mL). Secondary outcomes included describing hypothyroidism symptoms and levothyroxine use, time to documented disease progression, and occurrence of additional adverse effects (AEs). Results: Of the 200 patients included in the study, 19% developed clinical hypothyroidism (TSH > 10 µIU/mL, or required initiation of or dose increase in levothyroxine). Median time to TSH higher than 10 µIU/mL was 13.3 weeks and symptoms of hypothyroidism occurred in 34% of patients developing clinical hypothyroidism. The median final daily levothyroxine dose was 88 mcg (0.88 mcg/kg). Time to disease progression was longer in those with clinical hypothyroidism (27.4 months vs. 6.8 months, respectively, P = .015). Additional AEs occurred in 68% of those developing hypothyroidism versus 49% without hypothyroidism ( P = .029). Conclusion and Relevance: Patients with clinical hypothyroidism during ICI treatment may have improved cancer outcomes, but they also are more likely to develop other AEs. Patients requiring thyroid replacement therapy with levothyroxine may benefit from a starting dose between 50 and 100 mcg/day, approximately 0.88 mcg/kg/day.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Outcomes and Management of Immune Checkpoint Inhibitor–Induced Hypothyroidism: A Retrospective Analysis

Phillips

Reeves

2022

Ann Pharmacother

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“…Although many studies have reported ICI-related endocrine toxicity, most of these data are derived from clinical trials (8,9), but there is short of data in real world.…”

Section: Introductionmentioning

confidence: 99%

A real-world retrospective study of incidence and associated factors of endocrine adverse events related to PD-1/PD-L1 inhibitors

Wang¹,

Hu²,

Zhang³

et al. 2023

Ann Transl Med

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Background: The adverse events (AEs) related to immune checkpoint inhibitors (ICIs) have been mostly described in clinical trials, however, such trials are restricted to selection criteria and the results cannot wholly represent the real-world setting. We aimed to evaluate the real-world endocrine AEs associated with programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) inhibitors in Chinese population. Methods: This retrospective study included cancer patients who were treated with PD-1/PD-L1 inhibitors between January 2018 and December 2020 at Xinqiao Hospital, the Third Military Medical University. The information of 581 patients was reviewed, and data on clinical characteristics, PD-1/PD-L1 use, occurrence of endocrine AEs, and response to PD-1 blockade treatment were collated. The definition of endocrine AEs relied on diagnostic tests. Fisher's exact test or Pearson's chi-squared test was used to analyze the associations between endocrine variables and several categorical variables. Multivariate analyses were performed using a logistic regression model.Results: Endocrine AEs were observed in 116 of the 581 patients (20.0%). The median time to onset of endocrine AEs was approximately 12 weeks. Pembrolizumab was associated with a significantly higher incidence of endocrine AEs compared to other anti-PD-1 agents (38.5%; P=0.0002); PD-1/PD-L1 inhibitor treatment combined with antiangiogenic therapy or with two other therapies (chemotherapy and antiangiogenic therapy) was associated with a significantly increased occurrence of endocrine AEs, compared to PD-1 blockade treatment alone (41.2%; P=0.015), both based on multivariate analysis. Patients who developed endocrine AEs had significantly higher overall response rates (ORRs; 33.3% vs. 23.1%, P=0.045) and disease control rates (DCRs; 91.1% vs. 79.1%, P=0.008) compared to patients without endocrine AEs.In multivariate analysis, endocrine AEs remained an independent factor for both ORR (OR: 1.764, 95%

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Endocrine Toxicities Related to Immunotherapy

Quinn

Carroll

Joshi

2022

Handbook of Cancer and Immunology

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Endocrine Toxicity and Outcomes in Patients With Metastatic Malignancies Treated With Immune Checkpoint Inhibitors

Cited by 14 publications

References 41 publications

Outcomes and Management of Immune Checkpoint Inhibitor–Induced Hypothyroidism: A Retrospective Analysis

Outcomes and Management of Immune Checkpoint Inhibitor–Induced Hypothyroidism: A Retrospective Analysis

A real-world retrospective study of incidence and associated factors of endocrine adverse events related to PD-1/PD-L1 inhibitors

Endocrine Toxicities Related to Immunotherapy

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