Clinical characteristics of adrenal insufficiency as an immune-related adverse event in non-small-cell lung cancer

Ida, Hanae; Goto, Yasushi; Sato, Jun; Kanda, Shintaro; Shinno, Yuki; Morita, Ryou; Murakami, Shuji; Yoshida, Tatsuya; Horinouchi, Hidehito; Fujiwara, Yutaka; Yamamoto, Noboru; Fukuda, Takahiro; Ohashi, Ken; Ohe, Yuichiro

doi:10.1007/s12032-020-01357-x

Cited by 12 publications

(13 citation statements)

References 31 publications

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“…It is unclear whether the incidence of adrenal insufficiency increased the risk of the development of other irAEs. However, considering a previous report [10] and that this case involved three other irAEs, other irAEs may be a risk factor for the incidence of adrenal insufficiency. A previous phase I trial of patients treated with anti-PD-1 antibodies indicated that high doses of hydrocortisone (3–10 mg/kg) are used to treat adrenal insufficiency [12].…”

Section: Discussionmentioning

confidence: 75%

“…Adrenal insufficiency is a rare adverse event induced by anti-PD-1 antibodies [9]. A previous study reported that the median time for the development of adrenal insufficiency is 5.9 months (range 3.2–12.6) and 4 of 10 patients experience another irAE [10]. The latest-onset adrenal insufficiency in a previous case report occurred at 15 months [11].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the development of irAEs is a predictive factor for response to nivolumab (odds ratio: 0.11, p < 0.001). Ida et al [10] reported that the median overall survival (OS) of their patients with adrenal insufficiency was favorable at 15.4 months; thus, it may be possible to continue ICI treatment with a corticosteroid. A previous study reported that the median OS in an ICI interruption group owing to irAEs was significantly shorter than that in an ICI continuation group (8.3 vs. 14.5 months, p = 0.008) [14].…”

Section: Discussionmentioning

confidence: 99%

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A Case of Lung Adenocarcinoma with Long-Term Response after Late-Onset Pembrolizumab-Induced Acute Adrenal Insufficiency

Sonehara¹,

Tateishi²,

Hirabayashi³

et al. 2021

Case Rep Oncol

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Pembrolizumab is an anti-programmed cell death protein-1 antibody that is mainly used for the treatment of non-small cell lung cancer (NSCLC). Immune-related adverse events can be caused by immune checkpoint inhibitors; however, few case reports evaluate the prognosis of patients with NSCLC with late-onset immune-related adverse events. In this case, a 63-year-old man with stage IVA lung adenocarcinoma received pembrolizumab as first-line therapy and achieved a complete response. The patient developed hypothyroidism and skin toxicity owing to pembrolizumab over the course of treatment; however, the patient continued with pembrolizumab. The patient discontinued pembrolizumab after 20 cycles owing to appetite loss from 14 months after the initiation of pembrolizumab. Two months later, the symptoms worsened and the patient was taken to hospital by an ambulance owing to movement difficulty. The patient was diagnosed with acute adrenal insufficiency by endocrinological examinations. The condition of the patient improved after hydrocortisone treatment. Sixteen months have passed without the readministration of pembrolizumab and no recurrence of lung adenocarcinoma has been observed. Late-onset, severe, and diverse immune-related adverse events may be a favorable prognostic factor associated with survival.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A Case of Lung Adenocarcinoma with Long-Term Response after Late-Onset Pembrolizumab-Induced Acute Adrenal Insufficiency

Sonehara¹,

Tateishi²,

Hirabayashi³

et al. 2021

Case Rep Oncol

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“…In 1 retrospective study, 6 of the 10 patients who developed AI were male. The median age of patients with AI was 66 years, and median time of the onset of AI was 5.6 months [ 5 ]. The Japanese adverse drug event report database demonstrated the median time of the onset of nivolumab- and pembrolizumab-induced AI to be 156 and 118 days, respectively [ 6 ].…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…The dose of the bioactive hydrocortisone was insufficient to interfere with the effect of ICI. Ida et al [ 5 ] reported that the median OS in pretreated NSCLC patients while continuing ICIs after the development of AI was 15.4 months, and survival was favorable. Further studies are needed to evaluate the association between steroid dose and the efficacy of ICIs.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Pembrolizumab-Induced Adrenal Insufficiency in Patients with Untreated Advanced Non-Small Cell Lung Cancer: A Case Series

et al. 2021

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Pembrolizumab-induced adrenal insufficiency (AI) is recognized as a rare immune-related adverse event (irAE) that can be fatal if diagnosis is delayed. Clinical features of AI in patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab as the first-line treatment were observed. Five out of 49 patients with untreated advanced NSCLC developed AI between April 2017 and February 2021. Of the 5 patients, 4 developed AI with a grade >3 and were hospitalized. The median time of the onset of AI from the start of first-line treatment was 4.63 months. All the patients improved after corticosteroid replacement therapy. The efficacy of treatment was complete response in 1 patient and partial response in 4 patients. Median progression-free survival was 37.7 months, and overall survival had not been reached. This case series revealed the efficacy of immunotherapy in AI as an irAE.

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Incidence and risk factors of immune‐related adverse events induced by immune checkpoint inhibitors among older adults with non‐small cell lung cancer

Rong,

Bentley,

Bhattacharya

et al. 2024

Cancer Medicine

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BackgroundImmune checkpoint inhibitor (ICI) treatment has been linked to a variety of immune‐related adverse events (irAEs), which can affect any organ system. The incidence and risk factors of irAEs have not been adequately evaluated among older adults with NSCLC.MethodsA cohort study was conducted using 1999–2019 SEER‐Medicare data among beneficiaries aged ≥65 years with a diagnosis of NSCLC who received nivolumab, pembrolizumab, or atezolizumab. Incident irAEs were identified post‐ICI initiation. Demographic, cancer‐related characteristics, and clinical history risk factors of irAEs were evaluated with competing events considered.ResultsA total of 8175 older NSCLC patients were included (with 46.8% experiencing irAEs). Pneumonitis (16.5%), hypothyroidism (10.5%), arrhythmia (11.18%), and acute kidney injury (AKI) (5.8%) were the most common irAEs. The median time to first irAE was 82 days (IQR: 29–182 days). The earliest onset of irAE occurrence was for hematologic irAEs, while the latest were gastrointestinal, dermatologic, and musculoskeletal irAEs. Fine–Gray regression modeling revealed significantly greater hazards of irAE occurrence in patients who received pembrolizumab at index, did not have CNS metastases, had a history of autoimmune disorder, and had chemotherapy in combination with ICI. Race, socioeconomic status, previous radiation therapy, and comorbidity burden were found to be associated with the occurrence of certain type of irAEs.ConclusionA significant proportion of older patients with NSCLC develop an irAE after receiving ICI treatment. Factors related to cancer and treatment as well as demographics contribute to the increased risk of irAEs. Close monitoring and prediction of irAE among older patients receiving ICI is warranted.

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Clinical characteristics of adrenal insufficiency as an immune-related adverse event in non-small-cell lung cancer

Cited by 12 publications

References 31 publications

A Case of Lung Adenocarcinoma with Long-Term Response after Late-Onset Pembrolizumab-Induced Acute Adrenal Insufficiency

A Case of Lung Adenocarcinoma with Long-Term Response after Late-Onset Pembrolizumab-Induced Acute Adrenal Insufficiency

Pembrolizumab-Induced Adrenal Insufficiency in Patients with Untreated Advanced Non-Small Cell Lung Cancer: A Case Series

Incidence and risk factors of immune‐related adverse events induced by immune checkpoint inhibitors among older adults with non‐small cell lung cancer

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