Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The optimal duration of PD-1 antibodies for metastatic melanoma is unknown. In previous trials, there has been the potential to cease therapy if the patient achieves a complete response (CR). We aimed to assess the outcomes of patients who had ceased anti-PD-1 antibodies in this setting. A retrospective review was carried out of CR to PD-1-based therapy across two institutions. Patients were from the Pembrolizumab Named Patient Program (PEM NPP), Nivolumab monotherapy (NIVO), and reimbursed Pembrolizumab (r PEM). Patients had to have experienced a CR to PD-1-based therapy and ceased therapy because of this. Disease recurrence was the primary outcome measured. Twenty-nine patients (PEM NPP, N=20; Nivo, N=3; r PEM, N=6) ceased anti-PD-1 therapy after CR for observation. The median age was 64 (27-83) years. All patients had treatment discontinued for observation. The median time to CR was 10.5 months in the PEM NPP, 7.5 months on r PEM groups, and 17 months in the NIVO group. The median time off therapy in PEM NPP was 10 months, NIVO was 9 months, and r PEM was 4.5 months. To date, three patients have shown a relapse at a median follow-up off treatment of 8 months. This is the first report of patients who have intentionally ceased PD-1-based therapy because of CR. With a follow-up of 8 months off treatment, the risk of relapse was low. Data such as these are clinically relevant as we need to be able to discuss cessation of therapy and relevant from a pharmacoeconomic perspective, given the cost of PD-1 antibodies to society.
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PMID:The cessation of anti-PD-1 antibodies of complete responders in metastatic melanoma. 2809 69

Cancer immunotherapy has emerged as treatment of multiple advanced cancer types. Immune checkpoint inhibitors, namely anticytotoxic T-lymphocyte antigen-4 (CTLA-4), antiprogrammed cell death-1 (PD-1), and antiprogrammed cell death-1 ligand 1 (PD-L1) antibodies, have been used for treatment of various cancers. Classified as immune-related adverse events, several endocrinopathies, including hypophysitis, are associated with these agents. Although anti-CTLA-4-induced hypophysitis has been frequently observed, hypophysitis upon use of anti-PD-1 and anti-PD-L1 antibodies is rare. Case 1 is a 65-year-old man presented with a stage IV non-small cell lung cancer (NSCLC) treated with atezolizumab (an anti-PD-L1 antibody) following several inefficacious chemotherapies. After 56 weeks of the treatment, he complained of general malaise and appetite loss, and was diagnosed with adrenal insufficiency. Endocrinological examination revealed isolated adrenocorticotropic hormone (ACTH) deficiency; pituitary magnetic resonance imaging (MRI) showed anterior pituitary atrophy. Hydrocortisone replacement therapy rapidly improved his symptoms and enabled him to continue atezolizumab therapy. Case 2 is a 70-year-old man with a stage IV NSCLC treated with atezolizumab. After 52 weeks of treatment, he was diagnosed with isolated ACTH deficiency. Pituitary MRI revealed no obvious abnormalities in the anterior pituitary. Hydrocortisone replacement therapy was also efficacious. We report two cases of atezolizumab-induced hypophysitis. Both showed isolated ACTH deficiency, suggesting similar clinical characteristics of hypophysitis associated with the use of anti-PD-1 antibodies. These results suggest a caution for the late-onset central adrenal insufficiency associated with hypophysitis in patients treated with anti-PD-L1 antibodies.
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PMID:Two Cases of Atezolizumab-Induced Hypophysitis. 2936 27

Hypophysitis is a frequent toxic endocrine side-effect of immunotherapy. Prevalence is higher with anti-CTLA-4 antibodies (4-20%) or in association with PD-1 inhibitors (8%). Diagnosis is presumptive, based on poorly specific clinical symptoms (usually, headache and asthenia) and/or hyponatremia and/or at least one pituitary deficit and/or abnormal imaging. Visual disorder or polyuropolydipsic syndrome are exceptional. In decreasing order of frequency, deficits are thyrotropic (86-100%), gonadotropic (85-100%) or corticotropic (50-73%); somatotropin deficit or abnormal prolactin level are rarer. Pituitary MRI in acute phase shows variable moderate increase in pituitary volume, ruling out differential diagnoses, especially pituitary metastasis. Treatment of corticotropin deficiency requires systematic emergency replacement therapy, with the usual modalities, while treatment of other deficits depends on clinical status and progression. Thyrotropin and gonadotropin deficits usually recover, but corticotropin deficiency persists over the long term, requiring education and specialized endocrinologic follow-up. Onset of hypophysitis does not contraindicate continuation of immunotherapy and does not usually require high dose synthetic glucocorticoids.
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PMID:Expert opinion on pituitary complications in immunotherapy. 3012 25

One of the novel PD-1 antibodies/immune checkpoint inhibitors, nivolumab is reported to be associated with a wide range of immune-related adverse events (irAEs). We hereby report a case of isolated adrenocorticotropic hormone (ACTH) deficiency developing in a patient with squamous cell lung cancer (SCC) during nivolumab therapy.
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PMID:A case of nivolumab-induced isolated adrenocorticotropic hormone (ACTH) deficiency. 3074 Mar

Nivolumab exerts antitumor effects by inhibiting binding of PD-L1 to PD-1, and offers proven effectiveness in various disease areas, including cancers of the head and neck. The mechanisms of action lead nivolumab to induce immune-related adverse events (irAE). We report a case of pituitary-adrenal dysfunction to isolated adrenocorticotropic hormone (ACTH) deficiency as an irAE of nivolumab in a patient treated for head and neck cancer. This is the first report of an irAE of nivolumab in the field of head and neck squamous cell cancer. The patient was a man in his 50s with cancer of the tongue and hypopharynx that recurred after chemoradiotherapy, surgery and chemotherapy. After starting nivolumab, irAEs developed after 8 courses. The case was managed from the early stages in collaboration with the endocrinology department. Pituitary-adrenal hypofunction due to isolated ACTH deficiency was diagnosed on the basis of endocrine tests. The patient responded to hydrocortisone replacement therapy and has been able to continue treatment with nivolumab while continuing oral hydrocortisone. Although irAEs involving pituitary gland disorders are rare, these events can become life-threatening when severe. Early diagnosis and treatment are essential and require regular blood sampling and collaboration with specialists from an early stage.
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PMID:Pituitary-adrenal dysfunction caused by nivolumab for head and neck cancer. 3135 19

Secreting pituitary adenomas are tumors for which few treatment options are available, including surgical treatment and management of hormonal imbalance due to altered pituitary secretion. In case of inoperable relapse, radiotherapy or chemotherapeutic treatment can be considered; the effectiveness of these treatments, however, remains limited. In the immunotherapy era, it is necessary to select patients who can benefit from immunotherapeutic treatment. Mismatch repair deficiency is strongly associated with responsiveness to anti-PD-1 in other cancers and can be detected using immunohistochemistry for MLH1, MSH2, MHS6, and PMS2. In this case report, we report a case of rapid disease progression to pembrolizumab in a patient with a MMRd pituitary adrenocorticotropic hormone (ACTH)-secreting adenoma. For the best of our knowledge, we described for the first time, a poor efficacy of pembrolizumab in a patient with ACTH-secreting pituitary adenoma having mismatch repair deficiency probably caused by high levels of cortisol in this patient. Prospective study should be performed to assess the activity of immune checkpoint inhibitor alone or in association with temozolomide in this subsetting of pituitary adenomas.
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PMID:Rapid disease progression in patient with mismatch-repair deficiency pituitary ACTH-secreting adenoma treated with checkpoint inhibitor pembrolizumab. 3170 99