Immune checkpoint inhibitor therapy for ACTH-secreting pituitary carcinoma: a new emerging treatment?

Sol, Bastiaan; Filette, Jeroen de; Awada, Gil; Raeymaeckers, Steven; Aspeslagh, Sandrine; Andreescu, Corina; Neyns, Bart; Velkeniers, Brigitte

doi:10.1530/eje-20-0151

Cited by 39 publications

(40 citation statements)

References 12 publications

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“…The rest of patients with unmet management of tumor progress still requires more effective treatment than TMZ (43). Nowadays, diversified innovative agents, including immune checkpoint inhibitors, VEGFR-targeted therapy, PI3K/AKT/mTOR inhibitors, and tyrosine kinase inhibitors, represent inspiring clinical benefit among those patients under TMZ alone or in combination therapy (7,44,45).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis

Luo¹,

Tan²,

Chen³

et al. 2021

Front. Neurol.

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Background: A growing number of evidences suggest that TMZ applications can generate impressive benefits for APT and PC patients. However, the definite role of TMZ for individuals remains unclarified due to the variation between studies. And the predictive factors to alter its efficacy remain debatable.Objective: To evaluate the long-term effectiveness and safety profile of TMZ in the treatment of pituitary malignancies, and delineate the predictors during its clinical employment.Results: A literature retrieval was conducted from online databases for studies published up to December 31, 2020. Twenty one studies involving 429 patients were identified. TMZ exhibited 41% radiological overall response rate (rORR). The biochemical response rate was determinate in 53% of the functioning subset. Two-year and 4-year survival rate were 79 and 61%, respectively. TMZ prolonged the median PFS and OS as 20.18 and 40.24 months. TMZ-related adverse events occurred in 19% of patients. Regarding predictors of TMZ response, rORR was dramatically improved in patients with low/intermediate MGMT expression than those with high-MGMT (>50%) (p < 0.001). The benefit of TMZ varied according to functioning subtype of patients, with greater antitumor activities in functioning subgroups and fewer activities in non-functioning sets (p < 0.001). Notably, the concomitant therapy of radiotherapy and TMZ significantly increased the rORR (p = 0.007).Conclusion: TMZ elicits clinical benefits with moderate adverse events in APT and PC patients. MGMT expression and clinical subtype of secreting function might be vital predictors of TMZ efficacy. In the future, the combination of radiotherapy with TMZ may further improve the clinical outcomes than TMZ monotherapy.

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Section: Discussionmentioning

confidence: 99%

“…Innovative strategies have been widely investigated to utmost reverse the malignant progression of PAs (7). Temozolomide (TMZ), an oral alkylating chemotherapeutic agent, has been established as first-line chemotherapy for high-grade gliomas and intracranial metastatic tumors (8).…”

Section: Introductionmentioning

confidence: 99%

Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis

Luo¹,

Tan²,

Chen³

et al. 2021

Front. Neurol.

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“…Firstly, there are a series of ongoing RCTs on both ICI-monotherapy and combination therapy that collectively involve more than 600 patients with solid tumours, including PHEO/PGLs. Secondly, even if it is presently impossible to draw any conclusion about the antitumoural activity of ipilimumab + nivolumab in PHEO/PGL based on the preliminary results so far available, very recent data suggest the potential benefits of such a combination of drugs in other NENs [48,49]. In addition to current trials on combination therapy, potential future studies employing ICIs in sequence, or as sandwich therapy, would be crucial to further define the role if ICIs in patients with aggressive PHEO/PGL.…”

Section: Discussionmentioning

confidence: 99%

Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks

Fanciulli

Molfetta

Dotto

et al. 2020

JCM

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Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respectively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progressive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology.

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“…Of these five cases, three cases were ACTH-producing carcinomas, one case was an ACTH-producing adenoma, and one case was a prolactinoma. All ACTH-producing carcinoma cases received a combination of IPI and NIV and showed decreased to stable sizes of pituitary carcinomas, ACTH levels, and the liver metastatic volume in two cases ( 29 , 30 , 94 ). However, one of these positively responding cases of pituitary carcinoma recurred over 1 year.…”

Section: Immunotherapymentioning

confidence: 99%

Multimodal Non-Surgical Treatments of Aggressive Pituitary Tumors

et al. 2021

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Up to 35% of aggressive pituitary tumors recur and significantly affect mortality and quality of life. Management can be challenging and often requires multimodal treatment. Current treatment options, including surgery, conventional medical therapies such as dopamine agonists, somatostatin receptor agonists and radiotherapy, often fail to inhibit pituitary tumor growth. Recently, anti-tumor effects of chemotherapeutic drugs such as Temozolomide, Capecitabine, and Everolimus, as well as peptide receptor radionuclide therapy on aggressive pituitary tumors have been increasingly investigated and yield mixed, although sometimes promising, outcomes. The purpose of this review is to provide thorough information on non-surgical medical therapies and their efficacies and used protocols for aggressive pituitary adenomas from pre-clinical level to clinical use.

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Immune checkpoint inhibitor therapy for ACTH-secreting pituitary carcinoma: a new emerging treatment?

Cited by 39 publications

References 12 publications

Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis

Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis

Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks

Multimodal Non-Surgical Treatments of Aggressive Pituitary Tumors

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