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Phase II Clinical Trial of Pembrolizumab in Patients with Progressive Metastatic Pheochromocytomas and Paragangliomas

1
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2
Department of Investigational Cancer Therapeutics; The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
3
Department of Biostatistics; The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(8), 2307; https://doi.org/10.3390/cancers12082307
Received: 9 July 2020 / Revised: 7 August 2020 / Accepted: 14 August 2020 / Published: 16 August 2020
(This article belongs to the Section Clinical Trials of Cancer)
Metastatic pheochromocytomas and paragangliomas (MPPGs) are rare endocrine malignancies that are associated with high rates of morbidity and mortality because of their large tumor burden and location, progression, and release of catecholamines. Systemic therapies for MPPGs are limited. MPPGs are characterized by pseudohypoxia that may prevent immune system recognition. We conducted a phase II clinical trial of pembrolizumab in patients with progressive MPPGs. The primary endpoint was the non-progression rate at 27 weeks. The secondary endpoints included the objective response and clinical benefit rates, progression free and overall survival duration, and safety. We also determined whether PDL-1 expression and the presence of infiltrating mononuclear inflammatory cells in the primary tumor were associated with clinical response and hereditary background. Eleven patients were included in this trial, four (36%) with germline mutations and seven (64%) with hormonally active tumors. Four patients (40%, 95% confidence interval (CI) 12–74%) achieved the primary endpoint. The objective response rate was 9% (95% CI: 0–41%). The clinical benefit rate was 73% (95% CI: 39–94%). Four patients had grade 3 adverse events related to pembrolizumab. No patients experienced grade 4 or 5 adverse events or a catecholamine crisis. Progression free survival time was 5.7 months (95% CI: 4.37—not reached). The median survival duration was 19 months (95% CI: 9.9—not reached). PDL-1 expression and the presence of infiltrating mononuclear inflammatory cells in the primary tumor did not seem to be associated with disease response. Single-agent pembrolizumab has modest treatment efficacy in patients with progressive MPPGs. Positive responses seemed to be independent of patients’ hereditary backgrounds, tumor hormonal status, and the presence of infiltrating mononuclear inflammatory cells or PDL-1 expression in the primary tumor. View Full-Text
Keywords: PD-1 inhibition; pembrolizumab; metastatic pheochromocytoma; metastatic paraganglioma; pseudohypoxia PD-1 inhibition; pembrolizumab; metastatic pheochromocytoma; metastatic paraganglioma; pseudohypoxia
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Jimenez, C.; Subbiah, V.; Stephen, B.; Ma, J.; Milton, D.; Xu, M.; Zarifa, A.; Akhmedzhanov, F.O.; Tsimberidou, A.; Habra, M.A.; Rodon Anhert, J.; Fu, S.; Naing, A. Phase II Clinical Trial of Pembrolizumab in Patients with Progressive Metastatic Pheochromocytomas and Paragangliomas. Cancers 2020, 12, 2307.

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