Phase II Clinical Trial of Pembrolizumab in Patients with Progressive Metastatic Pheochromocytomas and Paragangliomas
| Autor: | Mingxuan Xu, Abdualrazzak Zarifa, Bettzy Stephen, Camilo Jimenez, Aung Naing, Apostolia Maria Tsimberidou, Vivek Subbiah, Jordi Rodon Anhert, Junsheng Ma, Mouhammed Amir Habra, Denái R. Milton, Fechukwu Akhmedzhanov, Siqing Fu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Disease Response 030209 endocrinology & metabolism Pembrolizumab lcsh:RC254-282 Article 03 medical and health sciences PD-1 inhibition 0302 clinical medicine Internal medicine medicine Clinical endpoint Endocrine system Progression-free survival metastatic pheochromocytoma Adverse effect business.industry lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Primary tumor Clinical trial pseudohypoxia 030220 oncology & carcinogenesis metastatic paraganglioma pembrolizumab business |
| Zdroj: | Cancers, Vol 12, Iss 2307, p 2307 (2020) Cancers Volume 12 Issue 8 |
| ISSN: | 2072-6694 |
| Popis: | 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&ndash 74%) achieved the primary endpoint. The objective response rate was 9% (95% CI: 0&ndash 41%). The clinical benefit rate was 73% (95% CI: 39&ndash 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&mdash not reached). The median survival duration was 19 months (95% CI: 9.9&mdash 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&rsquo hereditary backgrounds, tumor hormonal status, and the presence of infiltrating mononuclear inflammatory cells or PDL-1 expression in the primary tumor. |
| Databáze: | OpenAIRE |
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