Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study
Pituitary carcinoma is an aggressive tumor characterized by metastatic spread beyond the sellar region. Symptoms can be debilitating due to hormonal excess and survival is poor. Pituitary carcinomas recur despite conventional multimodality treatments. Given the recent advances in the use of immune c...
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| Format: | Article |
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001532.full |
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| author | Siqing Fu Aung Naing Filip Janku Mingxuan Xu Anas Alshawa Nazanin Majd Steven G Waguespack Marta Penas-Prado Carlos Kamiya-Matsuoka Shaan M Raza Ian E McCutcheon |
| author_facet | Siqing Fu Aung Naing Filip Janku Mingxuan Xu Anas Alshawa Nazanin Majd Steven G Waguespack Marta Penas-Prado Carlos Kamiya-Matsuoka Shaan M Raza Ian E McCutcheon |
| author_sort | Siqing Fu |
| collection | DOAJ |
| description | Pituitary carcinoma is an aggressive tumor characterized by metastatic spread beyond the sellar region. Symptoms can be debilitating due to hormonal excess and survival is poor. Pituitary carcinomas recur despite conventional multimodality treatments. Given the recent advances in the use of immune checkpoint inhibitors (CPIs) to treat various solid cancers, there has been interest in exploring the role of immunotherapy for treating aggressive, refractory pituitary tumors. We treated 4 patients with pituitary carcinoma with pembrolizumab as part of a phase II clinical trial. Two patients (patients 1 and 2) with functioning corticotroph pituitary carcinomas (refractory to surgery, radiotherapy and chemotherapy) had partial radiographic (60% and 32% per Immune-Related Response Evaluation Criteria In Solid Tumors, respectively) and hormonal responses. Patient 1’s response continues 42 months after initiation of pembrolizumab and his tumor tissue obtained after treatment with temozolomide demonstrated a hypermutator phenotype with MSH2 and MSH6 gene mutations. Patient 2’s tumor after exposure to temozolomide was not sampled, but prior somatic mutational testing was negative. One patient with a non-functioning corticotroph tumor (patient 3) had a best response of stable disease for 4 months. One patient with a prolactin-secreting carcinoma (patient 4) had progressive disease. The latter 2 patients’ tumors did not demonstrate a hypermutator phenotype after treatment with temozolomide. Programmed death-ligand 1 staining was negative in all tumors. We report 2 cases of corticotroph pituitary carcinoma responsive to pembrolizumab after prior exposure to alkylating agents. The role of CPIs in treating patients with pituitary carcinoma, the relationship between tumor subtype and response to immunotherapy and mechanisms of hypermutation in this orphan disease require further study.Trial registration number: NCT02721732. |
| format | Article |
| id | doaj-art-e142b33dba1045f1b1ac27cad95671c1 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-e142b33dba1045f1b1ac27cad95671c12025-08-20T02:13:22ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001532Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II studySiqing Fu0Aung Naing1Filip Janku2Mingxuan Xu3Anas Alshawa4Nazanin Majd5Steven G Waguespack6Marta Penas-Prado7Carlos Kamiya-Matsuoka8Shaan M Raza9Ian E McCutcheon10Aff2 0000 0001 2291 4776grid.240145.6Department of Investigational Cancer TherapeuticsThe University of Texas MD Anderson Cancer Center 1515 Holcombe Blvd 77030 Houston TX USA14 Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA5 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, USAInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA1 Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA2 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA1 Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA1 Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA4 Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA4 Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAPituitary carcinoma is an aggressive tumor characterized by metastatic spread beyond the sellar region. Symptoms can be debilitating due to hormonal excess and survival is poor. Pituitary carcinomas recur despite conventional multimodality treatments. Given the recent advances in the use of immune checkpoint inhibitors (CPIs) to treat various solid cancers, there has been interest in exploring the role of immunotherapy for treating aggressive, refractory pituitary tumors. We treated 4 patients with pituitary carcinoma with pembrolizumab as part of a phase II clinical trial. Two patients (patients 1 and 2) with functioning corticotroph pituitary carcinomas (refractory to surgery, radiotherapy and chemotherapy) had partial radiographic (60% and 32% per Immune-Related Response Evaluation Criteria In Solid Tumors, respectively) and hormonal responses. Patient 1’s response continues 42 months after initiation of pembrolizumab and his tumor tissue obtained after treatment with temozolomide demonstrated a hypermutator phenotype with MSH2 and MSH6 gene mutations. Patient 2’s tumor after exposure to temozolomide was not sampled, but prior somatic mutational testing was negative. One patient with a non-functioning corticotroph tumor (patient 3) had a best response of stable disease for 4 months. One patient with a prolactin-secreting carcinoma (patient 4) had progressive disease. The latter 2 patients’ tumors did not demonstrate a hypermutator phenotype after treatment with temozolomide. Programmed death-ligand 1 staining was negative in all tumors. We report 2 cases of corticotroph pituitary carcinoma responsive to pembrolizumab after prior exposure to alkylating agents. The role of CPIs in treating patients with pituitary carcinoma, the relationship between tumor subtype and response to immunotherapy and mechanisms of hypermutation in this orphan disease require further study.Trial registration number: NCT02721732.https://jitc.bmj.com/content/8/2/e001532.full |
| spellingShingle | Siqing Fu Aung Naing Filip Janku Mingxuan Xu Anas Alshawa Nazanin Majd Steven G Waguespack Marta Penas-Prado Carlos Kamiya-Matsuoka Shaan M Raza Ian E McCutcheon Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study Journal for ImmunoTherapy of Cancer |
| title | Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study |
| title_full | Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study |
| title_fullStr | Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study |
| title_full_unstemmed | Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study |
| title_short | Efficacy of pembrolizumab in patients with pituitary carcinoma: report of four cases from a phase II study |
| title_sort | efficacy of pembrolizumab in patients with pituitary carcinoma report of four cases from a phase ii study |
| url | https://jitc.bmj.com/content/8/2/e001532.full |
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