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Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whet...

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Autores principales: Bedrose, Sara, Miller, Kevin Charles, Altameemi, Lina, Ali, Mohamed S, Nassar, Sameh, Garg, Naveen, Daher, Marilyne, Eaton, Keith D, Yorio, Jeffrey Thomas, Daniel, Davey B, Campbell, Matthew, Bible, Keith C, Ryder, Mabel, Chintakuntlawar, Ashish V, Habra, Mouhammed Amir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394183/
https://www.ncbi.nlm.nih.gov/pubmed/32737143
http://dx.doi.org/10.1136/jitc-2020-001009
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author Bedrose, Sara
Miller, Kevin Charles
Altameemi, Lina
Ali, Mohamed S
Nassar, Sameh
Garg, Naveen
Daher, Marilyne
Eaton, Keith D
Yorio, Jeffrey Thomas
Daniel, Davey B
Campbell, Matthew
Bible, Keith C
Ryder, Mabel
Chintakuntlawar, Ashish V
Habra, Mouhammed Amir
author_facet Bedrose, Sara
Miller, Kevin Charles
Altameemi, Lina
Ali, Mohamed S
Nassar, Sameh
Garg, Naveen
Daher, Marilyne
Eaton, Keith D
Yorio, Jeffrey Thomas
Daniel, Davey B
Campbell, Matthew
Bible, Keith C
Ryder, Mabel
Chintakuntlawar, Ashish V
Habra, Mouhammed Amir
author_sort Bedrose, Sara
collection PubMed
description BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC. METHODS: A retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC. RESULTS: Eight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21–49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2–9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8–not reached) and median duration of therapy was 8.5 months (range 2–22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events. CONCLUSIONS: In our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.
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spelling pubmed-73941832020-08-11 Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma Bedrose, Sara Miller, Kevin Charles Altameemi, Lina Ali, Mohamed S Nassar, Sameh Garg, Naveen Daher, Marilyne Eaton, Keith D Yorio, Jeffrey Thomas Daniel, Davey B Campbell, Matthew Bible, Keith C Ryder, Mabel Chintakuntlawar, Ashish V Habra, Mouhammed Amir J Immunother Cancer Clinical/Translational Cancer Immunotherapy BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC. METHODS: A retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC. RESULTS: Eight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21–49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2–9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8–not reached) and median duration of therapy was 8.5 months (range 2–22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events. CONCLUSIONS: In our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response. BMJ Publishing Group 2020-07-30 /pmc/articles/PMC7394183/ /pubmed/32737143 http://dx.doi.org/10.1136/jitc-2020-001009 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Clinical/Translational Cancer Immunotherapy
Bedrose, Sara
Miller, Kevin Charles
Altameemi, Lina
Ali, Mohamed S
Nassar, Sameh
Garg, Naveen
Daher, Marilyne
Eaton, Keith D
Yorio, Jeffrey Thomas
Daniel, Davey B
Campbell, Matthew
Bible, Keith C
Ryder, Mabel
Chintakuntlawar, Ashish V
Habra, Mouhammed Amir
Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma
title Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma
title_full Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma
title_fullStr Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma
title_full_unstemmed Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma
title_short Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma
title_sort combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394183/
https://www.ncbi.nlm.nih.gov/pubmed/32737143
http://dx.doi.org/10.1136/jitc-2020-001009
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