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Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?
Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.

checkpoint inhibitors, clinical trials, nasopharyngeal carcinoma
0020-7136
2305-2314
Masterson, Liam
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Howard, James
4cbe10c2-e6bf-42ec-9fa5-7e35b71ac2e6
Gonzalez-Cruz, Jazmina
85be2da7-c9c9-451d-b228-8e6f5f537634
Jackson, Christopher
80e41ba6-fe3d-4aac-a276-15d0d32410c3
Barnett, Catherine
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Overton, Lewis
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Liu, Howard
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Ladwa, Rahul
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Simpson, Fiona
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McGrath, Margie
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Wallwork, Ben
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Jones, Terry
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Ottensmeier, Christian
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Chua, Melvin L.K.
e788a167-6703-47ec-99bb-6d055e6a7c9a
Perry, Chris
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Khanna, Rajiv
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Panizza, Benedict
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Porceddu, Sandro
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Lechner, Matt
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Masterson, Liam
6c6cee63-03c7-4cea-8c69-2f2f77d3e50d
Howard, James
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Gonzalez-Cruz, Jazmina
85be2da7-c9c9-451d-b228-8e6f5f537634
Jackson, Christopher
80e41ba6-fe3d-4aac-a276-15d0d32410c3
Barnett, Catherine
58900931-5383-431a-8a6e-b79d05f81b65
Overton, Lewis
88e9d3f8-8604-4887-84c7-96d11709d8b3
Liu, Howard
d0c34138-b93f-497f-bfba-3e15d6a5165f
Ladwa, Rahul
3ecb251d-eba4-4635-bcfd-084b87535f5a
Simpson, Fiona
28301d1a-9068-4d43-82f6-1ef28f614f79
McGrath, Margie
b1056b86-1b41-493c-b7c4-65d08d1093ea
Wallwork, Ben
7e45f052-a91b-4830-9643-2a235332fd01
Jones, Terry
9d84f271-9bda-4a23-98a3-8a442f457d97
Ottensmeier, Christian
42b8a398-baac-4843-a3d6-056225675797
Chua, Melvin L.K.
e788a167-6703-47ec-99bb-6d055e6a7c9a
Perry, Chris
a3b75a4b-0508-4240-923c-b747fabd72df
Khanna, Rajiv
cce60f4d-3003-4258-8719-51c738489d3c
Panizza, Benedict
a05ae572-1d12-4a3b-ba17-97ea7b39a4d7
Porceddu, Sandro
74621a54-95be-44ba-836d-98f69b3b2921
Lechner, Matt
327faa2a-e083-46bb-8da6-337114f3a172

Masterson, Liam, Howard, James, Gonzalez-Cruz, Jazmina, Jackson, Christopher, Barnett, Catherine, Overton, Lewis, Liu, Howard, Ladwa, Rahul, Simpson, Fiona, McGrath, Margie, Wallwork, Ben, Jones, Terry, Ottensmeier, Christian, Chua, Melvin L.K., Perry, Chris, Khanna, Rajiv, Panizza, Benedict, Porceddu, Sandro and Lechner, Matt (2020) Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation? International Journal of Cancer, 146 (8), 2305-2314. (doi:10.1002/ijc.32869).

Record type: Article

Abstract

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.

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More information

Accepted/In Press date: 12 December 2019
e-pub ahead of print date: 17 January 2020
Published date: 15 April 2020
Keywords: checkpoint inhibitors, clinical trials, nasopharyngeal carcinoma

Identifiers

Local EPrints ID: 439767
URI: http://eprints.soton.ac.uk/id/eprint/439767
ISSN: 0020-7136
PURE UUID: 091be1eb-8cad-4062-ad3e-2bd1662c05c0

Catalogue record

Date deposited: 01 May 2020 16:40
Last modified: 25 Nov 2021 23:13

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Contributors

Author: Liam Masterson
Author: James Howard
Author: Jazmina Gonzalez-Cruz
Author: Christopher Jackson
Author: Catherine Barnett
Author: Lewis Overton
Author: Howard Liu
Author: Rahul Ladwa
Author: Fiona Simpson
Author: Margie McGrath
Author: Ben Wallwork
Author: Terry Jones
Author: Melvin L.K. Chua
Author: Chris Perry
Author: Rajiv Khanna
Author: Benedict Panizza
Author: Sandro Porceddu
Author: Matt Lechner

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