Cautious addition of targeted therapy to PD-1 inhibitors after initial progression of BRAF mutant metastatic melanoma on checkpoint inhibitor therapy

Abstract Background Virtually all metastatic patients with metastatic melanoma who progress after initial treatment with PD-1 or CTLA-4 directed antibodies will die of their disease. Salvage options are urgently needed. It is theoretically attractive to combine immunotherapy with targeted agents in...

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Autores principales:	Wolfram Samlowski, Camille Adajar
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Checkpoint inhibitor Ipilimumab Nivolumab Pembrolizumab BRAF inhibitor MEK inhibitor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ca3ffe118c9142de8823f3a8fb1082a6
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spelling	oai:doaj.org-article:ca3ffe118c9142de8823f3a8fb1082a62021-11-14T12:30:37ZCautious addition of targeted therapy to PD-1 inhibitors after initial progression of BRAF mutant metastatic melanoma on checkpoint inhibitor therapy10.1186/s12885-021-08906-11471-2407https://doaj.org/article/ca3ffe118c9142de8823f3a8fb1082a62021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08906-1https://doaj.org/toc/1471-2407Abstract Background Virtually all metastatic patients with metastatic melanoma who progress after initial treatment with PD-1 or CTLA-4 directed antibodies will die of their disease. Salvage options are urgently needed. It is theoretically attractive to combine immunotherapy with targeted agents in progressing patients with BRAF mutation positive melanoma, but the toxicity of combined treatment has proven challenging. Methods We performed a retrospective analysis of our patient database and identified 23 patients who progressed on initial checkpoint inhibitor treatment, who subsequently had cautious addition of BRAF±MEK inhibitor therapy to continued PD-1 antibody treatment. Results We found an objective response rate of 55% in second line therapy, with a median progression-free survival of 33.4 months and median overall survival of 34.1 months, with 40% of patients in unmaintained remission at over 3 years. Ten of 12 responding patients were able to discontinue all therapy and continue in unmaintained remission. Toxicity of this approach was generally manageable (21.7% grade 3–5 toxicity). There was 1 early sudden death for unknown reasons in a responding patient. Discussion Our results suggest that 2nd line therapy with PD-1 inhibitors plus BRAF±MEK inhibitors has substantial activity and manageable toxicity. This treatment can induce additional durable complete responses in patients who have progressed on initial immunotherapy. These results suggest further evaluation be performed of sequential PD-1 antibody treatment with cautious addition of targeted therapy in appropriate patients.Wolfram SamlowskiCamille AdajarBMCarticleCheckpoint inhibitorIpilimumabNivolumabPembrolizumabBRAF inhibitorMEK inhibitorNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Checkpoint inhibitor Ipilimumab Nivolumab Pembrolizumab BRAF inhibitor MEK inhibitor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Checkpoint inhibitor Ipilimumab Nivolumab Pembrolizumab BRAF inhibitor MEK inhibitor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Wolfram Samlowski Camille Adajar Cautious addition of targeted therapy to PD-1 inhibitors after initial progression of BRAF mutant metastatic melanoma on checkpoint inhibitor therapy
description	Abstract Background Virtually all metastatic patients with metastatic melanoma who progress after initial treatment with PD-1 or CTLA-4 directed antibodies will die of their disease. Salvage options are urgently needed. It is theoretically attractive to combine immunotherapy with targeted agents in progressing patients with BRAF mutation positive melanoma, but the toxicity of combined treatment has proven challenging. Methods We performed a retrospective analysis of our patient database and identified 23 patients who progressed on initial checkpoint inhibitor treatment, who subsequently had cautious addition of BRAF±MEK inhibitor therapy to continued PD-1 antibody treatment. Results We found an objective response rate of 55% in second line therapy, with a median progression-free survival of 33.4 months and median overall survival of 34.1 months, with 40% of patients in unmaintained remission at over 3 years. Ten of 12 responding patients were able to discontinue all therapy and continue in unmaintained remission. Toxicity of this approach was generally manageable (21.7% grade 3–5 toxicity). There was 1 early sudden death for unknown reasons in a responding patient. Discussion Our results suggest that 2nd line therapy with PD-1 inhibitors plus BRAF±MEK inhibitors has substantial activity and manageable toxicity. This treatment can induce additional durable complete responses in patients who have progressed on initial immunotherapy. These results suggest further evaluation be performed of sequential PD-1 antibody treatment with cautious addition of targeted therapy in appropriate patients.
format	article
author	Wolfram Samlowski Camille Adajar
author_facet	Wolfram Samlowski Camille Adajar
author_sort	Wolfram Samlowski
title	Cautious addition of targeted therapy to PD-1 inhibitors after initial progression of BRAF mutant metastatic melanoma on checkpoint inhibitor therapy
title_short	Cautious addition of targeted therapy to PD-1 inhibitors after initial progression of BRAF mutant metastatic melanoma on checkpoint inhibitor therapy
title_full	Cautious addition of targeted therapy to PD-1 inhibitors after initial progression of BRAF mutant metastatic melanoma on checkpoint inhibitor therapy
title_fullStr	Cautious addition of targeted therapy to PD-1 inhibitors after initial progression of BRAF mutant metastatic melanoma on checkpoint inhibitor therapy
title_full_unstemmed	Cautious addition of targeted therapy to PD-1 inhibitors after initial progression of BRAF mutant metastatic melanoma on checkpoint inhibitor therapy
title_sort	cautious addition of targeted therapy to pd-1 inhibitors after initial progression of braf mutant metastatic melanoma on checkpoint inhibitor therapy
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ca3ffe118c9142de8823f3a8fb1082a6
work_keys_str_mv	AT wolframsamlowski cautiousadditionoftargetedtherapytopd1inhibitorsafterinitialprogressionofbrafmutantmetastaticmelanomaoncheckpointinhibitortherapy AT camilleadajar cautiousadditionoftargetedtherapytopd1inhibitorsafterinitialprogressionofbrafmutantmetastaticmelanomaoncheckpointinhibitortherapy
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Cautious addition of targeted therapy to PD-1 inhibitors after initial progression of BRAF mutant metastatic melanoma on checkpoint inhibitor therapy

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