Circulating Tumor DNA Early Kinetics Predict Response of Metastatic Melanoma to Anti-PD1 Immunotherapy: Validation Study
The ability of early (first weeks of treatment) ctDNA kinetics to identify primary resistance to anti-PD1 immunotherapies was evaluated with a validation cohort of 49 patients treated with anti-PD1 for metastatic BRAF or NRAS-mutated melanoma, alone and pooled with the 53 patients from a previously...
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| Veröffentlicht in: | Cancers 2021-04, Vol.13 (8), p.1826 |
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| creator | Herbreteau, Guillaume Vallée, Audrey Knol, Anne-Chantal Théoleyre, Sandrine Quéreux, Gaëlle Varey, Emilie Khammari, Amir Dréno, Brigitte Denis, Marc G |
| description | The ability of early (first weeks of treatment) ctDNA kinetics to identify primary resistance to anti-PD1 immunotherapies was evaluated with a validation cohort of 49 patients treated with anti-PD1 for metastatic BRAF or NRAS-mutated melanoma, alone and pooled with the 53 patients from a previously described derivation cohort. BRAF or NRAS mutations were quantified on plasma DNA by digital PCR at baseline and after two or four weeks of treatment. ctDNA kinetics were interpreted according to pre-established biological response criteria. A biological progression (bP, i.e., a significant increase in ctDNA levels) at week two or week four was associated with a lack of benefit from anti-PD1 (4-month PFS = 0%; 1-year OS = 13%;
= 12/102). Patients without initial bP had significantly better PFS and OS (4-month PFS = 78%; 1-year OS = 73%;
= 26/102), as did patients whose ctDNA kinetics were not evaluable, due to low/undetectable baseline ctDNA (4-month PFS = 80%; 1-year OS = 81%;
= 64/102). ctDNA detection at first-line anti-PD1 initiation was an independent prognostic factor for OS and PFS in multivariate analysis. Overall, early ctDNA quantitative monitoring may allow the detection of primary resistances of metastatic melanoma to anti-PD1 immunotherapies. |
| doi_str_mv | 10.3390/cancers13081826 |
| format | Article |
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= 12/102). Patients without initial bP had significantly better PFS and OS (4-month PFS = 78%; 1-year OS = 73%;
= 26/102), as did patients whose ctDNA kinetics were not evaluable, due to low/undetectable baseline ctDNA (4-month PFS = 80%; 1-year OS = 81%;
= 64/102). ctDNA detection at first-line anti-PD1 initiation was an independent prognostic factor for OS and PFS in multivariate analysis. Overall, early ctDNA quantitative monitoring may allow the detection of primary resistances of metastatic melanoma to anti-PD1 immunotherapies.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13081826</identifier><identifier>PMID: 33920470</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Accuracy ; Cancer ; Deoxyribonucleic acid ; DNA ; Immunology ; Immunotherapy ; Life Sciences ; Lymphatic system ; Melanoma ; Metastases ; Metastasis ; Multivariate analysis ; Mutation ; Patients ; PD-1 protein ; Plasma ; Survival ; Survival analysis ; Validation studies</subject><ispartof>Cancers, 2021-04, Vol.13 (8), p.1826</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-87992eccc747b63824edc491429f8295820eea3181f009ef691cf8cd271590ca3</citedby><cites>FETCH-LOGICAL-c458t-87992eccc747b63824edc491429f8295820eea3181f009ef691cf8cd271590ca3</cites><orcidid>0000-0001-5865-3248 ; 0000-0001-9328-8004 ; 0000-0001-5574-5825</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069589/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069589/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33920470$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-03347554$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Herbreteau, Guillaume</creatorcontrib><creatorcontrib>Vallée, Audrey</creatorcontrib><creatorcontrib>Knol, Anne-Chantal</creatorcontrib><creatorcontrib>Théoleyre, Sandrine</creatorcontrib><creatorcontrib>Quéreux, Gaëlle</creatorcontrib><creatorcontrib>Varey, Emilie</creatorcontrib><creatorcontrib>Khammari, Amir</creatorcontrib><creatorcontrib>Dréno, Brigitte</creatorcontrib><creatorcontrib>Denis, Marc G</creatorcontrib><title>Circulating Tumor DNA Early Kinetics Predict Response of Metastatic Melanoma to Anti-PD1 Immunotherapy: Validation Study</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>The ability of early (first weeks of treatment) ctDNA kinetics to identify primary resistance to anti-PD1 immunotherapies was evaluated with a validation cohort of 49 patients treated with anti-PD1 for metastatic BRAF or NRAS-mutated melanoma, alone and pooled with the 53 patients from a previously described derivation cohort. BRAF or NRAS mutations were quantified on plasma DNA by digital PCR at baseline and after two or four weeks of treatment. ctDNA kinetics were interpreted according to pre-established biological response criteria. A biological progression (bP, i.e., a significant increase in ctDNA levels) at week two or week four was associated with a lack of benefit from anti-PD1 (4-month PFS = 0%; 1-year OS = 13%;
= 12/102). Patients without initial bP had significantly better PFS and OS (4-month PFS = 78%; 1-year OS = 73%;
= 26/102), as did patients whose ctDNA kinetics were not evaluable, due to low/undetectable baseline ctDNA (4-month PFS = 80%; 1-year OS = 81%;
= 64/102). ctDNA detection at first-line anti-PD1 initiation was an independent prognostic factor for OS and PFS in multivariate analysis. Overall, early ctDNA quantitative monitoring may allow the detection of primary resistances of metastatic melanoma to anti-PD1 immunotherapies.</description><subject>Accuracy</subject><subject>Cancer</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Life Sciences</subject><subject>Lymphatic system</subject><subject>Melanoma</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Multivariate analysis</subject><subject>Mutation</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>Plasma</subject><subject>Survival</subject><subject>Survival analysis</subject><subject>Validation studies</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdks1vFCEYxonR2Kb27M2QePHgtHwNHx5MNtvPuNVGq1dCGaZLMwNbYBr3v5dma9MuF96E3_O88PAC8B6jA0oVOrQmWJcypkhiSfgrsEuQIA3nir1-Vu-A_ZxvUV2UYsHFW7BT5QQxgXbB37lPdhpM8eEGXk1jTPDo-wwemzSs4TcfXPE2w8vkOm8L_OnyKobsYOzhhSsmlyq0tRxMiKOBJcJZKL65PMLwfBynEMvSJbNaf4F_zOC7SscAf5WpW78Db3ozZLf_uO-B3yfHV_OzZvHj9Hw-WzSWtbI0UihFnLVWMHHNqSTMdZYpzIjqJVGtJMg5Q7HEPULK9Vxh20vbEYFbhayhe-Drxnc1XY9V60JJZtCr5EeT1joar1-eBL_UN_FeS8SrvaoGnzcGyy3Z2WyhfQ0jjbomy0Tbsntc8U-P_VK8m1wuevTZuqEm5OKUNWkJkhwpQir6cQu9jVMKNY1KMcEJppxX6nBD2RRzTq5_ugRG-mEO9NYcVMWH509-4v__Ov0He9uveg</recordid><startdate>20210411</startdate><enddate>20210411</enddate><creator>Herbreteau, Guillaume</creator><creator>Vallée, Audrey</creator><creator>Knol, Anne-Chantal</creator><creator>Théoleyre, Sandrine</creator><creator>Quéreux, Gaëlle</creator><creator>Varey, Emilie</creator><creator>Khammari, Amir</creator><creator>Dréno, Brigitte</creator><creator>Denis, Marc G</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5865-3248</orcidid><orcidid>https://orcid.org/0000-0001-9328-8004</orcidid><orcidid>https://orcid.org/0000-0001-5574-5825</orcidid></search><sort><creationdate>20210411</creationdate><title>Circulating Tumor DNA Early Kinetics Predict Response of Metastatic Melanoma to Anti-PD1 Immunotherapy: Validation Study</title><author>Herbreteau, Guillaume ; 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BRAF or NRAS mutations were quantified on plasma DNA by digital PCR at baseline and after two or four weeks of treatment. ctDNA kinetics were interpreted according to pre-established biological response criteria. A biological progression (bP, i.e., a significant increase in ctDNA levels) at week two or week four was associated with a lack of benefit from anti-PD1 (4-month PFS = 0%; 1-year OS = 13%;
= 12/102). Patients without initial bP had significantly better PFS and OS (4-month PFS = 78%; 1-year OS = 73%;
= 26/102), as did patients whose ctDNA kinetics were not evaluable, due to low/undetectable baseline ctDNA (4-month PFS = 80%; 1-year OS = 81%;
= 64/102). ctDNA detection at first-line anti-PD1 initiation was an independent prognostic factor for OS and PFS in multivariate analysis. Overall, early ctDNA quantitative monitoring may allow the detection of primary resistances of metastatic melanoma to anti-PD1 immunotherapies.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33920470</pmid><doi>10.3390/cancers13081826</doi><orcidid>https://orcid.org/0000-0001-5865-3248</orcidid><orcidid>https://orcid.org/0000-0001-9328-8004</orcidid><orcidid>https://orcid.org/0000-0001-5574-5825</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Accuracy Cancer Deoxyribonucleic acid DNA Immunology Immunotherapy Life Sciences Lymphatic system Melanoma Metastases Metastasis Multivariate analysis Mutation Patients PD-1 protein Plasma Survival Survival analysis Validation studies |
| title | Circulating Tumor DNA Early Kinetics Predict Response of Metastatic Melanoma to Anti-PD1 Immunotherapy: Validation Study |
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