Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update 2017.
Identifieur interne : 000330 ( Main/Exploration ); précédent : 000329; suivant : 000331Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update 2017.
Auteurs : Selma Ugurel [Allemagne] ; Joachim Röhmel [Allemagne] ; Paolo A. Ascierto [Italie] ; Keith T. Flaherty [États-Unis] ; Jean Jacques Grob [France] ; Axel Hauschild [Allemagne] ; James Larkin [Royaume-Uni] ; Georgina V. Long [Australie] ; Paul Lorigan [Royaume-Uni] ; Grant A. Mcarthur [Australie] ; Antoni Ribas [États-Unis] ; Caroline Robert [France] ; Dirk Schadendorf [Allemagne] ; Claus Garbe [Allemagne]Source :
- European journal of cancer (Oxford, England : 1990) [ 1879-0852 ] ; 2017.
Descripteurs français
- KwdFr :
- Anticorps monoclonaux (usage thérapeutique), Antinéoplasiques (usage thérapeutique), Essais cliniques comme sujet, Estimation de Kaplan-Meier, Humains, Immunothérapie (), Inhibiteurs de protéines kinases (usage thérapeutique), Médicaments en essais cliniques (usage thérapeutique), Mélanome (secondaire), Mélanome (traitement médicamenteux), Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique), Thérapie moléculaire ciblée (), Tumeurs cutanées (anatomopathologie), Tumeurs cutanées (traitement médicamenteux).
- MESH :
- anatomopathologie : Tumeurs cutanées.
- secondaire : Mélanome.
- traitement médicamenteux : Mélanome, Tumeurs cutanées.
- usage thérapeutique : Anticorps monoclonaux, Antinéoplasiques, Inhibiteurs de protéines kinases, Médicaments en essais cliniques, Protocoles de polychimiothérapie antinéoplasique.
- Essais cliniques comme sujet, Estimation de Kaplan-Meier, Humains, Immunothérapie, Thérapie moléculaire ciblée.
English descriptors
- KwdEn :
- Antibodies, Monoclonal (therapeutic use), Antineoplastic Agents (therapeutic use), Antineoplastic Combined Chemotherapy Protocols (therapeutic use), Clinical Trials as Topic, Drugs, Investigational (therapeutic use), Humans, Immunotherapy (methods), Kaplan-Meier Estimate, Melanoma (drug therapy), Melanoma (secondary), Molecular Targeted Therapy (methods), Protein Kinase Inhibitors (therapeutic use), Skin Neoplasms (drug therapy), Skin Neoplasms (pathology).
- MESH :
- chemical , therapeutic use : Antibodies, Monoclonal, Antineoplastic Agents, Drugs, Investigational, Protein Kinase Inhibitors.
- drug therapy : Melanoma, Skin Neoplasms.
- methods : Immunotherapy, Molecular Targeted Therapy.
- pathology : Skin Neoplasms.
- secondary : Melanoma.
- therapeutic use : Antineoplastic Combined Chemotherapy Protocols.
- Clinical Trials as Topic, Humans, Kaplan-Meier Estimate.
Abstract
The treatment of metastatic melanoma is still undergoing a process of major change. The two most important novel therapeutic strategies, selective kinase inhibitors and immune checkpoint blockers, both significantly prolong survival times of patients with advanced metastatic disease. Different agents, dose regimens and combinations have been tested against each other vigorously within these two groups. However, results from prospective head-to-head comparative studies of both strategies are still lacking. We performed an exploratory analysis of survival data from selected clinical trials representative for the new treatment strategies in advanced metastatic melanoma. Eighty-three Kaplan-Meier survival curves from 25 trials were digitised and grouped by therapeutic strategy and treatment line. For each of these groups, mean survival curves were generated for progression-free (PFS) and overall survival (OS) by weighted averaging. Survival curves grouped together by therapeutic strategy revealed a high concordance, particularly in the first-line setting. For kinase inhibitors, the most favourable PFS and OS in all therapy lines were observed for combined BRAF plus MEK inhibition. For immune checkpoint inhibitors, combined PD-1 plus CTLA-4 inhibition demonstrated the best survival outcome in all categories except for OS in first-line therapy. For the latter, combined PD-1 plus CTLA-4 inhibition showed similar outcomes as single-agent PD-1 inhibition. Comparison of kinase inhibitors and checkpoint blockers revealed a superiority of combined BRAF plus MEK inhibition within the first 6 months, later changing to a superiority of PD-1 blockers alone or in combination with CTLA-4 blockers. These results need confirmation by prospective clinical trials.
DOI: 10.1016/j.ejca.2017.06.028
PubMed: 28756137
Affiliations:
- Allemagne, Australie, France, Italie, Royaume-Uni, États-Unis
- Angleterre, Bade-Wurtemberg, Californie, District de Tübingen, Grand Londres, Grand Manchester, Massachusetts, Nouvelle-Galles du Sud, Provence-Alpes-Côte d'Azur, Schleswig-Holstein, Victoria (État)
- Kiel, Londres, Manchester, Marseille, Melbourne, Sydney, Tübingen
- Université de Manchester, Université de Melbourne, Université de Sydney
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Le document en format XML
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Electronic address: selma.ugurel@uk-essen.de.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea><wicri:noRegion>Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion></affiliation></author><author><name sortKey="Rohmel, Joachim" sort="Rohmel, Joachim" uniqKey="Rohmel J" first="Joachim" last="Röhmel">Joachim Röhmel</name><affiliation wicri:level="1"><nlm:affiliation>Bremen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Bremen</wicri:regionArea></affiliation></author><author><name sortKey="Ascierto, Paolo A" sort="Ascierto, Paolo A" uniqKey="Ascierto P" first="Paolo A" last="Ascierto">Paolo A. Ascierto</name><affiliation wicri:level="1"><nlm:affiliation>Melanoma, Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", Naples, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Melanoma, Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", Naples</wicri:regionArea><wicri:noRegion>Naples</wicri:noRegion></affiliation></author><author><name sortKey="Flaherty, Keith T" sort="Flaherty, Keith T" uniqKey="Flaherty K" first="Keith T" last="Flaherty">Keith T. Flaherty</name><affiliation wicri:level="2"><nlm:affiliation>Massachusetts General Hospital, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Massachusetts General Hospital, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Grob, Jean Jacques" sort="Grob, Jean Jacques" uniqKey="Grob J" first="Jean Jacques" last="Grob">Jean Jacques Grob</name><affiliation wicri:level="3"><nlm:affiliation>Department of Dermatology, Timone Hospital and Aix-Marseille University, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Dermatology, Timone Hospital and Aix-Marseille University, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Hauschild, Axel" sort="Hauschild, Axel" uniqKey="Hauschild A" first="Axel" last="Hauschild">Axel Hauschild</name><affiliation wicri:level="3"><nlm:affiliation>Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel</wicri:regionArea><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Larkin, James" sort="Larkin, James" uniqKey="Larkin J" first="James" last="Larkin">James Larkin</name><affiliation wicri:level="3"><nlm:affiliation>Royal Marsden Hospital NHS Foundation Trust, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Royal Marsden Hospital NHS Foundation Trust, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Long, Georgina V" sort="Long, Georgina V" uniqKey="Long G" first="Georgina V" last="Long">Georgina V. Long</name><affiliation wicri:level="4"><nlm:affiliation>Melanoma Institute Australia, The University of Sydney, and Royal North Shore Hospital, Sydney, NSW, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Melanoma Institute Australia, The University of Sydney, and Royal North Shore Hospital, Sydney, NSW</wicri:regionArea><orgName type="university">Université de Sydney</orgName><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Lorigan, Paul" sort="Lorigan, Paul" uniqKey="Lorigan P" first="Paul" last="Lorigan">Paul Lorigan</name><affiliation wicri:level="4"><nlm:affiliation>University of Manchester, The Christie NHS Foundation Trust, Manchester, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>University of Manchester, The Christie NHS Foundation Trust, Manchester</wicri:regionArea><placeName><settlement type="city">Manchester</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Manchester</region><settlement type="city">Manchester</settlement></placeName><orgName type="university">Université de Manchester</orgName></affiliation></author><author><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A" last="Mcarthur">Grant A. Mcarthur</name><affiliation wicri:level="4"><nlm:affiliation>Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia and University of Melbourne, Parkville, VIC, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia and University of Melbourne, Parkville, VIC</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Ribas, Antoni" sort="Ribas, Antoni" uniqKey="Ribas A" first="Antoni" last="Ribas">Antoni Ribas</name><affiliation wicri:level="2"><nlm:affiliation>University of California, Los Angeles, CA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>University of California, Los Angeles, CA</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Robert, Caroline" sort="Robert, Caroline" uniqKey="Robert C" first="Caroline" last="Robert">Caroline Robert</name><affiliation wicri:level="1"><nlm:affiliation>Gustave Roussy Cancer Campus, Villejuif Grand-Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Gustave Roussy Cancer Campus, Villejuif Grand-Paris</wicri:regionArea><wicri:noRegion>Villejuif Grand-Paris</wicri:noRegion><wicri:noRegion>Villejuif Grand-Paris</wicri:noRegion></affiliation></author><author><name sortKey="Schadendorf, Dirk" sort="Schadendorf, Dirk" uniqKey="Schadendorf D" first="Dirk" last="Schadendorf">Dirk Schadendorf</name><affiliation wicri:level="1"><nlm:affiliation>Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea><wicri:noRegion>Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion><wicri:noRegion>Essen</wicri:noRegion></affiliation></author><author><name sortKey="Garbe, Claus" sort="Garbe, Claus" uniqKey="Garbe C" first="Claus" last="Garbe">Claus Garbe</name><affiliation wicri:level="3"><nlm:affiliation>Center for Dermatooncology, Department of Dermatology, University of Tuebingen, Tuebingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Center for Dermatooncology, Department of Dermatology, University of Tuebingen, Tuebingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author></analytic><series><title level="j">European journal of cancer (Oxford, England : 1990)</title><idno type="eISSN">1879-0852</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Monoclonal (therapeutic use)</term><term>Antineoplastic Agents (therapeutic use)</term><term>Antineoplastic Combined Chemotherapy Protocols (therapeutic use)</term><term>Clinical Trials as Topic</term><term>Drugs, Investigational (therapeutic use)</term><term>Humans</term><term>Immunotherapy (methods)</term><term>Kaplan-Meier Estimate</term><term>Melanoma (drug therapy)</term><term>Melanoma (secondary)</term><term>Molecular Targeted Therapy (methods)</term><term>Protein Kinase Inhibitors (therapeutic use)</term><term>Skin Neoplasms (drug therapy)</term><term>Skin Neoplasms (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Anticorps monoclonaux (usage thérapeutique)</term><term>Antinéoplasiques (usage thérapeutique)</term><term>Essais cliniques comme sujet</term><term>Estimation de Kaplan-Meier</term><term>Humains</term><term>Immunothérapie ()</term><term>Inhibiteurs de protéines kinases (usage thérapeutique)</term><term>Médicaments en essais cliniques (usage thérapeutique)</term><term>Mélanome (secondaire)</term><term>Mélanome (traitement médicamenteux)</term><term>Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique)</term><term>Thérapie moléculaire ciblée ()</term><term>Tumeurs cutanées (anatomopathologie)</term><term>Tumeurs cutanées (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antineoplastic Agents</term><term>Drugs, Investigational</term><term>Protein Kinase Inhibitors</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs cutanées</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Melanoma</term><term>Skin Neoplasms</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Immunotherapy</term><term>Molecular Targeted Therapy</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Skin Neoplasms</term></keywords><keywords scheme="MESH" qualifier="secondaire" xml:lang="fr"><term>Mélanome</term></keywords><keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Melanoma</term></keywords><keywords scheme="MESH" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Combined Chemotherapy Protocols</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Mélanome</term><term>Tumeurs cutanées</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticorps monoclonaux</term><term>Antinéoplasiques</term><term>Inhibiteurs de protéines kinases</term><term>Médicaments en essais cliniques</term><term>Protocoles de polychimiothérapie antinéoplasique</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Clinical Trials as Topic</term><term>Humans</term><term>Kaplan-Meier Estimate</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Essais cliniques comme sujet</term><term>Estimation de Kaplan-Meier</term><term>Humains</term><term>Immunothérapie</term><term>Thérapie moléculaire ciblée</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The treatment of metastatic melanoma is still undergoing a process of major change. The two most important novel therapeutic strategies, selective kinase inhibitors and immune checkpoint blockers, both significantly prolong survival times of patients with advanced metastatic disease. Different agents, dose regimens and combinations have been tested against each other vigorously within these two groups. However, results from prospective head-to-head comparative studies of both strategies are still lacking. We performed an exploratory analysis of survival data from selected clinical trials representative for the new treatment strategies in advanced metastatic melanoma. Eighty-three Kaplan-Meier survival curves from 25 trials were digitised and grouped by therapeutic strategy and treatment line. For each of these groups, mean survival curves were generated for progression-free (PFS) and overall survival (OS) by weighted averaging. Survival curves grouped together by therapeutic strategy revealed a high concordance, particularly in the first-line setting. For kinase inhibitors, the most favourable PFS and OS in all therapy lines were observed for combined BRAF plus MEK inhibition. For immune checkpoint inhibitors, combined PD-1 plus CTLA-4 inhibition demonstrated the best survival outcome in all categories except for OS in first-line therapy. For the latter, combined PD-1 plus CTLA-4 inhibition showed similar outcomes as single-agent PD-1 inhibition. Comparison of kinase inhibitors and checkpoint blockers revealed a superiority of combined BRAF plus MEK inhibition within the first 6 months, later changing to a superiority of PD-1 blockers alone or in combination with CTLA-4 blockers. These results need confirmation by prospective clinical trials.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Italie</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Bade-Wurtemberg</li><li>Californie</li><li>District de Tübingen</li><li>Grand Londres</li><li>Grand Manchester</li><li>Massachusetts</li><li>Nouvelle-Galles du Sud</li><li>Provence-Alpes-Côte d'Azur</li><li>Schleswig-Holstein</li><li>Victoria (État)</li></region><settlement><li>Kiel</li><li>Londres</li><li>Manchester</li><li>Marseille</li><li>Melbourne</li><li>Sydney</li><li>Tübingen</li></settlement><orgName><li>Université de Manchester</li><li>Université de Melbourne</li><li>Université de Sydney</li></orgName></list><tree><country name="Allemagne"><noRegion><name sortKey="Ugurel, Selma" sort="Ugurel, Selma" uniqKey="Ugurel S" first="Selma" last="Ugurel">Selma Ugurel</name></noRegion><name sortKey="Garbe, Claus" sort="Garbe, Claus" uniqKey="Garbe C" first="Claus" last="Garbe">Claus Garbe</name><name sortKey="Hauschild, Axel" sort="Hauschild, Axel" uniqKey="Hauschild A" first="Axel" last="Hauschild">Axel Hauschild</name><name sortKey="Rohmel, Joachim" sort="Rohmel, Joachim" uniqKey="Rohmel J" first="Joachim" last="Röhmel">Joachim Röhmel</name><name sortKey="Schadendorf, Dirk" sort="Schadendorf, Dirk" uniqKey="Schadendorf D" first="Dirk" last="Schadendorf">Dirk Schadendorf</name></country><country name="Italie"><noRegion><name sortKey="Ascierto, Paolo A" sort="Ascierto, Paolo A" uniqKey="Ascierto P" first="Paolo A" last="Ascierto">Paolo A. Ascierto</name></noRegion></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Flaherty, Keith T" sort="Flaherty, Keith T" uniqKey="Flaherty K" first="Keith T" last="Flaherty">Keith T. Flaherty</name></region><name sortKey="Ribas, Antoni" sort="Ribas, Antoni" uniqKey="Ribas A" first="Antoni" last="Ribas">Antoni Ribas</name></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Grob, Jean Jacques" sort="Grob, Jean Jacques" uniqKey="Grob J" first="Jean Jacques" last="Grob">Jean Jacques Grob</name></region><name sortKey="Robert, Caroline" sort="Robert, Caroline" uniqKey="Robert C" first="Caroline" last="Robert">Caroline Robert</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Larkin, James" sort="Larkin, James" uniqKey="Larkin J" first="James" last="Larkin">James Larkin</name></region><name sortKey="Lorigan, Paul" sort="Lorigan, Paul" uniqKey="Lorigan P" first="Paul" last="Lorigan">Paul Lorigan</name></country><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Long, Georgina V" sort="Long, Georgina V" uniqKey="Long G" first="Georgina V" last="Long">Georgina V. Long</name></region><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A" last="Mcarthur">Grant A. Mcarthur</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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