Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial
Abstract No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBI...
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Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44475-6 |
| _version_ | 1827388316836691968 |
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| author | Paolo A. Ascierto Milena Casula Jenny Bulgarelli Marina Pisano Claudia Piccinini Luisa Piccin Antonio Cossu Mario Mandalà Pier Francesco Ferrucci Massimo Guidoboni Piotr Rutkowski Virginia Ferraresi Ana Arance Michele Guida Evaristo Maiello Helen Gogas Erika Richtig Maria Teresa Fierro Celeste Lebbe Hildur Helgadottir Paola Queirolo Francesco Spagnolo Marco Tucci Michele Del Vecchio Maria Gonzales Cao Alessandro Marco Minisini Sabino De Placido Miguel F. Sanmamed Domenico Mallardo Miriam Paone Maria Grazia Vitale Ignacio Melero Antonio M. Grimaldi Diana Giannarelli Reinhard Dummer Vanna Chiarion Sileni Giuseppe Palmieri |
| author_facet | Paolo A. Ascierto Milena Casula Jenny Bulgarelli Marina Pisano Claudia Piccinini Luisa Piccin Antonio Cossu Mario Mandalà Pier Francesco Ferrucci Massimo Guidoboni Piotr Rutkowski Virginia Ferraresi Ana Arance Michele Guida Evaristo Maiello Helen Gogas Erika Richtig Maria Teresa Fierro Celeste Lebbe Hildur Helgadottir Paola Queirolo Francesco Spagnolo Marco Tucci Michele Del Vecchio Maria Gonzales Cao Alessandro Marco Minisini Sabino De Placido Miguel F. Sanmamed Domenico Mallardo Miriam Paone Maria Grazia Vitale Ignacio Melero Antonio M. Grimaldi Diana Giannarelli Reinhard Dummer Vanna Chiarion Sileni Giuseppe Palmieri |
| author_sort | Paolo A. Ascierto |
| collection | DOAJ |
| description | Abstract No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy. |
| first_indexed | 2024-03-08T16:17:07Z |
| format | Article |
| id | doaj.art-2b98c18ea9d84e45baec87cc1752497f |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T16:17:07Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-2b98c18ea9d84e45baec87cc1752497f2024-01-07T12:32:28ZengNature PortfolioNature Communications2041-17232024-01-0115111210.1038/s41467-023-44475-6Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trialPaolo A. Ascierto0Milena Casula1Jenny Bulgarelli2Marina Pisano3Claudia Piccinini4Luisa Piccin5Antonio Cossu6Mario Mandalà7Pier Francesco Ferrucci8Massimo Guidoboni9Piotr Rutkowski10Virginia Ferraresi11Ana Arance12Michele Guida13Evaristo Maiello14Helen Gogas15Erika Richtig16Maria Teresa Fierro17Celeste Lebbe18Hildur Helgadottir19Paola Queirolo20Francesco Spagnolo21Marco Tucci22Michele Del Vecchio23Maria Gonzales Cao24Alessandro Marco Minisini25Sabino De Placido26Miguel F. Sanmamed27Domenico Mallardo28Miriam Paone29Maria Grazia Vitale30Ignacio Melero31Antonio M. Grimaldi32Diana Giannarelli33Reinhard Dummer34Vanna Chiarion Sileni35Giuseppe Palmieri36Department of Melanoma, Cancer Immunotherapy and Development Therapeutics. I.N.T. IRCCS Fondazione “G. Pascale”Immuno-Oncology & Targeted Cancer Biotherapies, University of Sassari - Unit of Cancer Genetics, IRGB-CNRImmunotherapy, Cell Therapy Unit and Biobank Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”Immuno-Oncology & Targeted Cancer Biotherapies, University of Sassari - Unit of Cancer Genetics, IRGB-CNRImmunotherapy, Cell Therapy Unit and Biobank Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”Melanoma Oncology Unit, Veneto Institute of Oncology IOV-IRCCSDepartment of Medicine, Surgery and Pharmacy, University of SassariUniversity of PerugiaBiotherapy of Tumors Unit, Department of Experimental Oncology, European Institute of Oncology, IRCCSImmunotherapy, Cell Therapy Unit and Biobank Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska Curie National Research Institute of Oncology, 02-781 –Department of Medical Oncology 1, IRCCS Regina Elena National Cancer InstituteDepartment of Medical Oncology, Hospital Clínic BarcelonaRare Tumors and Melanoma Unit, IRCCS Istituto dei Tumori “Giovanni Paolo II”Oncology Unit, Foundation IRCCS Casa Sollievo della SofferenzaFirst Department of Medicine, National and Kapodistrian University of AthensDepartment of Dermatology, Medical University of GrazDepartment of Medical Sciences, Dermatologic Clinic, University of TurinDermato-Oncology and CIC AP-HP Hôpital Saint Louis,Cancer Institute APHP. Nord-Université Paris Cite F-75010Department of Oncology-Pathology, Karolinska Institutet and Karolinska University Hospital SolnaSkin Cancer Unit, IRCCS Ospedale Policlinico San MartinoSkin Cancer Unit, IRCCS Ospedale Policlinico San MartinoDepartment of Interdisciplinary Medicine, Oncology Unit, University of Bari “Aldo Moro”Unit of Melanoma Medical Oncology, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei TumoriDepartment of Medical Oncology, University Hospital DexeusAcademic Hospital “Santa Maria della Misericordia”Department of Clinical Medicine and Surgery, University of Naples “Federico II”Department of Interdisciplinary Medicine, Oncology Unit, University of Bari “Aldo Moro”Department of Melanoma, Cancer Immunotherapy and Development Therapeutics. I.N.T. IRCCS Fondazione “G. Pascale”Department of Melanoma, Cancer Immunotherapy and Development Therapeutics. I.N.T. IRCCS Fondazione “G. Pascale”Department of Melanoma, Cancer Immunotherapy and Development Therapeutics. I.N.T. IRCCS Fondazione “G. Pascale”Department of Immunology and Oncology, Clínica Universidad de NavarraDepartment of Melanoma, Cancer Immunotherapy and Development Therapeutics. I.N.T. IRCCS Fondazione “G. Pascale”Fondazione Policlinico Universitario A. Gemelli, IRCCS – Facility of Epidemiology and BiostatisticsDepartment of Dermatology, University and University Hospital ZurichMelanoma Oncology Unit, Veneto Institute of Oncology IOV-IRCCSImmuno-Oncology & Targeted Cancer Biotherapies, University of Sassari - Unit of Cancer Genetics, IRGB-CNRAbstract No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.https://doi.org/10.1038/s41467-023-44475-6 |
| spellingShingle | Paolo A. Ascierto Milena Casula Jenny Bulgarelli Marina Pisano Claudia Piccinini Luisa Piccin Antonio Cossu Mario Mandalà Pier Francesco Ferrucci Massimo Guidoboni Piotr Rutkowski Virginia Ferraresi Ana Arance Michele Guida Evaristo Maiello Helen Gogas Erika Richtig Maria Teresa Fierro Celeste Lebbe Hildur Helgadottir Paola Queirolo Francesco Spagnolo Marco Tucci Michele Del Vecchio Maria Gonzales Cao Alessandro Marco Minisini Sabino De Placido Miguel F. Sanmamed Domenico Mallardo Miriam Paone Maria Grazia Vitale Ignacio Melero Antonio M. Grimaldi Diana Giannarelli Reinhard Dummer Vanna Chiarion Sileni Giuseppe Palmieri Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial Nature Communications |
| title | Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial |
| title_full | Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial |
| title_fullStr | Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial |
| title_full_unstemmed | Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial |
| title_short | Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial |
| title_sort | sequential immunotherapy and targeted therapy for metastatic braf v600 mutated melanoma 4 year survival and biomarkers evaluation from the phase ii secombit trial |
| url | https://doi.org/10.1038/s41467-023-44475-6 |
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