PMID- 37962220 OWN - NLM STAT- MEDLINE DCOM- 20231225 LR - 20240416 IS - 1473-5636 (Electronic) IS - 0960-8931 (Print) IS - 0960-8931 (Linking) VI - 34 IP - 1 DP - 2024 Feb 1 TI - Effectiveness, safety and utilization of cobimetinib and vemurafenib in patients with BRAF V600 mutant melanoma with and without cerebral metastasis under real-world conditions in Germany: the non-interventional study coveNIS. PG - 44-53 LID - 10.1097/CMR.0000000000000908 [doi] AB - Cobimetinib/vemurafenib combination therapy is approved for treatment of adults with unresectable or metastatic BRAF V600 mutated malignant melanoma (mM). The non-interventional post-authorisation safety study coveNIS collected real-world data on cobimetinib/vemurafenib treatment focussing on overall survival (OS), safety and utilization. MM patients with brain metastases are usually excluded from clinical studies. coveNIS observed 2 cohorts: mM patients without (Cohort A) and with cerebral metastases (Cohort B), aiming to close the data gap for the latter population. A direct comparison of the 2 cohorts was not intended. The primary effectiveness objective was OS; the safety objective was the incidence of all and of serious adverse events (AEs). Secondary objectives included progression-free survival (PFS), time to development of cerebral metastasis (Cohort A) and time to central nervous system relapse (Cohort B). All statistical analyses were descriptive. Between 2017 and 2021, 95 patients were included (Cohort A: 54, Cohort B: 41 patients) at 32 sites in Germany. Median OS was 21.6 months in Cohort A, 7.4 months in Cohort B. Median PFS was 6.9 months in Cohort A, 5.2 months in Cohort B. The proportion of patients experiencing any AEs was 83.3% (Cohort A) and 87.8% (Cohort B). The two most common AEs in Cohort A were 'diarrhoea' (37%), 'vomiting' (20.4%) and 'pyrexia' (20.4%); in Cohort B 'diarrhoea' (36.6%) and 'fatigue' (22%). In conclusion, the OS rates in Cohort A and Cohort B of coveNIS are in line with the OS data from other trials with BRAF/MEK inhibitors for mM. No new safety signals were observed. CI - Copyright (c) 2023 The Author(s). Published by Wolters Kluwer Health, Inc. FAU - Kahler, Katharina C AU - Kahler KC AD - UKSH Schleswig-Holstein, Campus Kiel, Klinik fur Dermatologie Venerologie und Allergologie, Kiel. FAU - Debus, Dirk AU - Debus D AD - Klinikum Nurnberg, Hautklinik, Universitatsklinik fur Dermatologie der Paracelsus Medizinischen Privatuniversitat, Nurnberg. FAU - Schley, Gaston AU - Schley G AD - HELIOS Klinikum Schwerin und universitarer Campus der MSH-Medical School Hamburg, Hautklinik, Schwerin. FAU - Goppner, Daniela AU - Goppner D AD - Universitatsklinikum Giessen, Klinik fur Dermatologie Venerologie und Allergologie, Giessen. FAU - Hassel, Jessica C AU - Hassel JC AD - Universitatsklinikum Heidelberg, Hautklinik und Nationales Centrum fur Tumorerkrankungen, Heidelberg. FAU - Meier, Friedegund AU - Meier F AD - Klinik und Poliklinik fur Dermatologie, Universitatsklinikum Carl Gustav Carus an der Technischen Universitat Dresden, Hauttumorzentrum am Nationalen Centrum fur Tumorerkrankungen und Universitats KrebsCentrum Dresden, Dresden. FAU - Terheyden, Patrick AU - Terheyden P AD - UKSH Schleswig-Holstein, Campus Lubeck, Klinik fur Dermatologie Allergologie und Venerologie, Lubeck. FAU - Stadler, Rudolf AU - Stadler R AD - Universitatsklinik fur Dermatologie, Johannes Wesling Klinikum, Minden, Klinikum der Ruhr-Universitat Bochum (UK-RUB). FAU - Tuting, Thomas AU - Tuting T AD - Universitatshautklinik Magdeburg, Klinik fur Dermatologie und Venerologie, Magdeburg. FAU - Kaatz, Martin AU - Kaatz M AD - SRH Wald-Klinikum gGmbH, Klinik fur Hautkrankheiten und Allergologie, Gera. FAU - Hoff, Norman-Philipp AU - Hoff NP AD - Universitatsklinikum Dusseldorf, Klinik fur Dermatologie, Dusseldorf. FAU - Masoudi, Ehsan AU - Masoudi E AD - Roche Pharma AG, Grenzach-Wyhlen. FAU - Zdanowicz-Specht, Agnieszka AU - Zdanowicz-Specht A AD - Roche Pharma AG, Grenzach-Wyhlen. FAU - Nguyen, Minh Tam AU - Nguyen MT AD - Roche Pharma AG, Grenzach-Wyhlen. FAU - Mohr, Peter AU - Mohr P AD - Elbe Klinikum Buxtehude, Klinik fur Dermatologie, Buxtehude, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231113 PL - England TA - Melanoma Res JT - Melanoma research JID - 9109623 RN - 207SMY3FQT (Vemurafenib) RN - ER29L26N1X (cobimetinib) RN - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.11.1 (BRAF protein, human) SB - IM MH - Adult MH - Humans MH - Vemurafenib/pharmacology/therapeutic use MH - *Melanoma/drug therapy/genetics MH - Proto-Oncogene Proteins B-raf/genetics/therapeutic use MH - *Skin Neoplasms/pathology MH - Mutation MH - Neoplasm Recurrence, Local/drug therapy MH - Protein Kinase Inhibitors/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects PMC - PMC10732299 COIS- K.C.K. has received honoraria or consultancy honoraria from Bristol-Myers Squibb, MSD, Novartis and Sanofi-Aventis; research funding from Novartis; and travel support from Bristol-Myers Squibb, MSD, Novartis and Roche. D.D. has received consultancy and lecture honoraria or support for travel expenses / participation fees by Amgen, BMS, Kyowa Kirin, MSD, Mylan, Novartis, Pfizer, Pierre Fabre, Roche and Sanofi. G.S. has received honoraria from Bristol-Myers Squibb, Novartis, Merck Sharp & Dohme and Roche. D.G. has received consultancy honoraria as well as reimbursement for travel expenses and participation fees by Bristol-Myers Squibb, Novartis, Pierre Fabre, Immunocore, Sanofi and Sun Pharma. J.C.H. has received consultancy and lecture honoraria or support for travel expenses / participation fees by Almirall, Amgen, BMS, GSK, Immunocore, MSD, Novartis, Pierre Fabre, Roche, Sanofi and Sun Pharma. F.M. has received travel support or/and speaker's fees or/and advisor's honoraria by Novartis, Roche, BMS, MSD, Pierre Fabre and Sanofi; and research funding from Novartis and Roche. P.T. has received honoraria from Bristol-Myers Squibb, Novartis, Merck Sharp & Dohme, Pierre Fabre, CureVac, Merck Serono, Sanofi, Roche, Kyowa Kirin and Biofrontera; and travel support from Bristol-Myers Squibb and Pierre Fabre. R.S. has received honoraria from Kyowa Kirin, 4Sc, Takeda, Innate Pharma, Stemline, miRagen Therapeutics Inc., Recordati, Galderma, Hoffmann La Roche, Novartis, Abbvie, Janssen and Leo Pharma. T.T. has received lecture honoraria and travel support from BMS, MSD and Novartis. M.K. has received honoraria from Bristol-Myers Squibb, Novartis, Pierre Fabre, MSD, Sanofi, Roche and Sun Pharma. N.-P.H. has received honoraria from Bristol-Myers Squibb, Novartis, Roche, Kyowa Kirin; and travel support from Novartis and Pfizer. E.M., A.Z.-S. and M.T.N. are employees of Roche Pharma AG. P.M. has received consultancy and lecture honoraria or support for travel expenses / participation fees by Amgen, BMS, Beiersdorf, Immunocore, Merck Serono, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi Genzyme and Sun Pharma. EDAT- 2023/11/14 12:43 MHDA- 2023/12/25 06:43 PMCR- 2023/12/20 CRDT- 2023/11/14 07:55 PHST- 2023/12/25 06:43 [medline] PHST- 2023/11/14 12:43 [pubmed] PHST- 2023/11/14 07:55 [entrez] PHST- 2023/12/20 00:00 [pmc-release] AID - 00008390-990000000-00112 [pii] AID - 10.1097/CMR.0000000000000908 [doi] PST - ppublish SO - Melanoma Res. 2024 Feb 1;34(1):44-53. doi: 10.1097/CMR.0000000000000908. Epub 2023 Nov 13.