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Contribution of MEK Inhibition to BRAF/MEK Inhibitor Combination Treatment of BRAF-Mutant Melanoma: Part 2 of the Randomized, Open-Label, Phase III COLUMBUS Trial
PA. Ascierto, R. Dummer, HJ. Gogas, A. Arance, M. Mandala, G. Liszkay, C. Garbe, D. Schadendorf, I. Krajsova, R. Gutzmer, V. Chiarion-Sileni, C. Dutriaux, JWB. de Groot, N. Yamazaki, C. Loquai, C. Robert, KT. Flaherty
Jazyk angličtina Země Spojené státy americké
Typ dokumentu klinické zkoušky, fáze III, časopisecké články, randomizované kontrolované studie, práce podpořená grantem
NLK
Free Medical Journals
od 2004 do Před 1 rokem
Open Access Digital Library
od 1999-01-01
PubMed
37506329
DOI
10.1200/jco.22.02322
Knihovny.cz E-zdroje
- MeSH
- inhibitory proteinkinas škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- melanom * farmakoterapie genetika MeSH
- mitogenem aktivované proteinkinasy kinas MeSH
- mutace MeSH
- nádory kůže * farmakoterapie genetika MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- protoonkogenní proteiny B-raf genetika MeSH
- vemurafenib škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
PURPOSE: In COLUMBUS part 1, patients with advanced BRAFV600-mutant melanoma were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice a day (COMBO450), vemurafenib 960 mg twice a day, or encorafenib 300 mg once daily (ENCO300). As previously reported, COMBO450 improved progression-free survival (PFS) versus vemurafenib (part 1 primary end point) and ENCO300 (part 1 key secondary end point; not statistically significant). Part 2, requested by the US Food and Drug Administration, evaluated the contribution of binimetinib by maintaining the same encorafenib dosage in the combination (encorafenib 300 mg once daily plus binimetinib 45 mg twice daily [COMBO300]) and ENCO300 arms. METHODS: In part 2, patients were randomly assigned 3:1 to COMBO300 or ENCO300. ENCO300 (parts 1 and 2) data were combined, per protocol, for PFS analysis (key secondary end point) by a blinded independent review committee (BIRC). Other analyses included overall response rate (ORR), overall survival, and safety. RESULTS: Two hundred fifty-eight patients received COMBO300, and 86 received ENCO300. Per protocol, ENCO300 arms (parts 1 and 2 combined) were also evaluated (n = 280). The median follow-up for ENCO300 was 40.8 months (part 1) and 57.1 months (part 2). The median PFS (95% CI) was 12.9 months (10.9 to 14.9) for COMBO300 versus 9.2 months (7.4 to 11.1) for ENCO300 (parts 1 and 2) and 7.4 months (5.6 to 9.2) for ENCO300 (part 2). The hazard ratio (95% CI) for COMBO300 was 0.74 (0.60 to 0.92; two-sided P = .003) versus ENCO300 (parts 1 and 2). The ORR by BIRC (95% CI) was 68% (62 to 74) and 51% (45 to 57) for COMBO300 and ENCO300 (parts 1 and 2), respectively. COMBO300 had greater relative dose intensity and fewer grade 3/4 adverse events than ENCO300. CONCLUSION: COMBO300 improved PFS, ORR, and tolerability compared with ENCO300, confirming the contribution of binimetinib to efficacy and safety.
Cancer Center Massachusetts General Hospital Boston MA
Department of Dermatologic Oncology National Cancer Center Hospital Tokyo Japan
Department of Dermatology Klinikum Bremen Ost Gesundheitnord gGmbH Bremen Germany
Department of Dermatology National Institute of Oncology Budapest Hungary
Department of Dermatology University Hospital Essen Essen Germany
Department of Dermatology University Hospital Tübingen Tübingen Germany
Department of Dermatology University Hospital Zürich Skin Cancer Center Zürich Switzerland
Department of Medical Oncology Hospital Clinic of Barcelona Barcelona Spain
Department of Medicine Service of Dermatology Paris Saclay University Cedex France
Department of Oncologic Dermatology Bordeaux University Hospital Center Bordeaux Cédex France
German Cancer Consortium Partner Site Essen Essen Germany
Isala Oncology Center Isala Zwolle the Netherlands
Melanoma Cancer Unit Istituto Oncologico Veneto IRCCS Padua Italy
Santa Maria Misericordia Hospital University of Perugia Perugia Italy
Citace poskytuje Crossref.org
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