دورية أكاديمية
Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600–Mutant Unresectable or Metastatic Melanoma
| العنوان: | Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600–Mutant Unresectable or Metastatic Melanoma |
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| المؤلفون: | Dummer, Reinhard, Long, Georgina V, Robert, Caroline, Tawbi, Hussein A, Flaherty, Keith T, Ascierto, Paolo A, Nathan, Paul D, Rutkowski, Piotr, Leonov, Oleg, Dutriaux, Caroline, Mandalà, Mario, Lorigan, Paul, Ferrucci, Pier Francesco, Grob, Jean Jacques, Meyer, Nicolas, Gogas, Helen, Stroyakovskiy, Daniil, Arance, Ana, Brase, Jan C, Green, Steven, Haas, Tomas, Masood, Aisha, Gasal, Eduard, Ribas, Antoni, Schadendorf, Dirk |
| المصدر: | Dummer, Reinhard; Long, Georgina V; Robert, Caroline; Tawbi, Hussein A; Flaherty, Keith T; Ascierto, Paolo A; Nathan, Paul D; Rutkowski, Piotr; Leonov, Oleg; Dutriaux, Caroline; Mandalà, Mario; Lorigan, Paul; Ferrucci, Pier Francesco; Grob, Jean Jacques; Meyer, Nicolas; Gogas, Helen; Stroyakovskiy, Daniil; Arance, Ana; Brase, Jan C; Green, Steven; Haas, Tomas; Masood, Aisha; Gasal, Eduard; Ribas, Antoni; Schadendorf, Dirk (2022). Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600–Mutant Unresectable or Metastatic Melanoma. Journal of Clinical Oncology, 40(13):1428-1438. |
| بيانات النشر: | American Society of Clinical Oncology |
| سنة النشر: | 2022 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Dermatology Clinic, 610 Medicine & health, Cancer Research, Oncology |
| الوصف: | PURPOSE Preclinical data suggest the combination of an anti–programmed death receptor 1 antibody plus dabrafenib and trametinib to have superior antitumor activity compared with dabrafenib plus trametinib alone. These observations are supported by translational evidence suggesting that immune checkpoint inhibitors plus targeted therapy may improve treatment outcomes in patients with BRAF V600–mutant metastatic melanoma. COMBI-i is a phase III trial evaluating spartalizumab, an anti–programmed death receptor 1 antibody, in combination with dabrafenib and trametinib (sparta-DabTram), versus placebo plus dabrafenib and trametinib (placebo-DabTram) in patients with BRAF V600–mutant unresectable or metastatic melanoma. METHODS Patients received spartalizumab 400 mg intravenously every 4 weeks plus dabrafenib 150 mg orally twice daily and trametinib 2 mg orally once daily or placebo-DabTram. Participants were age ≥ 18 years with unresectable or metastatic BRAF V600–mutant melanoma. The primary end point was investigator-assessed progression-free survival. Overall survival was a key secondary end point (ClinicalTrials.gov identifier: NCT02967692 ). RESULTS At data cutoff (July 1, 2020), the median progression-free survival was 16.2 months (95% CI, 12.7 to 23.9 months) in the sparta-DabTram arm versus 12.0 months (95% CI, 10.2 to 15.4 months) in the placebo-DabTram arm (hazard ratio, 0.82 [95% CI, 0.66 to 1.03]; P = .042 [one-sided; nonsignificant]). The objective response rates were 69% (183 of 267 patients) versus 64% (170 of 265 patients), respectively. Grade ≥ 3 treatment-related adverse events occurred in 55% (146 of 267) of patients in the sparta-DabTram arm and 33% (88 of 264) in the placebo-DabTram arm. CONCLUSION The study did not meet its primary end point; broad first-line use of sparta-DabTram is not supported by these results. Further biomarker-driven investigation may identify patient subpopulations who could benefit from checkpoint inhibitor plus targeted therapy combinations. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0732-183X |
| العلاقة: | https://www.zora.uzh.ch/id/eprint/213526/1/928_Dummer_R._et_al._Randomized_Phase_III_Trial_Evaluationg_Spartalizumab_plus_Dabrafenib_and_Trametinib_for_BRAF_V600_mutant_JCO_2022.pdfTest; info:pmid/35030011; urn:issn:0732-183X |
| DOI: | 10.5167/uzh-213526 |
| DOI: | 10.1200/jco.21.01601 |
| الإتاحة: | https://doi.org/10.5167/uzh-21352610.1200/jco.21.01601Test https://www.zora.uzh.ch/id/eprint/213526Test/ https://www.zora.uzh.ch/id/eprint/213526/1/928_Dummer_R._et_al._Randomized_Phase_III_Trial_Evaluationg_Spartalizumab_plus_Dabrafenib_and_Trametinib_for_BRAF_V600_mutant_JCO_2022.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess ; Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.8E0645B8 |
| قاعدة البيانات: | BASE |
| تدمد: | 0732183X |
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| DOI: | 10.5167/uzh-213526 |