PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma
| العنوان: | PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma |
|---|---|
| المؤلفون: | Shannon Marshall, Alain Algazi, Sunandana Chandra, Caroline Robert, Nancy Mueller, Leonel Hernandez-Aya, Wilson H. Miller, Jose Lutzky, Marcus O. Butler, Michael D. Gordon, Paolo A. Ascierto, Antoni Ribas, Bruno Delafont, Katie M. Campbell, Donald P. Lawrence |
| المصدر: | Nature communications, vol 11, iss 1 Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020) |
| بيانات النشر: | eScholarship, University of California, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Male, Durvalumab, Skin Neoplasms, General Physics and Astronomy, B7-H1 Antigen, Cohort Studies, 0302 clinical medicine, Oximes, Antineoplastic Combined Chemotherapy Protocols, Monoclonal, 80 and over, Melanoma, Cancer, Trametinib, Aged, 80 and over, Multidisciplinary, MEK inhibitor, Imidazoles, Antibodies, Monoclonal, Middle Aged, Progression-Free Survival, Tolerability, 030220 oncology & carcinogenesis, 6.1 Pharmaceuticals, Cohort, Female, Mitogen-Activated Protein Kinases, medicine.drug, Cohort study, Diarrhea, Proto-Oncogene Proteins B-raf, Adult, medicine.medical_specialty, Pyridones, Science, Immunology, Clinical Trials and Supportive Activities, Pyrimidinones, Article, General Biochemistry, Genetics and Molecular Biology, Antibodies, 03 medical and health sciences, Young Adult, Clinical Research, Internal medicine, medicine, Humans, Author Correction, neoplasms, Aged, business.industry, Evaluation of treatments and therapeutic interventions, Dabrafenib, General Chemistry, Exanthema, medicine.disease, 030104 developmental biology, Mutation, business |
| الوصف: | Combining PD-L1 blockade with inhibition of oncogenic mitogen-activated protein kinase (MAPK) signaling may result in long-lasting responses in patients with advanced melanoma. This phase 1, open-label, dose-escalation and -expansion study (NCT02027961) investigated safety, tolerability and preliminary efficacy of durvalumab (anti–PD-L1) combined with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for patients with BRAF-mutated melanoma (cohort A, n = 26), or durvalumab and trametinib given concomitantly (cohort B, n = 20) or sequentially (cohort C, n = 22) for patients with BRAF-wild type melanoma. Adverse events and treatment discontinuation rates were more common than previously reported for these agents given as monotherapy. Objective responses were observed in 69.2% (cohort A), 20.0% (cohort B) and 31.8% (cohort C) of patients, with evidence of improved tumor immune infiltration and durable responses in a subset of patients with available biopsy samples. In conclusion, combined MAPK inhibition and anti–PD-L1 therapy may provide treatment options for patients with advanced melanoma. Immune checkpoints inhibitors or MAPK inhibitors are currently used as standard of care therapies for patients with advanced melanoma. Here the authors report a phase 1 clinical trial testing the anti-PD-L1 antibody durvalumab in combination with the BRAF inhibitor dafrafenib and the MEK inhibitor trametinib in patients with BRAFV600-mutant melanoma. |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::214f5a164c72be16363987dcb81eb292Test https://escholarship.org/uc/item/344192vkTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....214f5a164c72be16363987dcb81eb292 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |