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What should patients with BRAF mutant melanoma receive as front line therapy?. Antoni Ribas, M.D. Professor of Medicine Professor of Surgery Professor of Molecular and Medical Pharmacology Director, Tumor Immunology Program, Jonsson Comprehensive Cancer Center (JCCC) - PowerPoint PPT Presentation
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What should patients with BRAF mutant melanoma
receive as front line therapy?
Antoni Ribas, M.D.Professor of MedicineProfessor of Surgery
Professor of Molecular and Medical PharmacologyDirector, Tumor Immunology Program, Jonsson
Comprehensive Cancer Center (JCCC)University of California Los Angeles (UCLA)
Chair, Melanoma Committee at SWOG
Discuss melanoma treatments with Mike Atkins…
Let’s stick to the facts of melanoma
treatment
The hard factAfter >40 years of modern medical oncology and
>3,000 clinical trials, only 3 agents have improved overall survival (OS) in melanoma:
– ipilimumab
– vemurafenib
– trametinib
Data collected using PubMed; search criteria ‘melanoma clinical trial’
Cancer growth and survival
BRAF
MEK
ERK
Vemurafenib, an on target therapy to block the driver cancer signal
Cancer growth and survival
BRAF
MEK
ERK
Vemurafenib, an on target therapy to block the driver cancer signal
Cancer growth and survival
BRAF
MEK
ERK
Vemurafenib, an on target therapy to block the driver cancer signal
ipilimumab
ipi and vem in phase 2 testing as second line therapy for metastatic melanoma
Ipi phase 2 Vem phase 2
No. patients 155 132
Response rate 5.8% 53%
Median OS 10.2 months 15.9 months
Toxic deaths 5 patients 0 patients
Journal publication
O’Day et al. 2010
Annals Oncology
(IF 6.45)
Sosman et al. 2012
NEJM
(IF 53.48)
10 times higher10 times higher
10 times higher10 times higher
6 months longer6 months longer
OS
HR = 0.66 HR = 0.72 HR = 0.37
Time to results
> 3 years > 3 years 1 month
PFS
HR = 0.64 HR = 0.76 HR = 0.26
Time to response and progression according to baseline LDH
16140
Approx timing of CT assessments
Approx timing of CT assessments
Continued response
Progressive diseaseProgressive disease
Time to responseTime to response
Time (months)4 6 8 10 122
Time on studyTime on study
Median duration of response = 6.7 months (95% CI: 5.6, 9.8; range 1.3–12.7)
Time on study byLDH level at baseline
Continued response
Time to responseTime to response
1.0-1.5 x ULN>1.5 x ULN
Progressive diseaseProgressive disease
Normal
Less aggressive melanomas, more frequent durable responses
More aggressive melanomas, unlikely to respond to ipi but had benefit with vem
Let me think about this?
To vem or not to vem? this is the question
Eureka!! Je le trouve
Conclusions
• Only 3 agents have improved OS in metastatic melanoma after >3000 clinical trials
• In patients with BRAFV600 mutant metastatic melanoma, BRAF inhibitors should be the first line choice of therapy