Transcript Ipi or vem? - Imedex, LLC

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)
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 fact
After >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’
Vemurafenib, an on target therapy to
block the driver cancer signal
BRAF
MEK
ERK
Cancer growth
and survival
Vemurafenib, an on target therapy to
block the driver cancer signal
BRAF
MEK
ERK
Cancer growth
and survival
Vemurafenib, an on target therapy to
block the driver cancer signal
BRAF
MEK
ERK
ipilimumab
Cancer growth
and survival
ipi and vem in phase 2 testing as second
line therapy for metastatic melanoma
No. patients
Response rate
Ipi phase 2
Vem phase 2
155
132
5.8%
53%
Median OS
10.2 months
Toxic deaths
5 patients
Journal
publication
O’Day et al. 2010
Annals Oncology
(IF 6.45)
10 times higher
15.9 months6 months longer
0 patients
Sosman et al. 2012
NEJM 10 times higher
(IF 53.48)
OS
HR = 0.66
Time to
results
> 3 years
HR = 0.72
HR = 0.37
> 3 years
1 month
PFS
HR = 0.64
HR = 0.76
HR = 0.26
Time to response and progression according
to baseline LDH
Less aggressive
melanomas, more
frequent durable
responses
Time on study by
LDH level at baseline
Normal
1.0-1.5 x ULN
Timexon
study
>1.5
ULN
Time to response
Progressive disease
Continued
Continued response
response
More aggressive
melanomas, unlikely to
respond to ipi but had
benefit with vem
0
2
Approx timing
of CT
assessments
4
6
8
Time (months)
10
12
14
Median duration of response = 6.7 months (95% CI: 5.6, 9.8; range 1.3–12.7)
16
Let me think about this?
Eureka!!
Je le trouve
To vem or not to vem?
this is the question
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