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Prognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib.

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Date
2016-04
ICR Author
Gore, Martin
Larkin, James
Author
Seifert, H
Fisher, R
Martin-Liberal, J
Edmonds, K
Hughes, P
Khabra, K
Gore, M
Larkin, J
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Type
Journal Article
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Abstract
The BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti-CTLA4-antibody, ipilimumab, is a standard first-line and second-line treatment option in Europe, with a median time to response of 2-3 months, but some patients show rapid clinical deterioration before that. The aim of this analysis was to identify prognostic markers for survival after failure of vemurafenib treatment to identify patients who have a sufficient life expectancy to respond to new immunotherapy treatments. We retrospectively analysed 101 consecutive unselected patients treated with vemurafenib for metastatic melanoma at a single institution. The association between clinical parameters and death within 3 months after cessation of vemurafenib (n=69) was assessed by binary logistic and Cox regression. Of the patients, 45% died within 3 months of progression on vemurafenib. Elevated baseline serum lactate dehydrogenase, absence of normalization of serum lactate dehydrogenase on vemurafenib therapy, performance status of at least 2 at progression and time from primary tumour to metastatic disease less than 5 years were identified as poor prognostic markers. In an exploratory tumour growth kinetics analysis (n=16), we found that following cessation of vemurafenib, approximately a third each showed a stable, decelerated or accelerated rate of tumour growth. Patients with these poor prognostic markers are unlikely to have sufficient life expectancy to complete ipilimumab treatment after failure with vemurafenib. Consideration needs to be given to the elective use of immunotherapy before patients become resistant to vemurafenib. This requires prospective randomized evaluation. Our tumour growth kinetics analysis requires confirmation; however, it may suggest that intermittent vemurafenib treatment should be investigated in clinical trials.
URI
https://repository.icr.ac.uk/handle/internal/594
DOI
https://doi.org/10.1097/cmr.0000000000000218
Collections
  • Clinical Studies
Subject
Humans
Melanoma
Skin Neoplasms
Disease Progression
Sulfonamides
Indoles
Antineoplastic Agents
Prognosis
Immunotherapy
Retrospective Studies
Adolescent
Adult
Aged
Middle Aged
Female
Male
Young Adult
Vemurafenib
Research team
Melanoma and Kidney Cancer
Language
eng
License start date
2016-04
Citation
Melanoma research, 2016, 26 (2), pp. 138 - 144

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