Open AccessProgression patterns under BRAF inhibitor treatment and treatment beyond progression in patients with metastatic melanoma
Author(s) -
Hassel Jessica C.,
BuderBakhaya Kristina,
Bender Carolin,
Zimmer Lisa,
Weide Benjamin,
Loquai Carmen,
Ugurel Selma,
Slynko Alla,
Gutzmer Ralf
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1267
Subject(s) - medicine , tumor progression , melanoma , oncology , metastatic melanoma , progression free survival , overall survival , cancer research , cancer
Abstract Despite markedly improved treatment options for metastatic melanoma, resistance to targeted therapies such as BRAF inhibitors ( BRAF i) or BRAF i plus MEK inhibitors ( MEK i) remains a major problem. Our aim was to characterize progression on BRAF i therapy and outcome of subsequent treatment. One hundred and eighty patients with BRAF ‐mutant metastatic melanoma who had progressed on treatment with single‐agent BRAF i from February 2010 to April 2015 were included in a retrospective data analysis focused on patterns of progression, treatment beyond progression ( TBP ) and subsequent treatments after BRAF i therapy. Analysis revealed that 51.1% of patients progressed with both new and existing metastases opposed to progression of only preexisting (28.3%) or only new (20.6%) metastases. Exclusive extracranial progression occurred in 50.6% of patients compared to both extra‐ and intracranial (29.4%) or sole cerebral progression (20%). Multivariable analyses demonstrated that single site progression and primary response to BRAF i were associated with improved progression‐free survival. Progression with exclusively new or only existing metastases and a baseline Eastern Cooperative Oncology Group ( ECOG ) of 0 were associated with prolonged overall survival (OS). TBP had no significant impact on OS. Other subsequent treatments showed low efficacy with the exception of anti‐ PD ‐1 antibodies. In conclusion we identified specific patterns of progression which significantly correlate with further prognosis after progression on BRAF i treatment. In contrast to previously published data, we could not demonstrate a significant survival benefit for BRAF i TBP . Subsequent therapies had strikingly low efficacy except for PD ‐1 inhibitors.