A multicenter DeCOG study on predictors of vemurafenib therapy outcome in melanoma: pretreatment impacts survival

Ugurel, S., Loquai, C., Kaehler, K., Hassel, J., Berking, C., Zimmer, L., Haubitz, I., Satzger, I., Mueller-Brenne, T., Mikhaimer, N. C., Becker, J. C., Kilian, K. J., Schadendorf, D., Heinzerling, L., Kaatz, M., Utikal, J., Goeppner, D., Pfoehler, C., Pflugfelder, A., Moessner, R. and Gutzmer, R. (2015) A multicenter DeCOG study on predictors of vemurafenib therapy outcome in melanoma: pretreatment impacts survival. Annals of Oncology, 26 3: 573-582. doi:10.1093/annonc/mdu573

Author Ugurel, S.
Loquai, C.
Kaehler, K.
Hassel, J.
Berking, C.
Zimmer, L.
Haubitz, I.
Satzger, I.
Mueller-Brenne, T.
Mikhaimer, N. C.
Becker, J. C.
Kilian, K. J.
Schadendorf, D.
Heinzerling, L.
Kaatz, M.
Utikal, J.
Goeppner, D.
Pfoehler, C.
Pflugfelder, A.
Moessner, R.
Gutzmer, R.
Title A multicenter DeCOG study on predictors of vemurafenib therapy outcome in melanoma: pretreatment impacts survival
Journal name Annals of Oncology   Check publisher's open access policy
ISSN 1569-8041
Publication date 2015-03-01
Year available 2014
Sub-type Article (original research)
DOI 10.1093/annonc/mdu573
Open Access Status Not yet assessed
Volume 26
Issue 3
Start page 573
End page 582
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Background: Kinase inhibitors targeting the BRAF V600 mutation have become standard in the treatment of metastatic melanoma. Albeit in wide clinical use, the patterns associated with therapy outcome are not fully elucidated. The present study was aimed to identify predictive factors of therapy response and survival under the BRAF inhibitor vemurafenib.

Patients and methods: This multicenter retrospective study analyzed patient, tumor, and pretreatment characteristics collected in BRAF V600-mutated stage IV melanoma patients before single-agent therapy with the BRAF inhibitor vemurafenib.

Results: A total of 300 patients from 14 centers were included into this study with a median follow-up time of 13.0 months. Median progression-free survival (PFS) was 5.1 months; median overall survival (OS) was 7.6 months. Best response under vemurafenib was associated with serum lactate dehydrogenase (LDH; ≤ versus > upper normal limit; P = 0.0000001), Eastern Cooperative Oncology Group (ECOG) overall performance status (OPS) (0 versus ≥1; P = 0.00089), and BRAF mutation subtype (V600E versus V600K; P = 0.016). Multivariate analysis identified ECOG OPS ≥1 [hazard ratio (HR)=1.88; P = 0.00005], immunotherapy pretreatment (HR = 0.53; P = 0.0067), elevated serum LDH (HR = 1.45; P = 0.012), age > 55 years (HR = 0.72; P = 0.019), and chemotherapy pretreatment (HR = 1.39; P = 0.036) as independent predictors of PFS. For OS, elevated serum LDH (HR = 1.99; P = 0.00012), ECOG OPS ≥1 (HR=1.90; P = 0.00063), age > 55 years (HR = 0.65; P = 0.011), kinase inhibitor pretreatment (HR = 1.86; P = 0.014), immunotherapy pretreatment (HR = 0.57; P = 0.025), chemotherapy pretreatment (HR = 2.17; P = 0.039), and male gender (HR = 0.70; 95%confidence interval 0.50-0.98; P = 0.039) were found as predictors.

Conclusion: Our data demonstrate that the type of pretreatment strongly influences the outcome of vemurafenib therapy, with a precedent immunotherapy showing a positive, and a prior chemotherapy and kinase inhibitors showing a negative impact on survival, respectively. Moreover, we show that the patient's OPS, serum LDH, age, and gender independently impact vemurafenib therapy outcome. These findings should be taken into account for the future design of therapy sequencing in BRAF V600 mutation- positivemelanoma patients.
Keyword BRAF inhibition
Predictive factors
Therapy outcome
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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