Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab
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Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. / Weide, Benjamin; Martens, Alexander; Hassel, Jessica C; Berking, Carola; Postow, Michael A; Bisschop, Kees; Simeone, Ester; Mangana, Johanna; Schilling, Bastian; Di Giacomo, Anna Maria; Brenner, Nicole; Kähler, Katharina; Heinzerling, Lucie; Gutzmer, Ralf; Bender, Armin; Gebhardt, Christoffer; Romano, Emanuela; Meier, Friedegund; Martus, Peter; Maio, Michele; Blank, Christian; Schadendorf, Dirk; Dummer, Reinhard; Ascierto, Paolo A; Hospers, Geke; Garbe, Claus; Wolchok, Jedd D.
In: CLIN CANCER RES, Vol. 22, No. 22, 15.11.2016, p. 5487-5496.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab
AU - Weide, Benjamin
AU - Martens, Alexander
AU - Hassel, Jessica C
AU - Berking, Carola
AU - Postow, Michael A
AU - Bisschop, Kees
AU - Simeone, Ester
AU - Mangana, Johanna
AU - Schilling, Bastian
AU - Di Giacomo, Anna Maria
AU - Brenner, Nicole
AU - Kähler, Katharina
AU - Heinzerling, Lucie
AU - Gutzmer, Ralf
AU - Bender, Armin
AU - Gebhardt, Christoffer
AU - Romano, Emanuela
AU - Meier, Friedegund
AU - Martus, Peter
AU - Maio, Michele
AU - Blank, Christian
AU - Schadendorf, Dirk
AU - Dummer, Reinhard
AU - Ascierto, Paolo A
AU - Hospers, Geke
AU - Garbe, Claus
AU - Wolchok, Jedd D
N1 - ©2016 American Association for Cancer Research.
PY - 2016/11/15
Y1 - 2016/11/15
N2 - PURPOSE: Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) after pembrolizumab treatment in melanoma patients.EXPERIMENTAL DESIGN: Serum lactate dehydrogenase (LDH), routine blood count parameters, and clinical characteristics were investigated in 616 patients. Endpoints were OS and best overall response following pembrolizumab treatment. Kaplan-Meier analysis and Cox regression were applied for survival analysis.RESULTS: Relative eosinophil count (REC) ≥1.5%, relative lymphocyte count (RLC) ≥17.5%, ≤2.5-fold elevation of LDH, and the absence of metastasis other than soft-tissue/lung were associated with favorable OS in the discovery (n = 177) and the confirmation (n = 182) cohort and had independent positive impact (all P < 0.001). Their independent role was subsequently confirmed in the validation cohort (n = 257; all P < 0.01). The number of favorable factors was strongly associated with prognosis. One-year OS probabilities of 83.9% versus 14.7% and response rates of 58.3% versus 3.3% were observed in patients with four of four compared to those with none of four favorable baseline factors present, respectively.CONCLUSIONS: High REC and RLC, low LDH, and absence of metastasis other than soft-tissue/lung are independent baseline characteristics associated with favorable OS of patients with melanoma treated with pembrolizumab. Presence of four favorable factors in combination identifies a subgroup with excellent prognosis. In contrast, patients with no favorable factors present have a poor prognosis, despite pembrolizumab, and additional treatment advances are still needed. A potential predictive impact needs to be further investigated. Clin Cancer Res; 22(22); 5487-96. ©2016 AACR.
AB - PURPOSE: Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) after pembrolizumab treatment in melanoma patients.EXPERIMENTAL DESIGN: Serum lactate dehydrogenase (LDH), routine blood count parameters, and clinical characteristics were investigated in 616 patients. Endpoints were OS and best overall response following pembrolizumab treatment. Kaplan-Meier analysis and Cox regression were applied for survival analysis.RESULTS: Relative eosinophil count (REC) ≥1.5%, relative lymphocyte count (RLC) ≥17.5%, ≤2.5-fold elevation of LDH, and the absence of metastasis other than soft-tissue/lung were associated with favorable OS in the discovery (n = 177) and the confirmation (n = 182) cohort and had independent positive impact (all P < 0.001). Their independent role was subsequently confirmed in the validation cohort (n = 257; all P < 0.01). The number of favorable factors was strongly associated with prognosis. One-year OS probabilities of 83.9% versus 14.7% and response rates of 58.3% versus 3.3% were observed in patients with four of four compared to those with none of four favorable baseline factors present, respectively.CONCLUSIONS: High REC and RLC, low LDH, and absence of metastasis other than soft-tissue/lung are independent baseline characteristics associated with favorable OS of patients with melanoma treated with pembrolizumab. Presence of four favorable factors in combination identifies a subgroup with excellent prognosis. In contrast, patients with no favorable factors present have a poor prognosis, despite pembrolizumab, and additional treatment advances are still needed. A potential predictive impact needs to be further investigated. Clin Cancer Res; 22(22); 5487-96. ©2016 AACR.
KW - Aged
KW - Antibodies, Monoclonal
KW - Antibodies, Monoclonal, Humanized
KW - Biomarkers, Tumor
KW - Cohort Studies
KW - Female
KW - Humans
KW - Kaplan-Meier Estimate
KW - L-Lactate Dehydrogenase
KW - Male
KW - Melanoma
KW - Middle Aged
KW - Prognosis
KW - Skin Neoplasms
KW - Survival Analysis
KW - Treatment Outcome
KW - Journal Article
U2 - 10.1158/1078-0432.CCR-16-0127
DO - 10.1158/1078-0432.CCR-16-0127
M3 - SCORING: Journal article
C2 - 27185375
VL - 22
SP - 5487
EP - 5496
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 22
ER -
