Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy.
BACKGROUND
Anti-PD-1 therapy has shown significant clinical activity in advanced melanoma. We developed and validated a clinical prediction scale for response to anti- PD-1 monotherapy.


METHODS
A total of 315 patients with advanced melanoma treated with pembrolizumab (2 or 10 mg kg-1Q2W or Q3W) or nivolumab (3 mg kg-1Q2W) at four cancer centres between 2011 to 2013 served as the setting for the present cohort study. Variables with significant association to response on a univariate analysis were entered into a forward stepwise logistic regression model and were given a score based on ORs to calculate a clinical prediction scale.


RESULTS
The developed clinical prediction scale included elevated LDH (1 point), age <65 years (1 point), female sex (1 point), history of ipilimumab treatment (2 points) and the presence of liver metastasis (2 points). The scale had an area under the receiver-operating curve (AUC) of 0.73 (95% CI 0.67, 0.80) in predicting response to therapy. The predictive performance of the score was maintained in the validation cohort (AUC 0.70 (95% CI 0.58, 0.81)) and the goodness-to-fit model demonstrated good calibration.


CONCLUSIONS
Based on a large cohort of patients, we developed and validated a simple five-factor prediction scale for the clinical activity of PD-1 antibodies in advanced melanoma patients. This scale can be used to stratify patients participating in clinical trials.
Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.
Adi
A
Nosrati
Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.
Katy K
KK
Tsai
Department of Dermatology, University Hospital of Zurich (USZ), University of Zurich, Gloriastrasse 31, Zürich 8091, Switzerland.
Simone M
SM
Goldinger
Division of Dermatology, Department of Medicine, University of California Los Angeles (UCLA), 200 Medical Plaza Driveway, Los Angeles, CA 90024, USA.
Paul
P
Tumeh
Department of Epidemiology & Biostatistics, University of California, San Francisco, 550 16th Street, San Francisco, CA 94158, USA.
Barbara
B
Grimes
Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.
Kimberly
K
Loo
Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.
Alain P
AP
Algazi
Department of Interventional Radiology, University of Zurich, Rämistrasse 100, Zürich, 8091, Switzerland.
Thi Dan Linh
TDL
Nguyen-Kim
Department of Dermatology, University Hospital of Zurich (USZ), University of Zurich, Gloriastrasse 31, Zürich 8091, Switzerland.
Mitchell
M
Levesque
Department of Dermatology, University Hospital of Zurich (USZ), University of Zurich, Gloriastrasse 31, Zürich 8091, Switzerland.
Reinhard
R
Dummer
The Angeles Clinic and Research Institute (TACRI), 11818 Wilshire Boulevard #200, Los Angeles, CA 90025, USA.
Omid
O
Hamid
Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.
Adil
A
Daud
D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D000077594:Nivolumab; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000074324:Ipilimumab; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab; D007770:L-Lactate Dehydrogenase