Evaluation of clinicopathological factors in PD-1 response: derivation and validation of a prediction scale for response to PD-1 monotherapy.
- Nosrati A Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.
- Tsai KK Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.
- Goldinger SM Department of Dermatology, University Hospital of Zurich (USZ), University of Zurich, Gloriastrasse 31, Zürich 8091, Switzerland.
- Tumeh P Division of Dermatology, Department of Medicine, University of California Los Angeles (UCLA), 200 Medical Plaza Driveway, Los Angeles, CA 90024, USA.
- Grimes B Department of Epidemiology & Biostatistics, University of California, San Francisco, 550 16th Street, San Francisco, CA 94158, USA.
- Loo K Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.
- Algazi AP Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.
- Nguyen-Kim TDL Department of Interventional Radiology, University of Zurich, Rämistrasse 100, Zürich, 8091, Switzerland.
- Levesque M Department of Dermatology, University Hospital of Zurich (USZ), University of Zurich, Gloriastrasse 31, Zürich 8091, Switzerland.
- Dummer R Department of Dermatology, University Hospital of Zurich (USZ), University of Zurich, Gloriastrasse 31, Zürich 8091, Switzerland.
- Hamid O The Angeles Clinic and Research Institute (TACRI), 11818 Wilshire Boulevard #200, Los Angeles, CA 90025, USA.
- Daud A Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA 94143, USA.
- 2017-03-22
Published in:
- British journal of cancer. - 2017
Age Factors
Aged
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Female
Gene Expression Regulation, Neoplastic
Humans
Immunotherapy
Ipilimumab
L-Lactate Dehydrogenase
Male
Melanoma
Middle Aged
Neoplasm Staging
Nivolumab
Prognosis
Programmed Cell Death 1 Receptor
English
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-1 Q2W or Q3W) or nivolumab (3 mg kg-1 Q2W) 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.
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-1 Q2W or Q3W) or nivolumab (3 mg kg-1 Q2W) 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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1038/bjc.2017.70
- PMID 28324889
- Persistent URL
- https://sonar.ch/global/documents/47513
Statistics
Document views: 25
File downloads:
- Full-text: 0