Evaluation of clinicopathological factors in PD-1 response : derivation and validation of a prediction scale for response to PD-1 monotherapy
Menée sur une cohorte de 315 patients atteints d'un mélanome de stade avancé traité entre 2011 et 2013 par pembrolizumab ou nivolumab, cette étude multicentrique évalue la performance d'un système de score, basé sur 5 critères cliniques (niveau élevé de lactate déshydrogénase, âge inférieur à 65 ans, sexe, ipilimumab comme antécédent thérapeutique, présence de métastases hépatiques), pour prédire la réponse à un traitement anti-PD1 dispensé en monothérapie
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.
British Journal of Cancer , résumé, 2016