A model combining clinical and genomic factors to predict response to PD-1/PD-L1 blockade in advanced urothelial carcinoma
Menée à partir du séquençage de l'ADN tumoral de 62 patients atteints d'un carcinome urothélial métastatique traité par inhibiteur de point de contrôle immunitaire et menée en parallèle sur 39 patients complémentaires recevant une chimiothérapie à base de taxanes, cette étude met en évidence l'intérêt d'un modèle, combinant 2 facteurs cliniques (rapport neutrophiles/lymphocytes supérieur ou égal à 5, présence de métastases viscérales) et 1 facteur génomique (nombre de variants à simple nucléotide inférieur à 10), pour prédire la réponse à un traitement anti PD-1/PD-L1
Background : In metastatic urothelial carcinoma (mUC), predictive biomarkers that correlate with response to immune checkpoint inhibitors (ICIs) are lacking. Here, we interrogated genomic and clinical features associated with response to ICIs in mUC.
Methods : Sixty two mUC patients treated with ICI who had targeted tumour sequencing were studied. We examined associations between candidate biomarkers and clinical benefit (CB, any objective reduction in tumour size) versus no clinical benefit (NCB, no change or objective increase in tumour size). Both univariable and multivariable analyses for associations were conducted. A comparator cohort of 39 mUC patients treated with taxanes was analysed by using the same methodology.
Results : Nine clinical and seven genomic factors correlated with clinical outcomes in univariable analysis in the ICI cohort. Among the 16 factors, neutrophil-to-lymphocyte ratio (NLR) ≥5 (OR = 0.12, 95% CI, 0.01–1.15), visceral metastasis (OR = 0.05, 95% CI, 0.01–0.43) and single-nucleotide variant (SNV) count < 10 (OR = 0.04, 95% CI, 0.006–0.27) were identified as independent predictors of NCB to ICI in multivariable analysis (c-statistic = 0.90). None of the 16 variables were associated with clinical benefit in the taxane cohort.
Conclusions : This three-factor model includes genomic (SNV count >9) and clinical (NLR <5, lack of visceral metastasis) variables predictive for benefit to ICI but not taxane therapy for mUC. External validation of these hypothesis-generating results is warranted to enable use in routine clinical care.
British Journal of Cancer , résumé, 2019