In European journal of cancer (Oxford, England : 1990)
AIM : Anti-PD-(L)1 immunotherapies improve survival in multiple cancers but remain ineffective for most patients. We applied machine-learning algorithms and multivariate analyses on baseline medical data to estimate their relative impact on overall survival (OS) upon anti-PD-(L)1 monotherapies.
METHOD : This prognostic/predictive study retrospectively analysed 33 baseline routine medical variables derived from computed tomography (CT) images, clinical and biological meta-data. 695 patients with a diagnosis of advanced cancer were treated in prospective clinical trials in a single tertiary cancer centre in 3 cohorts including systemic anti-PD-(L)1 (251, 235 patients) versus other systemic therapies (209 patients). A random forest model combined variables to identify the combination (signature) which best estimated OS in patients treated with immunotherapy. The performance for estimating OS [95%CI] was measured using Kaplan-Meier Analysis and Log-Rank test.
RESULTS : Elevated serum lactate dehydrogenase (LDHhi) and presence of liver metastases (LM+) were dominant and independent predictors of short OS in independent cohorts of melanoma and non-melanoma solid tumours. Overall, LDHhiLM+ patients treated with anti-PD-(L)1 monotherapy had a poorer outcome (median OS: 3.1[2.4-7.8] months]) compared to LDHlowLM-patients (median OS: 15.3[8.9-NA] months; P < 0.0001). The OS of LDHlowLM-patients treated with immunotherapy was 28.8[17.9-NA] months (vs 13.1[10.8-18.5], P = 0.02) in the overall population and 30.3[19.93-NA] months (vs 14.1[8.69-NA], P = 0.0013) in patients with melanoma.
CONCLUSION : LDHhiLM+ status identifies patients who shall not benefit from anti-PD-(L)1 monotherapy. It could be used in clinical trials to stratify patients and eventually address this specific medical need.
Dercle Laurent, Ammari Samy, Roblin Elvire, Bigorgne Amelie, Champiat Stéphane, Taihi Lokmane, Plaian Athèna, Hans Sophie, Lakiss Sara, Tselikas Lambros, Rouanne Mathieu, Deutsch Eric, Schwartz Lawrence H, Gönen Mithat, Flynn Jessica, Massard Christophe, Soria Jean-Charles, Robert Caroline, Marabelle Aurélien
2022-Sep-30
Cancer immunotherapy, Hyperprogression, Lactate dehydrogenase, Liver metastases, Machine learning, Survival
