Comparative assessment of early mortality risk upon immunecheckpoint inhibitors alone or in combinations with other agents across solid malignancies: a systematic review and meta-analysis
A partir d'une revue systématique de la littérature (56 essais randomisés, 40 215 patients, 14 types de cancers), cette méta-analyse évalue le taux de décès prématurés (décès intervenu au cours des 3 premiers mois de traitement) chez des patients atteints d'une tumeur solide et traités par inhibiteurs de points de contrôle immunitaires, dispensés seuls ou en combinaison avec d'autres agents thérapeutiques
Résumé en anglais
Background : The early crossing of survival curves in randomized clinical trials (RCTs) with immune checkpoint blockers (ICB) suggests an excess of mortality in the first months of treatment. However, the exact estimation of the early death (ED) rate, the comparison between ED upon ICI alone or in combination with other agents and the impact of tumor type and PD-L1 expression on ED are unknown.
Methods : RCTs comparing ICI alone (ICI-only group) or in combination with other non-ICI therapies (ICI-OT group) (experimental arms) vs non-ICI treatments (control arm) were included. ED was defined as death within the first 3 months of treatment. The primary outcome was the comparison of ED between experimental and control arms, the secondary outcome was the comparison of ED risk between ICI-only and ICI-OT. ED rates estimated by risk-ratio (RR) were pooled by random effect model.
Results : 56 RCTs (40215 participants, 14 cancer types) were included. ED occurred in 14.2% and 6.7% of patients in ICI-only and ICI-OT groups, respectively. ED risk significantly increased with ICI-only (RR: 1.29, 95% CI 1.05-1.57) versus non-ICI therapies while it was lower with ICI-OT versus non-ICI treatments (RR: 0.81, 95% CI 0.73-0.90). ED risk was significantly higher upon ICI-only compared to ICI-OT (RR: 1.57, 95% CI 1.26-1.95). Gastric and urothelial carcinoma were at higher risk of ED. PD-L1 expression and ICI drug classes were not associated with ED.
Conclusions : ED upon first-line ICI is a clinically relevant phenomenon across solid malignancies, not predictable by PD-L1 expression, but preventable through the addition of other treatments to ICI.
