A systematic review of phase II trials exploring anti-PD-1/PD-L1 combinations in patients with solid tumors
A partir d'une revue systématique des essais de phase II (119 articles), cette étude analyse l'efficacité et la toxicité des anti-PD-1/PD-L1 dispensés en combinaison avec d'autres traitements anticancéreux systémiques ou localisés chez des patients atteints d'une tumeur solide
Background : A high number of combinations of PD-1/PD-L1 inhibitors with other anti-cancer therapiesare in clinical development. The usefulness of phase II trials in evaluating theirefficacy and safety is unclear. Materials and methods : We performed a systematic search on PubMed and Cochrane Library for phase II trialsof PD-1/PD-L1 inhibitors in combination with other anti-cancer therapies (systemictherapy and/or radiotherapy) published between January 1st 2018 and December 31st 2020. Study design, primary endpoint and main outcomes were registered for each paper. Results : 119 articles reporting on 65 regimens were included in our analysis. Backbone agentswere more frequently PD-1 inhibitors (pembrolizumab=47, nivolumab=41, camrelizumab=3)followed by anti-PD-L1 (durvalumab=19, atezolizumab=6, avelumab=3). Therapeutic partnerswere other immunotherapeutic agents (n=46), targeted therapies (n=40), chemotherapy(n=22) or radiotherapy (n=11). The majority of articles reported on single-arm trials(n=87, 73%) and response rate was the most frequent primary endpoint (n=69, 58%).Objective responses, registered in 109 (92%) articles, ranged between 0% to 91%. Theincidence of grade 3 or higher treatment-related adverse events, clearly reportedin 97 (82%) articles, spanned from 0 to 100%. Five combinations received regulatoryapproval by Food and Drug Administration or European Medicine Agency for 9 differentindications, based on the results of a phase II trial (n=3) or on a confirmatory phaseIII trial (n=6). Conclusions : The landscape of phase II trials evaluating PD-1/PD-L1 inhibitors with other anticancertherapies is heterogeneous. Combinations of two immunotherapeutic agents have beenthe most investigated. Only a minority of indications (8%) granted regulatory approval.