BACKGROUND: Adjuvant treatment has always been a cornerstone in the therapeutic approach of many cancers, considering its role in reducing the risk of relapse and, in some cases, increasing overall survival. Adjuvant immune checkpoint inhibitors have been tested in different malignancies. METHODS: We performed a meta-analysis aimed to explore the impact of adjuvant PD-1 and PD-L1 inhibitors on relapse-free survival (RFS) in cancer patients enrolled in randomized controlled clinical trials. We retrieved all phase III trials published from 15 June 2008 to 15 May 2022, evaluating PD-1/PD-L1 inhibitors monotherapy as an adjuvant treatment by searching on EMBASE, Cochrane Library, and PubMed/ Medline, and international oncological meetings' abstracts. The outcome of interest was RFS. We also performed subgroup analyses focused on age and gender. RESULTS: Overall, 8 studies, involving more than 6000 patients, were included in the analysis. The pooled results highlighted that the use of adjuvant PD-1/PD-L1 inhibitors may reduce the risk of relapse compared to control treatments (hazard ratio, 0.72; 95% confidence intervals, 0.67-0.78). In addition, the subgroup analyses observed that this benefit was consistent in different patient populations, including male, female, younger, and older patients. CONCLUSIONS: Adjuvant anti-PD-1/PD-L1 treatment is associated with an increased RFS in the overall population and in subgroups divided according to age and gender.

Department of Experimental Diagnostic and Specialty Medicine S Orsola Malpighi University Hospital University of Bologna 40138 Bologna Italy

Department of Medical Oncology Hospital Ramón y Cajal 28034 Madrid Spain

Department of Medical Oncology MD Anderson Cancer Center Madrid 28033 Madrid Spain

Department of Oncology 1st Faculty of Medicine Charles University and Thomayer University Hospital 14059 Prague Czech Republic

Hospital Santa Lucia Brasilia 70390 700 Brazil

Hospital Universitário de Brasilia Brasilia 70840 901 Brazil

Latin American Cooperative Oncology Group LACOG Porto Alegre 90619 900 Brazil

Markey Cancer Center University of Kentucky Lexington KY 40536 0293 USA

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna 40138 Bologna Italy

Oncology Unit Macerata Hospital via Santa Lucia 2 62100 Macerata Italy

Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico Don Tonino Bello Istituto di Ricerca e Cura a Carattere Scientifico Istituto Tumori Giovanni Paolo 2 Bari Viale Orazio Flacco 65 70124 Bari Italy

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