Cargando…

Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—a trial-level meta-analysis in PD-L1 selected subgroups

BACKGROUND: The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lung cancer (NSCLC) therapy over the last few years. However, establishing the optimal therapeutic options among programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clini...

Descripción completa

Detalles Bibliográficos
Autores principales: Passiglia, Francesco, Galvano, Antonio, Gristina, Valerio, Barraco, Nadia, Castiglia, Marta, Perez, Alessandro, La Mantia, Maria, Russo, Antonio, Bazan, Viviana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350096/
https://www.ncbi.nlm.nih.gov/pubmed/34430351
http://dx.doi.org/10.21037/tlcr-21-52
Descripción
Sumario:BACKGROUND: The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lung cancer (NSCLC) therapy over the last few years. However, establishing the optimal therapeutic options among programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clinical setting. METHODS: We performed a systematic review and finally included eleven first-line randomized controlled trials to compare efficacy and safety outcomes among first-line IO treatment strategies versus standard platinum-based chemotherapy (CT) according to PD-L1 expression level (<1%, 1–49%, ≥50%). Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR), treatment-related adverse events (TRAEs), and discontinuation rates were obtained. RESULTS: Our results demonstrated that among the different IO-based strategies (single-agent IO, Combo-IO, IO + CT) the IO + CT approach resulted in a significant increase of the ORR, albeit with no relevant improvement of survival in patients with PD-L1 ≥50%. As regards patients with negative PD-L1 expression, no significant differences in terms of activity and efficacy profile have been detected between the IO + CT and the dual checkpoint blockade. Of note, in the PD-L1 1–49% subgroup, the use of anti-PD-1 agents in association with CT led to a statistically significant gain in OS. As concerns safety, the dual checkpoint blockade seemed to be better tolerated than IO + CT. CONCLUSIONS: This meta-analysis suggested the current limited role of PD-1/CTLA-4 inhibitors combination in PD-L1-high and/or -low advanced NSCLC patients while emerging as a potentially effective and tolerable option in particular PD-L1 negative subgroups.