![]() ![]() More recently, upfront combination studies, evaluating the addition of IO to platinum-based CT-regimens, have proven to synergistically enhance individual immune response, eventually leading to improved clinical outcomes, thus obtaining regulatory approval regardless of PD-L1 expression levels ( 3, 4). The anti-PD-1 agent pembrolizumab demonstrated to significantly improve progression-free survival (PFS) as well as overall survival (OS) and quality of life as compared to platinum-CT in the first-line treatment of non-oncogene addicted NSCLC with tumor PD-L1 expression higher than 50%, representing the current upfront standard for about 30% of patients with newly diagnosed metastatic disease ( 2). The introduction of IO monotherapy has initially revolutionized the second-line treatment of advanced non-small cell lung cancer (NSCLC), leading to a significant increase of 5-year survival, reaching 16% nowadays, compared to 5.5% in the chemotherapy (CT) era ( 1). The advent of immune-oncology (IO), particularly the immune-checkpoint inhibitors (ICIs) targeting the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis, represented a breakthrough in lung cancer therapy over the last few years. Keywords: Non-small cell lung cancer (NSCLC) programmed death-1/cytotoxic T-lymphocyte antigen 4 inhibitors (PD-1/CTLA-4 inhibitors) immunotherapy combined modality therapy meta-analysis As concerns safety, the dual checkpoint blockade seemed to be better tolerated than IO + CT.Ĭonclusions: 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. 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 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. 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%. 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. 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%). However, establishing the optimal therapeutic options among programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clinical setting. ![]() *These authors are equal co-last authors.īackground: The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lung cancer (NSCLC) therapy over the last few years. #These authors contributed equally to this work. Francesco Passiglia 1#, Antonio Galvano 2#, Valerio Gristina 2#, Nadia Barraco 2, Marta Castiglia 2, Alessandro Perez 2, Maria La Mantia 2, Antonio Russo 2*, Viviana Bazan 3*ġ Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Regione Gonzole 10, 10043, Orbassano, Turin, Italy 2 Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy 3 Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, ItalyĬontributions: (I) Conception and design: F Passiglia, A Galvano, V Gristina (II) Administrative support: V Bazan, A Russo (III) Provision of study materials or patients: N Barraco, A Perez, M Castiglia, M La Mantia (IV) Collection and assembly of data: F Passiglia, A Galvano, V Gristina (V) Data analysis and interpretation: F Passiglia, A Galvano, V Gristina, A Russo (VI) Manuscript writing: All authors (VII) Final approval of manuscript: All authors. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |