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

Risultato della ricerca: Articlepeer review

Abstract

Background: The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lungcancer (NSCLC) therapy over the last few years. However, establishing the optimal therapeutic optionsamong programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clinicalsetting.Methods: We performed a systematic review and finally included eleven first-line randomized controlledtrials to compare efficacy and safety outcomes among first-line IO treatment strategies versus standardplatinum-based chemotherapy (CT) according to PD-L1 expression level (<1%, 1–49%, ≥50%). Pooledhazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), overall survival (OS), objectiveresponse 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, ComboIO, IO+CT) the IO + CT approach resulted in a significant increase of the ORR, albeit with no relevantimprovement 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 + CTand the dual checkpoint blockade. Of note, in the PD-L1 1–49% subgroup, the use of anti-PD-1 agentsin association with CT led to a statistically significant gain in OS. As concerns safety, the dual checkpointblockade seemed to be better tolerated than IO+CT.Conclusions: This meta-analysis suggested the current limited role of PD-1/CTLA-4 inhibitorscombination in PD-L1-high and/or -low advanced NSCLC patients while emerging as a potentially effectiveand tolerable option in particular PD-L1 negative subgroups
Lingua originaleEnglish
Numero di pagine25
RivistaTranslational Lung Cancer Research
Stato di pubblicazionePublished - 2021

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