PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis

Abstract

This network meta-analysis (NMA) evaluates the safety of first-line programmed death-ligand 1 (PD-L1) inhibitor monotherapy in advanced NSCLC patients compared to platinum-based chemotherapy. We also compared the risk of adverse events (AEs) according to programmed cell death-1 receptor (PD-1) or PD-L1 inhibitors therapy. To that end, we conducted a series of metanalyses (MAs) using data from six phase III clinical trials, including 4053 patients. Our results show a reduced risk of any grade treatment-related AEs (risk ratio (RR) = 0.722 95% CI: 0.667–0.783, p = 0.002), and grade 3–5 AEs (RR = 0.406 95% CI: 0.340–0.485, p = 0.023) in immunotherapy as compared to chemotherapy. In contrast, a higher risk of immune-related AEs (irAEs) was estimated for immunotherapy versus chemotherapy. The subgroup MAs comparing PD-L1 to PD-1 inhibitors, determined a lower risk of AEs leading to treatment discontinuation in the anti-PD-L1 subgroup (RR = 0.47 95% CI: 0.29–0.75, p = 0.001); however, this statistically significant difference between anti-PD-L1 and anti-PD-1 subgroups was not reached for other safety outcomes analyzed. In conclusion, our findings show that PD-L1 inhibitor monotherapy improves safety outcomes in the 1L treatment of advanced NSCLC patients as compared to chemotherapy except for irAEs.

Adverse Events of PD-1 or PD-L1 Inhibitors in Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

“…Campelo et al found that PD-L1 inhibitors were associated with a lower risk of adverse events that led to treatment discontinuation than PD-1 inhibitors [43]. The use of PD-1 or PD-L1 inhibitors significantly increased the risk of serious immune-related adverse events in this study [43], but the incidences were very low. Meanwhile, the risk of non-serious adverse events did not increase.…”

“…Sonpavde et al's study showed that the incidence of grade 3 or higher adverse events was higher in the PD-1 inhibitors group compared with PD-L1 inhibitors [42]. Campelo et al found that PD-L1 inhibitors were associated with a lower risk of adverse events that led to treatment discontinuation than PD-1 inhibitors [43]. The use of PD-1 or PD-L1 inhibitors significantly increased the risk of serious immune-related adverse events in this study [43], but the incidences were very low.…”

Expert consensus on perioperative treatment for non-small cell lung cancer

“…Nevertheless, targeted therapy and perioperative immunotherapy may be accompanied by serious AEs that can lead to delay or cancellation of surgery, additional illness, and even death. The severity of AEs can range from asymptomatic, severe, to life threatening ( 29 ).…”

The Chemokines Initiating and Maintaining Immune Hot Phenotype Are Prognostic in ICB of HNSCC

“…Application of immune checkpoint blockage (ICB) has significantly improved the prognosis of multiple tumors, but exerted limited effects on head and neck squamous cell carcinoma (HNSCC) because less than 30% of the patients got a better prognosis (Curran et al, 2010;Topalian et al, 2012;Seiwert et al, 2016;Clarke et al, 2021;García Campelo et al, 2021). To find out the HNSCC sub-populations susceptible to ICB therapy, various criteria have been proposed for HNSCC classification, by which HNSCC was classified into the enhanced and decreased immune subtypes with the immune-related genes (Cao et al, 2018), into the CD8 + high and CD8 + low subtypes with the density of infiltrating CD8 + T cells (Saloura et al, 2019), into the basal, mesenchymal, atypical, and classical subtypes with the integrated genomic characteristics (Walter et al, 2013), and even into the m6A high and m6A low subtypes with the N6methyladenosine (m6A) methylation levels on mRNAs (Yi et al, 2020).…”