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.
Highlights
Literature search terms used were “non-small cell lung cancer”, “programmed deathligand 1 (PD-L1)”, “programmed cell death-1 receptor (PD-1)”, “pembrolizumab”, “nivolumab”, “atezolizumab”, “durvalumab”, “cemiplimab”, and all terms related to clinical trial registration
The MA of the as-treated populations from the six phase III randomized clinical trials (RCTs) included in our study, revealed a statistically significant reduced risk of any grade trAEs for immuno-therapy versus chemotherapy (RR = 0.722 95%confidence intervals (CIs): 0.667, 0.783, p < 0.001; Figure 2A)
adverse events (AEs) to treatment in patientsintreated with anti-PD-1 or anti-PD-L1 immunotherapy compared to platinum-based leading todiscontinuation treatment discontinuation patients treated with anti-PD-1 or anti-PD-L1 immunotherapy compared to platinum-based chemotherapy
Summary
Chemotherapy has been the therapeutic strategy available for lung cancer [5]; in recent years, the introduction of novel agents and the use of predictive biomarkers have resulted in improved outcomes for patients with advanced/metastatic. Anti-PD-L1 monotherapy resulted in significantly longer overall survival and progression free survival in advanced NSCLC patients with high PD-L1 expression compared to chemotherapy alone, supporting the potential of this therapeutic option as a first-line strategy for this subgroup of patients [9]. We performed a NMA to evaluate the safety of first-line PD-L1 inhibitors monotherapy in advanced NSCLC positive PD-L1 patients compared to platinum-based chemotherapy. We carried out indirect comparisons between immunotherapies to assess the potentially differential risk of clinically relevant immune-related AEs (irAEs)
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