2SPD-005 Cemiplimab plus chemotherapy as first-line treatment in locally advanced or metastatic non-small-cell lung cancer in patients with PDL-1 expression ≥1%: comparison vs. current alternatives

<h3>Background and Importance</h3> Cemiplimab, combined with chemotherapy, is a promising first-line treatment for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with PDL-1 ≥1%. <h3>Aim and Objectives</h3> The aim of this study is to conduct a network meta-analysis (NMA) of therapies for locally advanced or metastatic non-small-cell lung cancer (NSCLC) inpatients with PDL-1 expression ≥1%, focusing on the efficacy and safety of cemiplimab in combination with chemotherapy compared to alternative first-line treatments. <h3>Material and Methods</h3> A systematic search was conducted on 6 June 2024, in PubMed to identify phase 3, randomised, double-blind, controlled clinical trials evaluating therapies for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) with PDL-1 expression ≥1%. The search strategy used the following terms: (Therapy/Narrow [filter]) AND (cemiplimab) AND (chemotherapy) AND (non-small-cell lung cancer). Studies were screened based on predefined inclusion criteria, which required reporting overall survival (OS) outcomes and relevance to the target population. Articles were excluded if they lacked sufficient survival data, focused on phase 1 or 2 trials, or did not meet quality standards for methodological rigour. A network meta-analysis (NMA) was performed using the netmeta package in R statistical software, employing a Bayesian framework and a common-effects model. In the NMA, all platinum-based chemotherapy regimens classified as equivalent according to the NCCN guidelines were grouped and treated as a single category to ensure consistency in comparisons. Hazard ratios (HR) were calculated to compare alternative therapies against cemiplimab combined with chemotherapy (cemiplimab_QT). <h3>Results</h3> The literature search yielded a total of seven studies that met the inclusion criteria. The overall survival analysis compared cemiplimab_QT with alternative therapies for patients with NSCLC. The results of the network meta-analysis were as follows: Atezolizumab_Bevacizumab_QT: HR = 1.38 (95% CI [0.96; 2.00]). Atezolizumab_QT: HR = 1.41 (95% CI [1.00; 1.99]). Durvalumab−Tremelimumab_QT: HR = 1.46 (95% CI [1.01; 2.11]). Nivolumab−Ipilimumab: HR = 1.48 (95% CI [1.06; 2.07]). Nivolumab−Ipilimumab_QT: HR = 1.35 (95% CI [0.93; 1.95]). Pembrolizumab_QT: HR = 1.22 (95% CI [0.87; 1.72]). Platinum-based chemotherapy: HR = 1.92 (95% CI [1.44; 2.58]). <h3>Conclusion and Relevance</h3> The results highlight that, compared to durvalumab-tremelimumab and nivolumab-ipilimumab, Cemiplimab achieved a more favourable overall survival, especially when compared to platinum-based chemotherapy, which had the highest risk of death (HR =1.92). <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest