6ER-048 Comparison of pembrolizumab + chemotherapy and nivolumab + ipilimumab + chemotherapy in metastatic squamous non-small-cell lung cancer with PD-L1 < 1%

<h3>Background and Importance</h3> First-line treatment for metastatic non-small-cell lung cancer (NSCLC) includes combinations based on immunotherapy and chemotherapy. Strategies involving nivolumab + ipilimumab (NIVO + IPI) and pembrolizumab (PEMBRO) can be considered alternatives with similar clinical benefit. However, they differ in management and toxicity, and have not been directly or indirectly compared. <h3>Aim and Objectives</h3> To evaluate the efficacy of PEMBRO and NIVO + IPI in patients with metastatic squamous NSCLC and PD-L1 &lt; 1%, based on subgroup analyses of pivotal clinical trials (CTs), and to assess the economic impact in our centre. <h3>Material and Methods</h3> Data from the KEYNOTE-407 (PEMBRO) and CHECKMATE-9LA (NIVO + IPI) clinical trials were analysed to identify differences in overall survival (OS) among subgroups of patients with squamous NSCLC and PD-L1 &lt; 1%. Interaction and indirect treatment comparison (ITC) adjusted analyses using Bucher’s method, were performed to determine whether the differences between treatments were statistically significant and clinically relevant. Additionally, the budgetary impact of both therapies was evaluated in our centre. <h3>Results</h3> No statistically significant interaction was observed among the three patient subgroups based on PD-L1 for PEMBRO (p = 0.37), nor for NIVO + IPI between squamous and non-squamous histologies (p = 0.19). Therefore, conducting an ICT exclusively with the PD-L1 &lt; 1% subgroup would not be methodologically appropriate. An ICT between NIVO + IPI and PEMBRO in squamous NSCLC, regardless of PD-L1 expression, showed no significant differences in OS (HR 0.90; 95% CI 0.65–1.26; p = 0.54). Similarly, although methodologically incorrect, an ICT for the PD-L1 &lt; 1% subgroup showed no significant differences (HR 0.80; 95% CI 0.53–1.20; p = 0.27). PEMBRO was more cost-effective, offering a 67% savings per patient compared to NIVO + IPI, according to current hospital pricing, translating to an annual savings of €62,407 in hospital expenses. <h3>Conclusion and Relevance</h3> Subgroup analyses do not demonstrate a superior clinical benefit of NIVO + IPI over PEMBRO in patients with squamous NSCLC and PD-L1 &lt; 1%. The apparent differences lack methodological validity and are attributable to chance. PEMBRO is the more cost-efficient option in our centre. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest