Pembrolizumab versus Pembrolizumab plus Chemotherapy in Non-small Cell Lung Cancer with High PD-L1 Expression - Multicenter Real-world Evidence Study.

Patients with non-small cell lung cancer (NSCLC) with PD-L1 expression ≥ 50% can be treated with immunotherapy alone or with a combination of immunotherapy and chemotherapy. One of these options is treatment with pembrolizumab (P) with/without chemotherapy (CHT). Meta-analyses from randomized trials suggest a beneficial effect on response rate (RR) or progression free survival (PFS) when using the combination treatment P + CHT compared to P alone, but not on improving overall survival (OS). However, data from real-world clinical practice are insufficient especially in European patients. Regional differences, e.g. in the representation of KRAS mutations between Asian and European patients, could theoretically influence potential differences between P + CHT and P. Therefore, the aim of this study was to compare P + CHT versus P alone in real clinical practice in patients from Central Europe. Retrospective data from 8 comprehensive oncology centres in Central Europe were used. All patients with PD-L1 expression ≥ 50% with stage IV NSCLC treated with pembrolizumab in daily practice to June 2024 were included and their data statistically analysed. In the whole group 793 patients was included in the study - 706 treated with P and 87 with P+ CHT. In this unadjusted sample, we observed significantly higher RR (p <0.0001) and OS (p = 0.044) for the P + CHT group vs. P. For significant differences in both groups, where performance status in particular played a role in survival in the Cox model, we subsequently performed patient matching 2 (P+CHT):1 (P) from the whole group of patients. After this patient matching, we continued to observe a significant difference in RR (p = 0.005), but no longer in OS (p = 0.103). The PFS was not significantly different in both cases (p= 0.174 for unadjusted patients resp. p = 0.342 for matching groups). P+CHT leads to a significantly higher RR compared to P and can therefore be considered in patients with a more certain treatment response goal (e.g., bulky symptomatic tumor), however, this advantage does not translate into PFS and OS benefit.