Clinical Outcomes and Immune-Related Adverse Events in Metastatic Non-Squamous NSCLC Treated with First-Line Pembrolizumab–Chemotherapy: A Real-World Study from Serbia.
Simple Summary: Pembrolizumab combined with platinum-based chemotherapy is the standard first-line treatment for patients with metastatic non-squamous non-small-cell lung cancer (NSCLC) and intermediate PD-L1 expression (1–49%). However, treatment outcomes in routine clinical practice remain heterog...
| Published in: | Current Oncology Vol. 33; no. 5; pp. 267 - 281 |
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| Main Authors: | , , |
| Format: | Journal Article |
| Published: |
MDPI
May2026
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=194129139&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 194129139 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11980052 5EKK jtl: Current Oncology issn: 11980052 maglogo: N pubinfo: dt: May2026 vid: 33 iid: 5 pid: 97109 pub: MDPI artinfo: ui: 194129139 10.3390/curroncol33050267 194129139 ppf: 267 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Clinical Outcomes and Immune-Related Adverse Events in Metastatic Non-Squamous NSCLC Treated with First-Line Pembrolizumab–Chemotherapy: A Real-World Study from Serbia. aug: au: Bojić, Zlatan Marković, Filip Kontić, Milica affil: Clinic for Pulmonology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia sug: ab: Simple Summary: Pembrolizumab combined with platinum-based chemotherapy is the standard first-line treatment for patients with metastatic non-squamous non-small-cell lung cancer (NSCLC) and intermediate PD-L1 expression (1–49%). However, treatment outcomes in routine clinical practice remain heterogeneous, and predictors of benefit are not well defined. In this real-world study from Serbia, we evaluated clinical outcomes and immune-related adverse events (irAEs) in patients treated with first-line pembrolizumab–chemotherapy. We found that patients who developed skin or thyroid irAEs experienced longer progression-free survival. These findings suggest that certain low-grade, manageable immune toxicities may reflect effective immune activation and could serve as practical on-treatment markers of benefit in patients receiving chemo-immunotherapy. Background: Pembrolizumab combined with pemetrexed–platinum chemotherapy is the standard first-line treatment for patients with metastatic non-squamous non-small-cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) of 1–49%. Real-world data on treatment outcomes and the prognostic relevance of immune-related adverse events (irAEs) in this population remain limited, particularly in Eastern Europe. Methods: We conducted a retrospective, single-center real-world study including patients with metastatic non-squamous NSCLC and PD-L1 TPS of 1–49% treated with first-line pembrolizumab plus pemetrexed–platinum chemotherapy between June 2024 and May 2025. Progression-free survival (PFS) was estimated using the Kaplan–Meier method. Cox proportional hazards models were used to evaluate factors associated with PFS, including baseline clinical characteristics and organ-specific irAEs graded according to CTCAE v5.0. Results: A total of 107 patients were included. Median PFS for the entire cohort was 7.03 months (95% CI, 4.81–9.26). Immune-related adverse events occurred in 52 patients (48.6%), with thyroid (21.5%) and skin (13.1%) irAEs being the most frequent. The majority of irAEs were grade 1–2, while grade 3–4 events were rare (4.7%) and limited to hepatic toxicity and pneumonitis, all leading to treatment discontinuation. In multivariate analysis, ECOG performance status 2 was independently associated with inferior PFS (HR 3.09, 95% CI 1.74–5.48; p < 0.001). Conversely, the occurrence of thyroid irAEs (HR 0.36, 95% CI 0.17–0.78; p = 0.009) and skin irAEs (HR 0.28, 95% CI 0.10–0.79; p = 0.016) was independently associated with prolonged PFS, whereas pulmonary, hepatic, and gastrointestinal irAEs were not. Conclusions: In this real-world cohort of patients with metastatic non-squamous NSCLC treated with first-line pembrolizumab–chemotherapy, clinical outcomes were consistent with prior real-world experience. These findings suggest that low-grade, manageable immune toxicities may serve as pragmatic on-treatment markers of benefit. However, given the retrospective design, limited sample size, and the absence of time-dependent analyses, these associations should be interpreted with caution and considered hypothesis-generating rather than causal. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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