Introduction: Elderly patients with metastatic non-small-cell lung cancer (NSCLC) are underrepresented in clinical trials evaluating immune checkpoint inhibitors (ICIs). This study assesses the efficacy of first-line pembrolizumab monotherapy in patients with metastatic NSCLC aged ≥70 years with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50%. Materials and Methods: We retrospectively analyzed 381 patients with metastatic NSCLC without oncogenic driver mutations treated with pembrolizumab monotherapy between 2017 and 2023 at three academic centers in Central and Southeastern Europe. Clinical outcomes, including median time on treatment (mToT) and overall survival (mOS), were compared between patients aged ≥70 and <70 years. Results: Of 381 patients, 149 (39.1%) were aged ≥70. No significant differences in mToT (12.7 vs. 14.3 months; p = 0.125) or mOS (18.2 vs. 27.4 months; p = 0.124) were observed between older and younger groups. Good ECOG PS (0–1) was independently associated with longer mToT and mOS in older patients. Additionally, a history of smoking was linked to improved outcomes compared to never-smokers, suggesting potential immunogenic effects. Older patients were significantly less likely to receive second-line therapy after progression (p = 0.04). Conclusions: First-line pembrolizumab monotherapy is effective across all age groups and provides similar treatment efficacy in patients with metastatic NSCLC and a PD-L1 TPS ≥ 50%. Patients older than 70 with a smoking history and ECOG PS 0–1 derive the most benefit from this treatment modality. The adaptation of this treatment strategy for elderly patients is especially important, since only a minority of them are capable of receiving second-line therapy.

Background: Non-small cell lung cancer (NSCLC), particularly in advanced stages, has poor prognosis. The main objective of the study is to evaluate real-world treatment outcomes in advanced NSCLC patients harboring an EGFR mutation and being treated with TKIs. Methods: The EGFR mutation status was ascertained by next-generation sequencing. The observational cohort study used prospectively maintained registry data. Patient data were collected at two high-volume institutions in Austria between November 2020 and February 2025. The prevalence of EGFR mutations was 11% (145 out of 1267 patients). Results: Among 53 patients (stage IIIB or higher) with an EGFR mutation, median overall survival (OS) and median progression-free survival (PFS) were 17.7 months (95% CI: 10.4–24.9) and 14.2 months (95% CI: 7.4–20.9), respectively. A total of 36 patients harbored common EGFR mutations (exon 19 deletion or L858R point mutation) and exhibited a significantly better OS than those with an uncommon EGFR genotype (p < 0.005). Patients with exon 19 deletion (n = 25) showed the longest mOS, followed by those with L858R mutation (32.5 vs. 17 months). In multivariable analysis, the EGFR common mutation subtype (HR = 3.71 95%CI: 1.23–11.2) was associated with better OS. Patients with common EGFR genotypes, especially exon 19 deletion obtained longer OS and PFS compared with those with uncommon mutations in exon 18–21. Conclusions: The results underscore the prognostic role of distinct EGFR genotypes and the urgency of determining the mutation status in non-small cell lung cancer patients to ensure the best treatment decision. The study also highlights the challenges regarding to EGFR uncommon mutations and the resulting need for further research to investigate alternative treatment options.

Background: Non-small cell lung cancer (NSCLC), particularly in advanced stages, has poor prognosis. The main objective of the study is to evaluate real-world treatment outcomes in advanced NSCLC patients harboring an EGFR mutation and being treated with TKIs. Methods: The EGFR mutation status was ascertained by next-generation sequencing. The observational cohort study used prospectively maintained registry data. Patient data were collected at two high-volume institutions in Austria between November 2020 and February 2025. The prevalence EGFR mutations was 11% (145 out of 1,267 patients). Results: Among 53 patients (stage IIIB or higher) with an EGFR mutation, median overall survival (OS) and median progression-free survival (PFS) were 17.7 months (95% CI: 10.4-24.9) and 14.2 months (95% CI: 7.4-20.9), respectively. A total of 36 patients harbored common EGFR mutations (exon 19 deletion or L858R point mutation) and exhibited a significantly better OS than those with an uncommon EGFR genotype (p < 0.005). Patients with exon 19 deletion (n = 25) showed the longest mOS, followed by those with L858R mutation (32.5 vs. 17 months). In multivariable analysis, EGFR common mutation subtype (HR = 3.71 95%CI: 1.23 – 11.2) was associated with better OS. Patients with common EGFR genotypes, especially exon 19 deletion obtained longer OS and PFS compared with those with uncommon mutations in exon 18-21. Conclusion: The results underscore the prognostic role of distinct EGFR genotypes and the urgency to determine the mutation status in non-small cell lung cancer patients to ensure the best treatment decision. The study also highlights the challenges regarding to EGFR uncommon mu-tations and the resulting need for further research to investigate alternative treatment options.

Background: ALK-rearranged non-small cell lung cancer (NSCLC) is a molecularly defined subtype that is highly sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors). With multiple generations of ALK inhibitors available, real-world data on treatment patterns and sequencing in routine clinical practice remain limited. Methods: This retrospective multicenter registry analysis included patients with ALK-positive NSCLC treated with palliative intent and enrolled in the LALUCA registry between November 2020 and September 2025 at four lung cancer centers in Vienna. ALK alterations were confirmed by next-generation sequencing. Demographic, clinical, and treatment-related data were analyzed descriptively. Results: Twenty-eight patients were included (median age, 54 years [range, 26–84]; 46.4% female). Most patients had stage IV disease (85.7%) and adenocarcinoma histology (92.9%). Overall, 49 systemic treatment lines were administered, including 41 ALK inhibitor treatment lines (22 second-generation and 19 third-generation). At data cut-off, 39.0% of ALK inhibitor treatment lines were ongoing, with a higher proportion of ongoing treatment observed among third-generation compared with second-generation ALK inhibitors (52.6% vs. 27.3%). The Kaplan–Meier-estimated median treatment duration was 287 days (95% CI, 172-NE) for second-generation and 736 days (95% CI, 376–NE) for third-generation ALK inhibitors. Objective response rates were 77.3% and 73.7%, respectively. Adverse events of any grade occurred in 73.2% of treatment lines, while grade ≥ 3 adverse events occurred in 12.2%. Dose reductions and temporary treatment interruptions were used to manage toxicity and allowed for treatment continuation in most affected treatment lines. Conclusions: This multicenter real-world analysis provides insights into contemporary ALK inhibitor treatment patterns and sequencing in routine clinical practice. Third-generation ALK inhibitors were associated with longer observed treatment durations in this cohort, although these findings should be interpreted cautiously given the small sample size, retrospective analysis, and potential differences in treatment selection and follow-up. Overall, toxicity was generally manageable, with dose modifications and temporary treatment interruptions frequently allowing for continuation of ALK inhibitor therapy.