Pembrolizumab in the treatment of non-small cell lung cancer-experiences from clinical practice

Abstract

Background: Immune checkpoint inhibitors (ICIs) have become the standard first-line treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) without targetable mutations. This study aimed to assess real-world outcomes of pembrolizumab monotherapy in patients with high PD-L1 expression (≥50%) and compare them with results from the KEYNOTE-024 clinical trial.

Methods: This retrospective study included patients with advanced or metastatic NSCLC treated with pembrolizumab as first-line therapy at the Clinic for Pulmonary Diseases, University Clinical Center of Republika Srpska, between January 2018 and December 2022. Clinical and pathological data were collected from medical records and analyzed using descriptive and inferential statistical methods.

Results: The cohort included 46 patients with a median age of 64 years; 56.5% were aged ≥65, 73.9% were male, 76% were smokers, and 72% had an ECOG performance status of 1. Adenocarcinoma (AC) and squamous cell carcinoma (SCC) were diagnosed in 50 and 46% of cases, respectively, while 70% had metastatic disease and 15% had brain metastases. The two-year objective response rate (ORR) was 72.2%, lower than the 85.7% reported in KEYNOTE-024, possibly due to differences in PD-L1 assay (SP263 vs. 22C3) and patient selection. Despite this, the median overall survival (OS) was 36 months-higher than in the trial. One-, two-, and three-year survival rates were 57.9, 53.5, and 42.8%, respectively.

Conclusion: Our findings confirm the clinical benefit of pembrolizumab in a real-world setting, despite lower ORR compared to clinical trial data. However, the prognosis remains guarded due to the advanced stage and comorbidities of the population. Further investigation is warranted to optimize patient selection and treatment strategies.

Keywords: antibodies; carcinoma; immune checkpoint inhibitors; monoclonal; non-small-cell lung.

Figure 1

Kaplan–Meier curve of overall survival (OS) in patients with advanced NSCLC and high PD-L1 expression treated with first-line pembrolizumab—the solid line represents the OS probability over time, showing an initial decline (early mortality subset) followed by a plateau (longer survivors). The median OS was 36.0 months (95% CI: 12.3–59.7), and the mean OS was 33.5 months (95% CI: 26.3–40.8). Censored observations marked by + symbols, represent patients alive at last follow-up or lost to follow-up. The dotted line represents the 50% survival threshold.

Figure 2

Kaplan–Meier survival curves by gender—the overall mean survival time was 33.50 months (95% CI: 26.25–40.75). Women (blue line) showed a longer mean survival (43.36 months, 95% CI: 29.59–57.13) compared to men (red line; 30.19 months, 95% CI: 21.98–38.40). Median survival was 24 months for men (95% CI: 8.67–39.33) but could not be estimated for women due to high censoring (75% censored). The Log-Rank test indicated no statistically significant difference between groups (χ²(1) = 2.202, p = 0.138). Censored observations are marked with vertical ticks.

Figure 3

Kaplan–Meier survival curves by age group (<65 vs. ≥65 years)—patients aged ≥65 years (blue line) showed a non-significantly longer mean survival (35.15 months) compared to those <65 years (red line; 27.87 months). Median survival was 36.00 months for the <65 group but inestimable for ≥65 due to censoring (vertical ticks). The Log-Rank test confirmed no statistically significant difference (p = 0.567).

Figure 4

Kaplan–Meier survival curves by smoking status—current smokers (blue line) showed the shortest mean survival (28.51 months). Non-smokers (red line) demonstrated the longest mean survival (42.43 months), though median survival was inestimable due to censoring. Former smokers (green line) and unknown status (orange line) showed intermediate outcomes. Vertical ticks indicate censored cases. Log-Rank test revealed no statistically significant differences between groups (p = 0.132).

Figure 5

Kaplan–Meier survival curves by histologic subtype—patients with adenocarcinoma (blue line) showed the longest mean survival (34.73 months). Those with squamous cell carcinoma (red line) demonstrated intermediate outcomes (32.48 months), and patients with non-small cell lung cancer not otherwise specified (green line) had the poorest survival (25.50 months). Vertical ticks indicate censored cases. No statistically significant differences between groups (Log-Rank p = 0.953).