# PD-L1 Negative Advanced Non-Small Cell Lung Cancer: Practice Patterns and Real-World Outcomes

## TL;DR

This study examines treatment patterns and outcomes for PD-L1 negative advanced lung cancer patients, finding no significant survival benefit from combining immunotherapy with chemotherapy in real-world settings.

## Contribution

The study provides real-world evidence on treatment outcomes for PD-L1 negative NSCLC patients, highlighting discrepancies between clinical trials and practice.

## Key findings

- Combining immunotherapy with chemotherapy did not significantly improve survival compared to chemotherapy alone in this cohort.
- Treatment tolerance was consistent with clinical trial reports, but survival outcomes were more modest in real-world settings.
- Immune-related adverse events occurred in nearly 30% of patients receiving combination therapy.

## Abstract

For patients with advanced non-small cell lung cancer whose tumors do not express PD-L1, treatment often combines chemotherapy with immunotherapy. Although clinical trials suggest this approach can improve survival compared to chemotherapy alone, outcomes appear more modest in the real-world setting. We reviewed practice patterns and survival outcomes of patients treated at a Canadian academic center over five years. We found that, in our cohort, adding immunotherapy to chemotherapy did not significantly improve survival compared with chemotherapy alone, likely due to insufficient statistical power. However, tolerance to treatment was similar to that reported in clinical trials. The limited number of patients in our study, the broader eligibility criteria used in real-world practice, and the fact that some medically fit patients declined combination treatment may explain these results. These findings suggest that clinical trial results may not fully reflect real-world populations and highlight the need for better tools to support treatment decisions and patient discussions.

The standard first-line treatment for metastatic non-small cell lung cancer (NSCLC) without oncogenic alterations and programmed death-ligand 1 (PD-L1) expression < 1% is a combination of chemotherapy (CT) and immunotherapy (IO). However, real-world overall survival (OS) appears more modest than in clinical trials, averaging 10–13 months. This retrospective study aimed to assess treatment patterns and real-world outcomes at the Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ). Patients diagnosed between January 2019 and December 2023 with advanced PD-L1 <1% NSCLC and treated with palliative intent at IUCPQ were included and categorized by first-line treatment. Progression-free survival (PFS) and OS of the CT + IO and CT groups were compared using Kaplan–Meier curves and Cox regression analyses. Data regarding regimen selection, adverse events and subsequent treatment lines were collected. Among 217 eligible patients, 82 (37.8%) received CT + IO, 32 (14.7%) CT alone, 16 (7.4%) targeted therapy, and 87 (40.1%) supportive care. Median PFS was 5.3 vs. 4.7 months (p = 0.5) and OS 14.4 vs. 13.5 months (p = 0.2) for CT + IO and CT alone, respectively. In the CT + IO group, treatment discontinuation was mainly due to disease progression (59.4%) or adverse events (36.2%). Immune-related adverse events occurred in 29.3%, most frequently pneumonitis (8.5%). Therefore, in this cohort, no statistically significant survival difference was observed between CT + IO and CT alone. However, these findings should be interpreted cautiously given the non-randomized design, baseline imbalances between groups, and the limited sample size of the CT alone cohort. Tolerability of CT + IO was consistent with that observed in clinical trials.