# The Progression Patterns and Subsequent Treatments of First‐Line Immunotherapy in Advanced Non‐Small Cell Lung Cancer: A Retrospective Cohort Study

## TL;DR

This study examines how advanced lung cancer patients respond to first-line immunotherapy and how their progression patterns affect survival and treatment outcomes.

## Contribution

The study identifies progression patterns and evaluates the effectiveness of subsequent immunotherapy treatments in real-world NSCLC patients.

## Key findings

- Most patients experienced systemic progression, with the lung being the most common site.
- Oligoprogression and progression in existing lesions were linked to better survival outcomes.
- Subsequent immunotherapy improved survival, especially in patients with systemic progression.

## Abstract

In metastatic non‐small cell lung cancer (NSCLC) patients receiving first‐line immune checkpoint inhibitors (ICIs), the real‐world progression patterns and subsequent treatment outcomes remain controversial.

We retrospectively analyzed patients with stage IV NSCLCs treated with first‐line immunotherapy between January 2017 and June 2023. Clinico‐demographic and treatment data were obtained from an electronic medical record system. Progression patterns were categorized by: (1) Progression in different organs; (2) Progression in existing or new lesions; and (3) Oligoprogression versus systemic progression. Survival was assessed using the Kaplan–Meier method and Cox proportional hazards models.

Among 157 patients, 67.5% experienced systemic progression, and 49.0% had progression in existing lesions. The most common organs with progression were the lung (81.5%), lymph nodes (35.0%), and pleural effusion (24.2%). Median post‐progression survival (PPS) was superior in oligoprogression versus systemic progression (22.4 vs. 10.9 months, p = 0.012). Patients with extrapulmonary progression (8.2 vs. 22.9 months, p < 0.001) or progression in new lesions (9.6 vs. 25.3 months, p = 0.029) showed decreased PPS. In multivariate Cox regression, ECOG PS of 2–4 (HR: 2.26, p = 0.003), tumor stage of IVB (HR: 1.74, p = 0.013), and extrapulmonary progression (HR: 2.05, p = 0.002) were associated with decreased PPS. Subsequent treatments containing ICIs improved survival compared to regimens without ICIs (29.0 vs. 11.3 months, p = 0.004), particularly in patients with systemic progression (19.3 vs. 9.2 months, p = 0.013).

Most metastatic NSCLCs on first‐line immunotherapy experienced systemic progression. Oligoprogression and progression only in existing lesions showed better prognoses, whereas extrapulmonary progression indicated worse survival. Subsequent ICI‐containing treatments had improved survival.

In patients with advanced NSCLCs receiving first‐line immunotherapy, most experienced systemic progression and had progression in existing lesions. Extrapulmonary progression was associated with decreased post‐progression survival, whereas oligoprogression and progression only in existing lesions showed better prognoses. After progression on first‐line immunotherapy, subsequent treatments with immunotherapy had improved survival, particularly in patients with systemic progression and acquired resistance.