# Delay of Systemic Therapy Confers a Survival Benefit in Patients with Stage IV Non-Small-Cell Lung Cancer

## TL;DR

Starting systemic therapy later for advanced lung cancer patients is linked to longer survival, suggesting a benefit in delaying treatment.

## Contribution

The study shows that delaying systemic therapy in stage IV NSCLC improves survival, challenging the assumption that earlier treatment is always better.

## Key findings

- Delayed systemic therapy was associated with a median overall survival of 14 months versus 9 months for early therapy.
- The survival benefit of delayed therapy was consistent across age, metastasis, and ECOG subgroups.
- The findings suggest therapy timing may act as a confounder in clinical studies.

## Abstract

We wanted to know if the timepoint of a therapy for patients with incurable lung cancer influences their survival. We observed that a later beginning is associated with better survival. By investigating many subgroups, we could rule out typical errors, e.g., a worse survival that resulted from an earlier treatment of sicker patients. Our results are important for clinical studies and patient treatment.

Background: A timely systemic therapy of patients with metastasized non-small-cell lung cancer (NSCLC) is a suggestive clinical conception. As the pre-therapeutic management is complex and includes comprehensive immunohistochemical and molecular diagnostics, the time to optimal therapy may be prolonged. Whether the timing of therapy influences the outcome still remains controversial. We investigated the therapy timing and overall survival in subgroups of NSCLC patients in the clinical cancer registry of Lower Saxony. Materials and Methods: Patients with UICC stage IV NSCLC and systemic therapy were included. Early and delayed therapy groups based on the median time from histology to therapy were defined. Median overall survival (mOS) was estimated by the Kaplan–Meier test and compared by the log rank test. Uni- and multivariate Cox regression analyses were used for independent variables. Subgroup analyses were performed according to age, ECOG-PS, metastasis stage (M1a-c) and therapy. Results: We included 1687 patients; of these, the median age was 66.8 years, and 58% of patients were male. The median time to systemic therapy was 33 days, and in our sample, 844 patients were in the early and 843 in the delayed therapy group (TG). Median overall survival of the early TG patients was 9 m vs. 14 m in the delayed TG (p < 0.001). Subgroup analyses confirmed consistent findings among different age, metastasis and ECOG subgroups. Conclusions: UICC IV NSCLC patients with a delayed systemic therapy had a better overall survival than those with an early therapy. This observation supports a (qualified) waiting time for systemic therapies. Therapy timing may also be a relevant confounder in clinical studies.