ASSOCIATION OF ABLATIVE RADIOTHERAPY USE AND DURATION OF SYSTEMIC THERAPY IN PATIENTS WITH METASTATIC EGFR-MUTATED NON-SMALL CELL LUNG CANCER: A POPULATION-BASED ANALYSIS

Abstract

Purpose:

Advances in systemic therapy have improved survival for patients with EGFR-mutated non-small cell lung cancer (NSCLC). Randomized trials have shown that adding stereotactic body radiation therapy (SBRT) to EGFR-targeted tyrosine kinase inhibitors (TKIs) may improve progression-free survival (PFS) and overall survival (OS). Prospective studies also suggest that SBRT to oligoprogressive sites may prolong the duration of the same line of systemic therapy. This study evaluates these outcomes in a real-world setting using a population-based healthcare administrative database.

Materials and Methods:

We analyzed data from the provincial Institute for Clinical Evaluative Sciences (ICES), a repository of linked health administrative databases, identifying all patients diagnosed with non-squamous NSCLC between 2002 and 2022, in Ontario, Canada. Eligible patients received EGFR-targeted therapy with Gefitinib or Osimertinib, with treatment start/stop dates and radiotherapy (RT) data recorded. Patients younger than 18 or those with a prior cancer diagnosis within five years of NSCLC diagnosis were excluded. SBRT was defined as any radiotherapy course delivering ≥5 Gy per fraction in ≤8 fractions, except for single-fraction treatments ≤8 Gy. Patients who received SBRT during EGFR-targeted therapy were classified in the SBRT cohort, while all others comprised the palliative RT cohort. The primary outcome was the duration of first-line systemic therapy. Baseline and treatment characteristics were summarized descriptively, and OS was estimated via the Kaplan-Meier method from the date of drug start. Propensity score matching using logistic regression adjusted for baseline factors influencing systemic therapy duration, including age, sex, rurality index, Charlson and Elixhauser comorbidity indices, income quintile, and treatment year. A sensitivity analysis excluded patients treated before 2013 (~10% of the cohort).

Results:

A total of 898 patients met inclusion criteria, with 185 receiving SBRT and 713 receiving palliative RT. SBRT use increased in later years (2019-2022). The median duration of first-line systemic therapy was 683 days in the SBRT cohort versus 400 days in the palliative RT cohort (p<0.01). Median OS was 35.3 months (95% CI 27.2-77.5) for SBRT and 23.1 months (25.4-32.4) for palliative RT (p<0.01 log rank test). After excluding patients treated before 2013, 797 patients remained (SBRT: 171, palliative RT: 626). Median first-line systemic therapy duration was 692 versus 393 days, respectively (p<0.01), and median OS was 35.6 (95% CI 31.4-41.2) versus 23.1 months (95%CI 21.2-24.5) (p<0.01 log rank test). After propensity score matching (n=364, 184 per cohort), standardized mean differences were balanced (<0.1). The SBRT cohort maintained a longer median first-line therapy duration (683 versus 431 days, p<0.01) and improved median OS (35.3 versus 23.7 months) (p<0.01 log rank test).

Conclusions:

SBRT was associated with prolonged first-line systemic therapy duration and improved OS compared to palliative RT in Stage IV EGFR patients treated with targeted therapy. These findings remained consistent after propensity score matching and sensitivity analysis. SBRT may help extend the effective duration of systemic therapy in carefully selected patients.