DURATION OF SYSTEMIC THERAPY IN PATIENTS WITH METASTATIC EGFR-MUTATED NSCLC AND BRAIN METASTASES: FIRST VERSUS THIRD GENERATION TKIS

Abstract

Purpose:

New-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as Osimertinib, demonstrate high central nervous system (CNS) activity in EGFR-mutated non-small cell lung cancer (NSCLC). Clinical guidelines recommend TKI monotherapy as an effective option for small, asymptomatic brain metastases (BM). We hypothesize that patients receiving Osimertinib remain on therapy longer than those on first- or second-generation TKIs. This study evaluates treatment duration in a real-world setting using a healthcare administrative database.

Materials and Methods:

We analyzed data from the Institute for Clinical Evaluative Sciences (ICES), a provincial health administrative database, identifying patients diagnosed with non-squamous NSCLC from 2002 to 2022. Eligible patients received first-line EGFR-targeted therapy with either Gefitinib or Osimertinib. Brain radiotherapy receipt was used as a surrogate for BM presence. Patients under 18 or those with a prior cancer diagnosis within five years were excluded. The primary outcome was the duration of first-line systemic therapy. Overall survival (OS) was estimated using the Kaplan-Meier method. Propensity score matching adjusted for baseline factors influencing systemic therapy duration, including age, sex, rurality index, Charlson and Elixhauser comorbidity indices, income quintile, and treatment year.

Results:

Among 3,088 screened patients with EGFR-mutated NSCLC, 1,243 received Osimertinib and 1,845 received Gefitinib as first-line therapy. A total of 761 patients had BM and met inclusion criteria (Osimertinib: 308; Gefitinib: 453). The median first-line systemic therapy duration was significantly longer in the Osimertinib cohort (327 versus 190 days, p<0.001). Median OS was also higher with Osimertinib (21.8 versus 14.0 months, p<0.001). After propensity score matching (n=168, 84 in each cohort), patients on Osimertinib first line had a median duration of 390 days versus 154 days per patients receiving Gefitinib. There was no longer a significant difference in OS, with a median OS of 16.2m versus 14.7m in the same respective cohorts (p=0.36).

Conclusions:

Patient with brain metastases treated with Osimertinib remained on this line of systemic therapy longer than patients treated with Gefitinib. These findings remained consistent after propensity score matching. These findings suggest that despite BM, patients on Osimertinib may have sustained efficacy in this patient population.