Impact of first-line immunotherapy on survival and intracranial outcomes in a cohort of non-small cell lung cancer patients with brain metastases at diagnosis
Menée en France dans un contexte de vie réelle à partir de données portant sur 118 patients atteints d'un cancer du poumon non à petites cellules et présentant des métastatases cérébrales lors du diagnostic (durée médiane de suivi : 30 mois), cette étude rétrospective compare l'efficacité, du point de vue de la survie globale et de la survie sans progression intra-crânienne, d'une immunothérapie et d'une chimiothérapie en traitement de première ligne
Background: Although brain metastases (BM) at diagnosis are common in non-squamous NSCLC patients (ns-NSCLC), they have been mostly excluded from randomized trials. The aim of this retrospective study was to evaluate real-word outcomes of frontline immune checkpoint inhibitor (ICI) in these patients. Methods: Our study assess the intracranial and overall efficacy of first-line ICI-based therapy compared to chemotherapy (CT) in ns-NSCLC patients diagnosed with BM, showing no targetable alterations. Patients were divided according to systemic therapy: CT, ICI, or CT-ICI. Primary endpoint was overall survival (OS), compared using Kaplan-Meier and Cox methodology. Secondary endpoint was intracranial progression free survival (icPFS). Results: Between 01-2018 and 05-2021, 118 patients were included (52 CT, 38 ICI and 28 CT-ICI). Median follow-up was 30.0 months. Intracranial radiotherapy was delivered for 75.0%, 68.4% and 67.9% of patients for CT, ICI and CT-ICI groups (p=0.805). After adjustment, ICI and CT-ICI were associated with a better OS compared to CT (HR=0.46, 95%CI: 0.23-0.89, and HR=0.52, 95%CI: 0.27-1.01, respectively). ICI and CT-ICI were associated with a significant reduction in the risk of intracranial progression by 54% (HR=0.46, 95%CI: 0.25–0.84) and 59% (HR=0.41, 95%CI: 0.23–0.77) compared to CT. Stereotactic radiosurgery was associated with an increased icPFS compared to systemic therapy alone (HR=0.51, 95% CI: 0.29 – 0.92), whereas whole-brain was not. Conclusions: Real-life ns-NSCLC patients with BM at diagnosis treated frontline with ICI presented OS and icPFS benefit compared to CT alone. A prospective assessment of the ideal type and sequence of systemic and local therapy should be conducted.