Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated NSCLC
Mené entre 2016 et 2019 sur 133 patients atteints d'un cancer du poumon non à petites cellules oligométastatique et présentant une mutation de l'EGFR (durée médiane de suivi : 23,6 mois), cet essai randomisé de phase III évalue l'intérêt, du point de vue de la survie sans progression, d'ajouter une radiothérapie à un traitement systémique par inhibiteur de la tyrosine kinase
Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to EGFR-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC, and randomized to up-front RT vs. no RT; we now report the pre-specified interim analysis at 68% accrual.Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly-diagnosed, treatment-naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs. RT (25–40 Gy in 5 fractions depending on tumor size/location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention-to-treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided.A total of 133 patients (n = 65 TKI only, n = 68 TKI+RT) were enrolled (2016–2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs. 20.2 months (p < .001), and the median OS was 17.4 months vs. 25.5 months (p < .001) for TKI only vs TKI+RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3–4 pneumonitis in the TKI+RT arm. Based on the efficacy results of this pre-specified interim analysis, the ethics committee recommended premature cessation of this trial.As compared to a first-line TKI alone, addition of up-front local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.
Journal of the National Cancer Institute , article en libre accès, 2021