Central nervous system efficacy of Rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: a pooled analysis of two clinical studies
Menée à partir des données de deux essais cliniques incluant un total de 335 patients atteints d'un cancer du poumon non à petites cellules avec mutation T790M au niveau du gène EGFR et présentant des métastases au niveau du système nerveux central, cette étude évalue l'efficacité, notamment du point de vue du taux de réponse objective et du taux de contrôle de la maladie mesurés au niveau du système nerveux central, du rézivertinib, un inhibiteur de tyrosine kinase de l'EGFR de troisième génération
Background: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here. Methods: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (≥180mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated. Results: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. At the data cutoff dates, the CNS-ORR was 32% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were 52.0% (range: -16.1-100%) and 46.8% (95% CI: 38.1-55.5%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95%CI: 13.7-NC) months. Conclusions: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.