A Phase 3, Randomized, Open-label Study of ASP8273 Versus Erlotinib or Gefitinib in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Cancer
Mené sur 530 patients atteints d'un cancer du poumon non à petites cellules de stade avancé et présentant des mutations EGFR, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un composé appelé ASP827 (un inhibiteur irréversible de tyrosine kinase) et de l'erlotinib ou du géfitinib en traitement de première ligne
ASP8273, a novel, small molecule, irreversible tyrosine kinase inhibitor (TKI) specifically inhibits the epidermal growth factor receptor (EGFR) in patients with activating mutations or EGFR T790M resistance mutations. The current study examines the efficacy, safety, and tolerability of ASP8273 versus erlotinib or gefitinib in patients with non-small cell lung cancer (NSCLC) with activating EGFR mutations not previously treated with an EGFR inhibitor.This global, phase 3, open-label, randomized study evaluated ASP8273 versus erlotinib/gefitinib in patients with locally advanced, metastatic, or unresectable stage IIIB/IV NSCLC with activating EGFR mutations. They were ineligible if they received prior chemotherapy for metastatic disease. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival, investigator-assessed PFS, best overall response rate (ORR), disease control rate, duration of response (DoR), and the safety/tolerability profile.Patients (n=530) were randomized 1:1 to receive ASP8273 (n=267) or erlotinib/gefitinib (n=263). Patient demographics between both treatment groups were generally balanced. Median PFS was 9.3 months (95% CI, 5.6–11.1 months) for patients receiving ASP8273 and 9.6 months (95% CI, 8.8–NE) for the erlotinib/gefitinib group, with a hazard ratio of 1.611 (P=0.992). The ORR in the ASP8273 group was 33% (95% CI, 27.4–39.0) versus 47.9% (95% CI, 41.7–54.1) in the erlotinib/gefitinib group. Median DoR was similar for both groups (9.2 months for ASP8273 vs 9.0 months for erlotinib/gefitinib). More grade ≥3 treatment-emergent adverse events (TEAEs) occurred in patients receiving ASP8273 than in those receiving erlotinib/gefitinib (54.7% vs 43.5%). An independent data monitoring committee performed an interim safety analysis and recommended discontinuing the study due to toxicity and limited predicted efficacy of ASP8273 relative to erlotinib/gefitinib.First-line ASP8273 did not show improved PFS or equivalent toxicities versus erlotinib/gefitinib.NCT02588261.
Annals of Oncology 2019