학술논문
Nazartinib for treatment-naive EGFR-mutant non−small cell lung cancer: Results of a phase 2, single-arm, open-label study.
Document Type
Article
Author
Tan, Daniel S.W.; Kim, Sang-We; Ponce Aix, Santiago; Sequist, Lecia V.; Smit, Egbert F.; Yang, James C.H.; Hida, Toyoaki; Toyozawa, Ryo; Felip, Enriqueta; Wolf, Juergen; Grohé, Christian; Leighl, Natasha B.; Riely, Gregory; Cui, Xiaoming; Zou, Mike; Ghebremariam, Samson; O'Sullivan-Djentuh, Leslie; Belli, Riccardo; Giovannini, Monica; Kim, Dong-Wan
Source
Subject
*LUNG cancer
*DISEASE progression
*CONFIDENCE intervals
*CLINICAL drug trials
*HETEROCYCLIC compounds
*EPIDERMAL growth factor receptors
*ANTINEOPLASTIC agents
*PROTEIN-tyrosine kinase inhibitors
*PROGRESSION-free survival
*PATIENT safety
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Language
ISSN
0959-8049
Abstract
Nazartinib, a novel third-generation EGFR-tyrosine kinase inhibitor, previously demonstrated antitumor activity and manageable safety in patients with EGFR -mutant advanced non−small cell lung cancer (NSCLC) who received ≤ 3 prior lines of systemic therapy. Herein, we report phase 2 efficacy and safety of first-line nazartinib. This single-arm, open-label, global study enrolled treatment-naive adult patients with stage IIIB/IV NSCLC harboring EGFR -activating mutations (eg, L858R and/or ex19del). Patients with neurologically stable and controlled brain metastases were also eligible. Patients received oral nazartinib 150 mg once daily. The primary endpoint was Blinded Independent Review Committee (BIRC)-assessed overall response rate (ORR) per RECIST v1.1. Forty-five patients received ≥ 1 dose of nazartinib. The median follow-up time from enrollment to data cutoff (November 1, 2019) was 30 months (range: 25–34). The BIRC-assessed ORR was 69% (95% CI, 53–82). The median progression-free survival (PFS) was 18 months (95% CI, 15-not estimable [NE]). The median overall survival was NE. In patients with baseline brain metastases (n = 18), the ORR and median PFS (95% CIs) were 67% (41–87) and 17 months (11–21). Seventeen of 18 patients had brain metastases as non-target lesions; the CNS lesions were absent/normalized in 9 of 17 (53%). Only 2 of 27 patients without baseline brain metastases developed new brain metastases postbaseline. Most frequent adverse events (≥ 25%, any grade, all-causality) were diarrhea (47%), maculopapular rash (38%), pyrexia (29%), cough, and stomatitis (27% each). First-line nazartinib demonstrated promising efficacy, including clinically meaningful antitumor activity in the brain, and manageable safety in patients with EGFR -mutant NSCLC. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02108964. • Nazartinib is a novel third-generation EGFR tyrosine kinase inhibitor. • First-line nazartinib was evaluated in patients with advanced EGFR -mutant NSCLC. • Nazartinib showed promising efficacy, including antitumor activity in the brain. • The safety profile of nazartinib was manageable. • Results support further development of nazartinib for advanced EGFR -mutant NSCLC. [ABSTRACT FROM AUTHOR]