Universität zu Köln

Tan, Daniel S. W., Kim, Sang-We, Aix, Santiago Ponce, Sequist, Lecia, V, Smit, Egbert F., Yang, James C. H., Hida, Toyoaki, Toyozawa, Ryo, Felip, Enriqueta, Wolf, Juergen, Grohe, Christian, Leighl, Natasha B., Riely, Gregory, Cui, Xiaoming, Zou, Mike, Ghebremariam, Samson, O'Sullivan-Djentuh, Leslie, Belli, Riccardo, Giovannini, Monica and Kim, Dong-Wan (2022). Nazartinib for treatment-naive EGFR-mutant non-small cell lung cancer: Results of a phase 2, single-arm, open-label study. Eur. J. Cancer, 172. S. 276 - 287. OXFORD: ELSEVIER SCI LTD. ISSN 1879-0852

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Abstract

Introduction: Nazartinib, a novel third-generation EGFR-tyrosine kinase inhibitor, previously demonstrated antitumor activity and manageable safety in patients with EGFR-mut ant advanced non-small cell lung cancer (NSCLC) who received <= 3 prior lines of systemic ther-apy. Herein, we report phase 2 efficacy and safety of first-line nazartinib. Methods: 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. Results: 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). Conclusions: First-line nazartinib demonstrated promising efficacy, including clinically meaningful antitumor activity in the brain, and manageable safety in patients with EGFR-mutant NSCLC. (C) 2022 Published by Elsevier Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tan, Daniel S. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Sang-We UNSPECIFIED UNSPECIFIED UNSPECIFIED Aix, Santiago Ponce UNSPECIFIED UNSPECIFIED UNSPECIFIED Sequist, Lecia, V UNSPECIFIED UNSPECIFIED UNSPECIFIED Smit, Egbert F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, James C. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hida, Toyoaki UNSPECIFIED UNSPECIFIED UNSPECIFIED Toyozawa, Ryo UNSPECIFIED UNSPECIFIED UNSPECIFIED Felip, Enriqueta UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Grohe, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Leighl, Natasha B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riely, Gregory UNSPECIFIED UNSPECIFIED UNSPECIFIED Cui, Xiaoming UNSPECIFIED UNSPECIFIED UNSPECIFIED Zou, Mike UNSPECIFIED UNSPECIFIED UNSPECIFIED Ghebremariam, Samson UNSPECIFIED UNSPECIFIED UNSPECIFIED O'Sullivan-Djentuh, Leslie UNSPECIFIED UNSPECIFIED UNSPECIFIED Belli, Riccardo UNSPECIFIED UNSPECIFIED UNSPECIFIED Giovannini, Monica UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Dong-Wan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-696789
DOI:	10.1016/j.ejca.2022.05.023
Journal or Publication Title:	Eur. J. Cancer
Volume:	172
Page Range:	S. 276 - 287
Date:	2022
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1879-0852
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BRAIN METASTASES; RESISTANCE; OSIMERTINIB; MUTATIONS; FAILURE; CHEMOTHERAPY; INHIBITORS; GEFITINIB; EGF816; TKI Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69678