| dc.contributor.author | Kelly, R. J. | |
| dc.contributor.author | Shepherd, F. A. | |
| dc.contributor.author | Krivoshik, A. | |
| dc.contributor.author | Jie, F. | |
| dc.contributor.author | Horn, L. | |
| dc.date.accessioned | 2020-08-27T19:53:24Z | |
| dc.date.available | 2020-08-27T19:53:24Z | |
| dc.date.issued | 2019-07 | |
| dc.identifier.citation | Kelly, R. J., Shepherd, F. A., Krivoshik, A., Jie, F., & Horn, L. (2019). A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer. Annals of oncology : official journal of the European Society for Medical Oncology, 30(7), 1127–1133. https://doi.org/10.1093/annonc/mdz128 | en_US |
| dc.identifier.issn | 0923-7534 | |
| dc.identifier.uri | http://hdl.handle.net/1803/15578 | |
| dc.description.abstract | Background 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.
Patients and methods This global, phase III, 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 end point was progression-free survival (PFS), and secondary end points included overall survival, investigator-assessed PFS, best overall response rate (ORR), disease control rate, duration of response (DoR), and the safety/tolerability profile.
Results 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 9.3months (95% CI 5.6-11.1months) for patients receiving ASP8273 and 9.6months (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 (9.2months for ASP8273 versus 9.0months for erlotinib/gefitinib). More grade >= 3 treatment-emergent adverse events (TEAEs) occurred in patients receiving ASP8273 than in those receiving erlotinib/gefitinib (54.7% versus 43.5%). An independent data monitoring committee carried out an interim safety analysis and recommended discontinuing the study due to toxicity and limited predicted efficacy of ASP8273 relative to erlotinib/gefitinib.
Conclusions First-line ASP8273 did not show improved PFS or equivalent toxicities versus erlotinib/gefitinib.
ClinicalTrial.gov number NCT02588261. | en_US |
| dc.description.sponsorship | This study was funded by Astellas Pharma, Inc. (Northbrook, IL; no grant number applicable). All authors had access to the study results, and the lead author vouches for the accuracy and completeness of the data reported. Financial support for the development of this manuscript was provided by the study sponsor. Writing and editorial assistance, provided by Stephan Lindsey, PhD, of OPEN Health Medical Communications (Chicago, IL) under the authors' guidance, was funded by the study sponsor (no grant number applicable for funding). | en_US |
| dc.language.iso | en_US | en_US |
| dc.publisher | Annals of Oncology | en_US |
| dc.rights | Copyright © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com | |
| dc.source.uri | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736319/ | |
| dc.subject | non-small-cell lung cancer | en_US |
| dc.subject | ASP8273 | en_US |
| dc.subject | EGFR inhibitor | en_US |
| dc.subject | phase III clinical trial | en_US |
| dc.title | A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer | en_US |
| dc.type | Article | en_US |
| dc.identifier.doi | 10.1093/annonc/mdz128 | |
