Continuation of epidermal growth factor receptor tyrosine kinase inhibitor treatment prolongs disease control in non-small-cell lung cancers with acquired resistance to EGFR tyrosine kinase inhibitors.

Qi Chen,Xiangchan Hong,Ningning Zhou,Lingyu Ding,Ying Liang,Qi Quan,Haiying Wu

doi:10.18632/oncotarget.4570

Qi Chen, Xiangchan Hong + Show 5 more

Open Access

https://doi.org/10.18632/oncotarget.4570

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Journal: Oncotarget	Publication Date: Jul 9, 2015
Citations: 38	License type: cc-by

Affiliation: Sun Yat-sen University Cancer Center

Abstract

Patients with non-small-cell lung cancer (NSCLC) develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) after tumor regression. No approved targeted therapies are currently available after initial EGFR TKI treatment. This study investigated the efficacy of continuing EGFR TKI therapy with local treatments for patients with NSCLC and local progression or minimal/slow progression on TKI therapy. Fifty-five patients with NSCLC treated with EGFR TKIs and developed acquired resistance to the drug were included. Initial response to target therapy, median progression free survival (PFS1), progression pattern, and first progression site were assessed. Median progression free survival to physician assessment progression (PFS2) and difference between PFS1 and PFS2 (PFS difference) were also recorded. PFS1 was 11.2 months, PFS2 was 20.3 months, and PFS difference was 8.3 months. Nineteen patients (34.5%) who manifested progression received local therapy, and 16 (28.6%) underwent rebiopsy after progression with six positive EGFR T790M mutations detected. Cox proportional hazards regression model showed that only the first line of treatment was significantly correlated with PFS difference. NSCLC patients with acquired resistance to EGFR TKIs could benefit from the same TKI therapy through months to years of disease control.

Highlights

IntroductionWe selected non-small-cell lung cancer (NSCLC) patients with local progression or minimal/slow progression on TKI therapy in our study
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are the standard of care in EGFR-mutant non-small-cell lung cancer because of its superior efficacy over chemotherapy. [1, 2] patients who initially responded to EGFR-TKIs would eventually present a median of 10–14 months in response evaluation criteria in solid tumors progressive disease (RECIST PD), [3,4,5] which clinically manifests as tumor progression and symptomatic decline
As no approved targeted therapies are currently available for patients with acquired resistance, they choose between standard cytotoxic chemotherapy with or without EGFR TKI continuation or enroll in clinical trials

Summary

Introduction

We selected NSCLC patients with local progression or minimal/slow progression on TKI therapy in our study. There is ongoing benefit from the targeted therapy in other sites of (non-progressing) disease due to continuing suppression of sensitive clones that have not yet developed acquired resistance. Ongoing prospective studies evaluate strategies of continuation of erlotinib beyond RECIST progression (ASPIRATION) [12] and gefitinib combined with chemotherapy beyond RECIST progression (IMPRESS); [13] results remain inconclusive. We designed this study to investigate the efficacy and safety of continuation of EGFR TKI therapy with necessary local treatments for NSCLC patients with local progression or minimal/ slow progression on TKI therapy. The potential factors that affect the effectiveness of this strategy were discussed

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Conclusion