Thoracic radiotherapy and concurrent almonertinib for unresectable stage III EGFR-mutated non-small-cell lung cancer: a phase 2 study

Lucheng Zhu, Changlin Zou, Zhanchun Zhang, Jianfang Wang, Li Yang, Chuangzhou Rao, Zhiping Yang, Jiafeng Liang, Bing Xia, M A Shenglin, Lucheng Zhu, Changlin Zou, Zhanchun Zhang, Jianfang Wang, Li Yang, Chuangzhou Rao, Zhiping Yang, Jiafeng Liang, Bing Xia, M A Shenglin

Abstract

Background: Concurrent chemo-radiotherapy remains the standard treatment in unresectable stage III non-small-cell lung cancer (NSCLC) patients. Several studies have shown a potential value of concurrent epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with thoracic radiotherapy in EGFR-mutated population, but a high risk of radiation pneumonitis raised a major concern. This study intends to explore the safety and efficacy of concurrent almonertinib, a new third-generation EGFR-TKI, with radiotherapy in locally advanced EGFR-mutated NSCLC patients.

Methods: Locally advanced NSCLC patients harboring sensitive EGFR mutation will be included in this study. A radiotherapy plan will be made for each patient before treatment, and the lung V20 will be calculated. Patients with lung V20 ≥ 28% were enrolled in induction group (arm A), which almonertinib was given for 2 months followed by concurrent radiotherapy; patients with lung V20 < 28% were enrolled in concurrent group (arm B), which almonertinib was given concurrent with thoracic radiotherapy. The primary endpoint is the incidence of grade ≥ 3 radiation pneumonitis within 6 months post-radiotherapy, and the secondary endpoints are local control rate, progression-free survival, and overall survival.

Discussion: The safety and efficacy of third-generation EGFR-TKI concurrent with thoracic radiotherapy in locally advanced EGFR-mutated NSCLC is still unknown. We propose to conduct this phase 2 study evaluating the safety especially the radiation pneumonitis within 6 months post-radiotherapy. This trial protocol has been approved by the Ethics committee of Hangzhou cancer hospital. The ethics number is HZCH-2020-030.

Trial registration: clinicaltrials.gov, NCT04636593 . Registered 19 November 2020 - Retrospectively registered.

Keywords: Almonertinib; EGFR-TKI; Locally advanced NSCLC; Radiation pneumonitis; Radiotherapy.

Conflict of interest statement

The authors have stated that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Scheme of the study

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