Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter, open-label, randomized, controlled phase III trial

Zhenzhou Yang; Yan Zhang; Rongqing Li; Abulimiti Yisikandaer; Biyong Ren; Jianguo Sun; Jianjun Li; Long Chen; Ren Zhao; Juying Zhang; Xuefeng Xia; Zhongxing Liao; David P Carbone

doi:10.1093/neuonc/noaa281

Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter, open-label, randomized, controlled phase III trial

Neuro Oncol. 2021 Jun 1;23(6):967-978. doi: 10.1093/neuonc/noaa281.

Authors

Zhenzhou Yang^{1

2}, Yan Zhang³, Rongqing Li⁴, Abulimiti Yisikandaer⁵, Biyong Ren⁶, Jianguo Sun⁷, Jianjun Li⁸, Long Chen⁹, Ren Zhao¹⁰, Juying Zhang¹¹, Xuefeng Xia¹², Zhongxing Liao¹³, David P Carbone¹⁴

Affiliations

¹ Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² Cancer Center, Research Institute of Surgery, Daping Hospital, Chongqing, China.
³ Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
⁴ Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
⁵ Department of Radiotherapy of the Chest and Abdomen, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
⁶ Institute for Cancer Prevention and Treatment, Chongqing Sanxia Central Hospital, Chongqing, China.
⁷ Department of Medical Oncology, Xinqiao Hospital, Chongqing, China.
⁸ Department of Oncology, Southwest Hospital, Chongqing, China.
⁹ Department of Radiation Oncology, Cancer Hospital, Guangxi Medical University, Nanning, China.
¹⁰ Department of Radiotherapy, General Hospital of Ningxia Medical University, Yinchuan, China.
¹¹ Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
¹² GenePlus-Beijing Institute, Peking University Medical Industrial Park, Zhongguancun Life Science Park, Beijing, China.
¹³ Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹⁴ Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Medical Center, Columbus, Ohio, USA.

Abstract

Background: Erlotinib combined with whole-brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase II single-arm trial of non-small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase III, randomized trial.

Methods: NSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n = 115) or WBRT combined with erlotinib arms (n = 109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by the Mini-Mental State Examination (MMSE).

Results: A total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months vs 9.2 months for WBRT-alone (P = .601). Median PFS and overall survival (OS) of combination group were 5.3 vs 4.0 months (P = .825) and 12.9 vs 10.0 months (P = .545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 vs 12.8 months; P = .164), PFS (8.8 vs 6.4 months; P = .702), and OS (17.5 vs 16.9 months; P = .221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no significant differences in patients experiencing MMSE score change between the treatments.

Conclusion: Concurrent erlotinib with WBRT didn't improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases. Trial registration: Clinical trials.gov identifier: NCT01887795.

Keywords: brain metastases; epidermal growth factor receptor; erlotinib; non–small cell lung cancer; whole-brain radiation therapy.

Publication types

Clinical Trial, Phase III
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Brain
Brain Neoplasms* / therapy
Carcinoma, Non-Small-Cell Lung* / drug therapy
China
Cranial Irradiation
ErbB Receptors / genetics
Erlotinib Hydrochloride / therapeutic use
Humans
Lung Neoplasms* / therapy

Substances

Erlotinib Hydrochloride
ErbB Receptors

Associated data

ClinicalTrials.gov/NCT01887795