Concurrent EGFR-TKI and Thoracic Radiotherapy as First-Line Treatment for Stage IV Non-Small Cell Lung Cancer Harboring EGFR Active Mutations

LinPeng Zheng, Yanmei Wang, Zihan Xu, Qiao Yang, Guangkuo Zhu, Xing-Yun Liao, Xiewan Chen, Bo Zhu, Yuzhong Duan, Jianguo Sun, LinPeng Zheng, Yanmei Wang, Zihan Xu, Qiao Yang, Guangkuo Zhu, Xing-Yun Liao, Xiewan Chen, Bo Zhu, Yuzhong Duan, Jianguo Sun

Abstract

Lessons learned: This single-arm, phase II study shows that concurrent EGFR-tyrosine kinase inhibitor plus thoracic radiotherapy as the first-line treatment for stage IV non-small cell lung cancer harboring EGFR active mutations provides long-term control for the primary lung lesion, and 1-year progression-free survival (PFS) rate and median PFS are numerically higher than those of the erlotinib monotherapy.Serious adverse events are acceptable, although grade >3 radiation pneumonitis occurred in 20% of patients.

Background: Studies show effective local control by EGFR-tyrosine kinase inhibitor (TKI) combined with radiotherapy at metastatic sites in advanced lung cancer harboring EGFR active mutations. Salvage local radiotherapy is associated with prolonged progression-free survival (PFS) in local disease during EGFR-TKI treatment. However, no prospective study has been reported on concurrent EGFR-TKI and radiotherapy for primary lung lesions. This study investigated the efficacy and safety of first-line EGFR-TKI combined with thoracic radiotherapy in treating stage IV non-small cell lung cancer (NSCLC) harboring EGFR active mutations.

Methods: We conducted a single-arm, phase II clinical trial. Each patient received EGFR-TKI (erlotinib 150 mg or gefitinib 250 mg per day) plus thoracic radiotherapy (54-60 Gy/27-30 F/5.5-6 w) within 2 weeks of beginning EGFR-TKI therapy until either disease progression or intolerable adverse events (AEs) appeared.

Results: From January 2015 to March 2018, 401 patients were screened, and 10 patients (5 male and 5 female) were eligible. These patients had a median age of 55 years (40-75) and median follow-up of 19.8 months (5.8-34). The 1-year PFS rate was 57.1%, median PFS was 13 months, and median time to progression of irradiated lesion (iTTP) was 20.5 months. Objective response rate (ORR), was 50% and disease control rate (DCR) was 100%. The most common grade ≥3 AEs were radiation pneumonitis (20%) and rash (10%). One patient died after rejecting treatment for pneumonitis. The others received a full, systematic course of glucocorticoid therapy. Pneumonitis was all well controlled and did not relapse.

Conclusion: Concurrent EGFR-TKI plus thoracic radiotherapy as the first-line treatment for stage IV NSCLC harboring EGFR active mutations shows a long-term control of primary lung lesion. The 1-year PFS rate and median PFS of this combined therapy are numerically higher than those of the erlotinib monotherapy. The risk of serious adverse events is acceptable.

Trial registration: ClinicalTrials.gov NCT02353741.

© AlphaMed Press; the data published online to support this summary are the property of the authors.

Figures

Figure 2.
Figure 2.
Tumor response. (A): Spider plot of dynamic changes in the maximum diameter of the tumor. (B): Best tumor response. (C): Compared with the ENSURE study, there was no significant difference in ORR (50%, p = .43) or DCR (100%, p = .27). ORR = CR + PR; local control rate = CR + PR + SD. Abbreviations: CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease; TKI, tyrosine kinase inhibitor; TRT, thoracic radiotherapy.
Figure 3.
Figure 3.
Flow chart of patient enrollment process. Abbreviations: NSCLC, non‐small cell lung cancer; TKI, tyrosine kinase inhibitor.
Figure 1.
Figure 1.
Progression‐free survival. Abbreviation: PFS, progression‐free survival.

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