Exploration on the first-line treatment of ERBB2-altered advanced non-small cell lung cancer: A multicenter retrospective study

Jiayan Chen; Chunwei Xu; Qian Wang; Jiawen Lv; Wanjun Lu; Yixue Zhang; Yanwen Yao; Xiaoling Gu; Guannan Wu; Yue Hao; Weiwei Pan; Wenxian Wang; Shirong Zhang; Tangfeng Lv; Yong Song; Dong Wang

doi:10.1016/j.lungcan.2023.107315

Exploration on the first-line treatment of ERBB2-altered advanced non-small cell lung cancer: A multicenter retrospective study

Lung Cancer. 2023 Sep:183:107315. doi: 10.1016/j.lungcan.2023.107315. Epub 2023 Jul 24.

Authors

Jiayan Chen¹, Chunwei Xu², Qian Wang³, Jiawen Lv⁴, Wanjun Lu⁴, Yixue Zhang⁴, Yanwen Yao⁴, Xiaoling Gu⁴, Guannan Wu⁴, Yue Hao⁵, Weiwei Pan⁶, Wenxian Wang⁷, Shirong Zhang⁸, Tangfeng Lv⁹, Yong Song¹⁰, Dong Wang¹¹

Affiliations

¹ Department of Respiratory Medicine, Affiliated Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu 210002, China.
² Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
³ Department of Respiratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu 210029, China.
⁴ Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China.
⁵ Department of Clinical Trial, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, China.
⁶ Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing, Zhejiang 314001, China.
⁷ Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, China.
⁸ Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.
⁹ Department of Respiratory Medicine, Affiliated Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu 210002, China; Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China.
¹⁰ Department of Respiratory Medicine, Affiliated Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu 210002, China; Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China. Electronic address: yong.song@nju.edu.cn.
¹¹ Department of Respiratory Medicine, Affiliated Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu 210002, China; Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China. Electronic address: doyle_wd@126.com.

PMID: 37517117
DOI: 10.1016/j.lungcan.2023.107315

Abstract

Background: Although the treatment of ERBB2-altered non-small cell lung cancer (NSCLC) has been studied for many years, there are no comprehensive studies to evaluate the benefits of various therapies as first-line treatment. Through the development of immunotherapy, more and more different combination treatments were applicated in clinical practice, therefore, we conducted a multicenter retrospective study to evaluate the efficacy of different treatments.

Methods: We enrolled patients with ERBB2-altered NSCLC who had undergone at least one-line systemic anticancer treatment to evaluate the efficacy of first-line chemotherapy alone (Chemo), anti-ERBB2 tyrosine kinase inhibitor (TKI), chemotherapy plus immunotherapy (Chemo + Immuno), chemotherapy plus anti-angiogenesis therapy (Chemo + Antiangio) and chemotherapy combined with immunotherapy and anti-angiogenesis therapy (Chemo + Immuno + Antiangio). The clinical outcomes included objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), one-year and three-year survival rate.

Results: We enroll 36 patients harboring ERBB2 mutation and 29 with ERBB2 amplification. The overall ORR was 30.8%, DCR was 69.2% and mPFS was 5.7 months. Chemo + Immuno and Chemo + Antiangio both achieved longer mPFS than TKI (7.8 vs 3.6 months, HR: 0.24, 95 %CI: 0.09-0.64, P = 0.002; 5.9 vs 3.6 months, HR: 0.36, 95 %CI: 0.15-0.88, P = 0.019; respectively), while there was no significant difference in mPFS between Chemo + Immuno or Chemo + Antiangio and Chemo (both P > 0.05), the mPFS of the first two was longer. For ERBB2-mutant patients, the mPFS was 5.9 months, and Chemo + Immuno and Chemo + Antiangio both achieved longer mPFS than TKI (12.9 vs 2.9 months, HR: 0.15, 95 %CI: 0.03-0.68, P = 0.005; 7.1 vs 2.9 months, HR: 0.50, 95 %CI: 0.29-0.88, P = 0.009, respectively). In the same therapies, patients with ERBB2 mutation or ERBB2 amplification showed no statistical significance in PFS (both P > 0.05).

Conclusions: In the first-line treatment of ERBB2-altered NSCLC, chemotherapy combined with immunotherapy or anti-angiogenesis therapy may have greater survival benefits than ERBB2-target therapy, but the efficacy may not be better than that of chemotherapy.

Keywords: ERBB2 alteration; Non-small-cell lung cancer (NSCLC); Real-world study; Treatment.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Mutation
Protein Kinase Inhibitors / adverse effects
Retrospective Studies

Substances

Protein Kinase Inhibitors