Development of treatment options for Chinese patients with advanced squamous cell lung cancer: focus on afatinib

Abstract

Lung cancer is the leading cause of cancer death in China, and approximately one third of these cancers are squamous cell carcinoma (SqCC) of the lung. Ethnic diversity and country-specific environmental factors can account for interindividual variations in response to and tolerability of anticancer therapies. Although several targeted therapies have recently been approved for patients with relapsed/refractory SqCC of the lung, only afatinib, an irreversible ErbB family blocker, has data of Chinese patients. In the Phase III LUX-Lung 8 trial, afatinib demonstrated a significant clinical benefit vs the reversible first-generation EGFR tyrosine kinase inhibitor erlotinib in both the overall population and the Chinese subset, with a manageable safety profile. Emerging biomarker data from LUX-Lung 8 suggest that patients with ErbB mutations, especially ErbB2, and those classified as "good" in the VeriStrat^® proteomic test, may benefit from afatinib treatment in particular, regardless of ethnicity, and may get a long-term response. In conclusion, afatinib is a valid second-line option for Chinese patients with SqCC of the lung, and specific biomarkers may help guide in treatment decision-making. Ongoing studies will provide further guidance on afatinib's place in the treatment algorithm, alongside the other novel targeted therapies.

Keywords: Chinese; EGFR; ErbB; NSCLC; afatinib; biomarker; squamous cell carcinoma.

Figure 1

Deaths caused by lung cancer in China and the USA from 1990 to 2016. Notes: Institute for Health Metrics and Evaluation (IHME). GBD Compare. Seattle, WA: IHME, University of Washington; 2017. Available from: http://vizhub.healthdata.org/gbd-compare. Accessed January 15, 2019.

Figure 2

Mechanism of action of (A) immune checkpoint inhibitors, (B) VEGFR inhibitors, and (C) EGFR/ErbB inhibitors. Abbreviations: MHC, major histocompatibility complex; PD-1, programmed cell death protein-1; PD-L1, programmed cell death ligand-1; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.

Figure 3

LUX-Lung 8: Kaplan–Meier plots for overall study population vs Chinese subgroup. (A) PFS (an independent review) and (B) OS for the overall treatment population; (A and B) Reprinted from Soria JC, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial, Lancet Oncol. 2015;16(8):897–907. Copyright © 2015, with permission from Elsevier. (C) PFS (an independent review) and (D) OS for the Chinese subgroup (C and D) Copyright ©2013. Dove Medical Press. Republished from Lu S, Li W, Zhou C, et al. Afatinib versus erlotinib for second-line treatment of Chinese patients with advanced squamous cell carcinoma of the lung: a subgroup analysis of the phase 3 LUX-Lung 8 trial. Onco Targets Ther. 2018;11:8565–8573. Abbreviations: OS, overall survival; PFS, progression-free survival.

Figure 4

LUX-Lung 8: frequency of ErbB family mutations in the overall TGA cohort and in patients who were LTRs to afatinib.*, Note: ^*There were three LTRs to erlotinib (one had a tumor with an EGFR mutation and two had tumors which were EGFR WT). Abbreviations: LTRs, long-term responders; TGA, tumor genetic analysis; WT, wild-type.

Figure 5

Comparison of (A) PFS and (B) OS between patients with the presence or the absence of ErbB family mutations. Note: Reproduced with permission from Goss GD, Felip E, Cobo M, et al. Association of ERBB mutations with clinical outcomes of afatinib- or erlotinib-treated patients with lung squamous cell carcinoma: secondary analysis of the LUX-Lung 8 randomized clinical trial. JAMA Oncol. 2018;4(9):1189–1197. Copyright©2018 American Medical Association. Abbreviations: OS, overall survival; PFS, progression-free survival.

Figure 6

LUX-Lung 8: relationship between VeriStrat classification, OS, and treatment group. (A) Kaplan–Meier curves of OS with afatinib vs erlotinib treatment and VS-G vs VS-P classification; (B) forest plot of OS by treatment group and VeriStrat classification; (C) relationship between VeriStrat classification and OS in all patients. Notes: ^aAdjusted for treatment effect. This Figure was published in Lung Cancer. 2017;109:101–108, Gadgeel S, Goss G, Soria JC, et al. Evaluation of the VeriStrat® serum protein test in patients with advanced squamous cell carcinoma of the lung treated with second-line afatinib or erlotinib in the phase III LUX-Lung 8 study. Copyright © 2017 Elsevier. Abbreviations: OS, overall survival; VS-G, VeriStrat-good; VS-P, VeriStrat-poor.

Figure 7

LUX-Lung 8: clinical outcomes, VeriStrat status, and biomarker frequency and biomarkers more commonly observed in LTRs than in the overall trial population. Abbreviations: CR, complete response; LTRs, long-term responders; n/a, not assessed; OS, overall survival; PR, partial response; SD, stable disease; VS-G, VeriStrat-good; VS-P, VeriStrat-poor.