Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

ERS Congress 2024

Keep up to date on the latest news from the annual European Respiratory Society conference.
ADVANCED SEARCH
Log in
Top
Experimental Hematology & Oncology
Published in:

Open Access 01-12-2023 | NSCLC | Research

Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials

Authors: Shiqi Mao, Shuo Yang, Xinyu Liu, Xingya Li, Qiming Wang, Yiping Zhang, Jianhua Chen, Yan Wang, Guanghui Gao, Fengying Wu, Tao Jiang, Jiao Zhang, Ying Yang, Xiang Lin, Xiaoyu Zhu, Caicun Zhou, Shengxiang Ren

Published in: Experimental Hematology & Oncology | Issue 1/2023

Login to get access

Abstract

Background

Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation.

Methods

Patients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated.

Results

This pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p < 0.001) than those with mutations. ctDNA of nonshedding and clearance exhibited significantly longer PFS (median: 10.2 vs. 9.8 vs. 5.6 months, p = 0.036) and a trend of longer OS (median: 35.3 vs. 18.1 vs. 14.6 months, p = 0.357) than those not.

Conclusion

Patients with TP53 wild type, ctDNA nonshedding, or clearance showed superior efficacy of pyrotinib in patients with HER2-mutated advanced NSCLC, which might be helpful to guide the utility of pyrotinib in clinical setting.
Trial registration: The patients were from two registered clinical trials (ClinicalTrials.gov: NCT02535507, NCT02834936).
Appendix
Available only for authorised users
Literature
1.
Oh DY, Bang YJ. HER2-targeted therapies—a role beyond breast cancer. Nat Rev Clin Oncol. 2020;17(1):33–48.CrossRefPubMed
2.
Chen R, Manochakian R, James L, Azzouqa AG, Shi H, Zhang Y, et al. Emerging therapeutic agents for advanced non-small cell lung cancer. J Hematol Oncol. 2020;13(1):58.CrossRefPubMedPubMedCentral
3.
Hotta K, Aoe K, Kozuki T, Ohashi K, Ninomiya K, Ichihara E, et al. A phase II study of trastuzumab emtansine in HER2-positive non-small cell lung cancer. J Thorac Oncol. 2018;13(2):273–9.CrossRefPubMed
4.
Li BT, Shen R, Buonocore D, Olah ZT, Ni A, Ginsberg MS, et al. Ado-Trastuzumab emtansine for patients with HER2-mutant lung cancers: results from a phase II basket trial. J Clin Oncol. 2018;36(24):2532–7.CrossRefPubMedPubMedCentral
5.
Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, et al. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med. 2022;386(3):241–51.CrossRefPubMed
6.
Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman JR, Bharat A, et al. Non-small cell lung cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2022;20(5):497–530.CrossRef
7.
Zhou C, Li X, Wang Q, Gao G, Zhang Y, Chen J, et al. Pyrotinib in HER2-mutant advanced lung adenocarcinoma after platinum-based chemotherapy: a multicenter, open-label, single-arm. Phase II Study J Clin Oncol. 2020;38(24):2753–61.CrossRefPubMed
8.
Wang Y, Jiang T, Qin Z, Jiang J, Wang Q, Yang S, et al. HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib. Ann Oncol. 2019;30(3):447–55.CrossRefPubMedPubMedCentral
9.
10.
Elamin YY, Robichaux JP, Carter BW, Altan M, Gibbons DL, Fossella FV, et al. Poziotinib for patients with HER2 exon 20 mutant non-small-cell lung cancer: results from a phase II trial. J Clin Oncol. 2022;40(7):702–9.CrossRefPubMed
11.
Liu SV, Villaruz LC, Lee VHF, Zhu VW, Baik CS, Sacher A, et al. LBA61 First analysis of RAIN-701: Study of tarloxotinib in patients with non-small cell lung cancer (NSCLC) EGFR Exon 20 insertion, HER2-activating mutations & other solid tumours with NRG1/ERBB gene fusions. Ann Oncol. 2020;31:S1189.CrossRef
12.
Ramalingam SS, Zhou C, Kim TM, Kim S-W, Yang JC-H, Riely GJ, et al. Mobocertinib (TAK-788) in EGFR exon 20 insertion (ex20ins)+ metastatic NSCLC (mNSCLC): Additional results from platinum-pretreated patients (pts) and EXCLAIM cohort of phase 1/2 study. J Clin Oncol. 2021;39((15_suppl)):9014.CrossRef
13.
Yang G, Xu H, Xu F, Yang L, Li H, Zhang S, et al. P86.02 pyrotinib combined with apatinib for HER2-mutant non-small cell lung cancer: interim analysis from a phase II clinical study. J Thorac Oncol. 2021;16(3):S672–3.
14.
Yang G, Xu H, Yang Y, Zhang S, Xu F, Hao X, et al. Pyrotinib combined with apatinib for targeting metastatic non-small cell lung cancer with HER2 alterations: a prospective, open-label, single-arm phase 2 study (PATHER2). BMC Med. 2022;20(1):277.CrossRefPubMedPubMedCentral
15.
Saalfeld FC, Wenzel C, Christopoulos P, Merkelbach-Bruse S, Reissig TM, Laßmann S, et al. Efficacy of immune checkpoint inhibitors alone or in combination with chemotherapy in NSCLC harboring ERBB2 mutations. J Thorac Oncol. 2021;16(11):1952–8.CrossRefPubMed
16.
17.
18.
19.
DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011;43(5):491–8.CrossRefPubMedPubMedCentral
20.
Lai Z, Markovets A, Ahdesmaki M, Chapman B, Hofmann O, McEwen R, et al. VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research. Nucleic Acids Res. 2016;44(11): e108.CrossRefPubMedPubMedCentral
21.
22.
Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38(16): e164.CrossRefPubMedPubMedCentral
23.
24.
25.
Rolfo C, Russo A. HER2 mutations in non-small cell lung cancer: a herculean effort to hit the target. Cancer Discov. 2020;10(5):643–5.CrossRefPubMed
26.
Zhao J, Xia Y. Targeting HER2 alterations in non-small-cell lung cancer: a comprehensive review. JCO Precis Oncol. 2020;4:411–25.CrossRefPubMed
27.
Mazières J, Barlesi F, Filleron T, Besse B, Monnet I, Beau-Faller M, et al. Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort. Ann Oncol. 2016;27(2):281–6.CrossRefPubMed
28.
Mazieres J, Drilon A, Lusque A, Mhanna L, Cortot AB, Mezquita L, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321–8.CrossRefPubMedPubMedCentral
29.
Negrao MV, Skoulidis F, Montesion M, Schulze K, Bara I, Shen V, et al. Oncogene-specific differences in tumor mutational burden, PD-L1 expression, and outcomes from immunotherapy in non-small cell lung cancer. J Immunother Cancer. 2021;9(8):e002891.CrossRefPubMedPubMedCentral
30.
31.
Majeed U, Manochakian R, Zhao Y, Lou Y. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol. 2021;14(1):108.CrossRefPubMedPubMedCentral
32.
Vokes NI, Chambers E, Nguyen T, Coolidge A, Lydon CA, Le X, et al. Concurrent TP53 mutations facilitate resistance evolution in EGFR-mutant lung adenocarcinoma. J Thorac Oncol. 2022;17(6):779–92.CrossRefPubMed
33.
Shi K, Wang G, Pei J, Zhang J, Wang J, Ouyang L, et al. Emerging strategies to overcome resistance to third-generation EGFR inhibitors. J Hematol Oncol. 2022;15(1):94.CrossRefPubMedPubMedCentral
34.
Yang Y, Huang J, Wang T, Zhou J, Zheng J, Feng J, et al. Decoding the evolutionary response to ensartinib in patients with alk-positive nsclc by dynamic circulating tumor DNA sequencing. J Thorac Oncol. 2021;16(5):827–39.CrossRefPubMed
35.
Zhang JT, Liu SY, Gao W, Liu SM, Yan HH, Ji L, et al. Longitudinal undetectable molecular residual disease defines potentially cured population in localized non-small cell lung cancer. Cancer Discov. 2022;12(7):1690–701.CrossRefPubMedPubMedCentral
36.
Jiang T, Jiang L, Dong X, Gu K, Pan Y, Shi Q, et al. Utilization of circulating cell-free DNA profiling to guide first-line chemotherapy in advanced lung squamous cell carcinoma. Theranostics. 2021;11(1):257–67.CrossRefPubMedPubMedCentral
37.
Ren S, Chen J, Xu X, Jiang T, Cheng Y, Chen G, et al. Camrelizumab plus carboplatin and paclitaxel as first-line treatment for advanced squamous NSCLC (CameL-Sq): a phase 3 TRIAL. J Thorac Oncol. 2022;17(4):544–57.CrossRefPubMed
38.
Goldberg SB, Narayan A, Kole AJ, Decker RH, Teysir J, Carriero NJ, et al. Early assessment of lung cancer immunotherapy response via circulating tumor DNA. Clin Cancer Res. 2018;24(8):1872–80.CrossRefPubMedPubMedCentral
Metadata
Title
Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials
Authors
Shiqi Mao
Shuo Yang
Xinyu Liu
Xingya Li
Qiming Wang
Yiping Zhang
Jianhua Chen
Yan Wang
Guanghui Gao
Fengying Wu
Tao Jiang
Jiao Zhang
Ying Yang
Xiang Lin
Xiaoyu Zhu
Caicun Zhou
Shengxiang Ren
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Experimental Hematology & Oncology / Issue 1/2023
Electronic ISSN: 2162-3619
DOI
https://doi.org/10.1186/s40164-023-00417-y

Other articles of this Issue 1/2023

Experimental Hematology & Oncology 1/2023 Go to the issue

Review

Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy

Review

Ubiquitin-specific protease 28: the decipherment of its dual roles in cancer development

Review

Targeting CD22 for B-cell hematologic malignancies

Review

EZH2 in hepatocellular carcinoma: progression, immunity, and potential targeting therapies

Research

p53 directly downregulates the expression of CDC20 to exert anti-tumor activity in mantle cell lymphoma

Correspondence

Preclinical activity of selinexor in combination with eribulin in uterine leiomyosarcoma