We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Immunotherapy as a later-line option for HER2-altered advanced non-small-cell lung cancer: taxane might be a favorable partner

    Yaning Yang‡

    Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Chaoyang District, Beijing, 100021, China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Guangjian Yang‡

    Department of Respiratory Medicine, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Weihua Li

    Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Chaoyang District, Beijing, 100021, China

    ,
    Haiyan Xu

    Department of Comprehensive Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Chaoyang District, Beijing, 100021, China

    ,
    Xuezhi Hao

    Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Chaoyang District, Beijing, 100021, China

    ,
    Shuyang Zhang

    Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Chaoyang District, Beijing, 100021, China

    ,
    Xin Ai

    Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Chaoyang District, Beijing, 100021, China

    ,
    Siyu Lei

    Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Chaoyang District, Beijing, 100021, China

    &
    Yan Wang

    *Author for correspondence: Tel.: +86 010 877 874 71;

    E-mail Address: wangyanyifu@163.com

    Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Chaoyang District, Beijing, 100021, China

    Published Online:https://doi.org/10.2217/fon-2022-0879

    Aim: To assess the effectiveness of different types of taxanes, including nab-paclitaxel, paclitaxel and docetaxel, and further compare the effectiveness of taxane-based chemotherapy, taxane-based chemotherapy plus angiogenesis inhibitors or taxane-based chemotherapy plus immune checkpoint inhibitors in HER2-altered non-small-cell lung cancer in the second- or third-line setting. Materials & methods: A total of 52 patients were included in the study. Progression-free survival was compared between subgroups. Results: A clinically meaningful improvement in progression-free survival was observed among patients in the nab-paclitaxel group compared with the docetaxel group. Taxane-based chemotherapy plus immune checkpoint inhibitors achieved longer progression-free survival than taxane-based chemotherapy. There was no difference between taxane-based chemotherapy plus immune checkpoint inhibitors and taxane-based chemotherapy plus angiogenesis inhibitors. Conclusion: Nab-paclitaxel appears to be a reasonable alternative to docetaxel. Chemotherapy plus immune checkpoint inhibitors might yield more survival benefits than chemotherapy alone.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J. Clin. 72(1), 7–33 (2022).
    • 2. Shigematsu H, Takahashi T, Nomura M et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res. 65(5), 1642–1646 (2005).
    • 3. Arcila ME, Chaft JE, Nafa K et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. Cancer Res. 18(18), 4910–4918 (2012). • Large-scale study demonstrating HER2 mutations in lung cancer.
    • 4. Mazières J, Peters S, Lepage B et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J. Clin. Oncol. 31(16), 1997–2003 (2013).
    • 5. Friedlaender A, Subbiah V, Russo A et al. EGFR and HER2 exon 20 insertions in solid tumours: from biology to treatment. Nat. Rev. Clin. Oncol. 19(1), 51–69 (2022). •• Review of HER2 exon 20 insertion and treatment perspectives.
    • 6. Auliac J-B, Dô P, Bayle S et al. Non-small cell lung cancer patients harboring HER2 mutations: clinical characteristics and management in a real-life setting. Cohort HER2 EXPLORE GFPC 02-14. Adv. Ther. 36(8), 2161–2166 (2019).
    • 7. Zhou J, Ding N, Xu X et al. Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies. Ther. Adv. Med. Oncol. 12, 1758835920936090 (2020).
    • 8. Eng J, Hsu M, Chaft JE, Kris MG, Arcila ME, Li BT. Outcomes of chemotherapies and HER2 directed therapies in advanced HER2-mutant lung cancers. Lung Cancer 99, 53–56 (2016).
    • 9. Mazières J. Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort. Ann. Oncol. 27(2), 6 (2016).
    • 10. Wang Y, Zhang S, Wu F et al. Outcomes of pemetrexed-based chemotherapies in HER2-mutant lung cancers. BMC Cancer 18(1), 326 (2018).
    • 11. Xu F, Yang G, Xu H, Yang L, Qiu W, Wang Y. Treatment outcome and clinical characteristics of HER2 mutated advanced non-small cell lung cancer patients in China. Thorac. Cancer 11(3), 679–685 (2020).
    • 12. Yang S, Wang Y, Zhao C et al. Exon 20 YVMA insertion is associated with high incidence of brain metastasis and inferior outcome of chemotherapy in advanced non-small cell lung cancer patients with HER2 kinase domain mutations. Transl. Lung Cancer Res. 10(2), 753–765 (2021).
    • 13. Lau SCM, Fares AF, Le LW et al. Subtypes of EGFR- and HER2-mutant metastatic NSCLC influence response to immune checkpoint inhibitors. Clin. Lung Cancer 22(4), 253–259 (2021).
    • 14. Lai W-CV, Feldman DL, Buonocore DJ et al. PD-L1 expression, tumor mutation burden and response to immune checkpoint blockade in patients with HER2-mutant lung cancers. J. Clin. Oncol. 36(Suppl. 15), 9060 (2018).
    • 15. Takeda M, Sakai K, Hayashi H et al. Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2. Oncotarget 9(30), 21132–21140 (2018).
    • 16. Mazieres J, Drilon A, Lusque A et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann. Oncol. 30(8), 1321–1328 (2019).
    • 17. Guisier F, Dubos-Arvis C, Viñas F et al. Efficacy and safety of anti-PD-1 immunotherapy in patients with advanced NSCLC with BRAF, HER2, or MET mutations or RET translocation: GFPC 01-2018. J. Thorac. Oncol. 15(4), 628–636 (2020).
    • 18. Chen K, Pan G, Cheng G et al. Immune microenvironment features and efficacy of PD-1/PD-L1 blockade in non-small cell lung cancer patients with EGFR or HER2 exon 20 insertions. Thorac. Cancer 12(2), 218–226 (2021).
    • 19. Cinausero M, Laprovitera N, De Maglio G et al. KRAS and ERBB-family genetic alterations affect response to PD-1 inhibitors in metastatic nonsquamous NSCLC. Ther. Adv. Med. Oncol. 11, 1758835919885540 (2019).
    • 20. Yang G, Yang Y, Liu R et al. First-line immunotherapy or angiogenesis inhibitor plus chemotherapy for HER2-altered NSCLC: a retrospective real-world POLISH study. Ther. Adv. Med. Oncol. 14, 17588359221082340 (2022). • Large population-based real-world study identifying the role of immune checkpoint inhibitors (ICIs) in first-line treatment.
    • 21. Saalfeld FC, Wenzel C, Christopoulos P et al. Efficacy of immune checkpoint inhibitors alone or in combination with chemotherapy in NSCLC harboring ERBB2 mutations. J. Thorac. Oncol. 16(11), 1952–1958 (2021). •• Evaluation of effectiveness of ICIs combined with chemotherapy.
    • 22. Zhu L, Chen L. Progress in research on paclitaxel and tumor immunotherapy. Cell. Mol. Biol. Lett. 24(1), 40 (2019).
    • 23. Paz-Ares L, Luft A, Vicente D et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N. Engl. J. Med. 379(21), 2040–2051 (2018).
    • 24. Schmid P, Adams S, Rugo HS et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 379(22), 2108–2121 (2018).
    • 25. Zhang G-C, Liao N, Chen B et al. Next-generation sequencing (NGS) identifies a new breast cancer subtype with HER2 low-amplification status as a candidate for targeted therapy. J. Clin. Oncol. 38(Suppl. 15), 553 (2020).
    • 26. Fang W, Zhao S, Liang Y et al. Mutation variants and co-mutations as genomic modifiers of response to afatinib in HER2-mutant lung adenocarcinoma. Oncologist 25(3), e545–e554 (2020).
    • 27. Bachelot T, Ciruelos E, Schneeweiss A et al. Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE). Ann. Oncol. 30(5), 766–773 (2019).
    • 28. Chen Y, Bao B, Lv Y et al. Nab-paclitaxel-based regimens with docetaxel-based regimens as neoadjuvant treatment for early breast cancer. Invest. New Drugs 39(2), 524–529 (2021).
    • 29. Yoneshima Y, Morita S, Ando M et al. Phase 3 trial comparing nanoparticle albumin-bound paclitaxel with docetaxel for previously treated advanced NSCLC. J. Thorac. Oncol. 16(9), 1523–1532 (2021).
    • 30. Socinski MA, Bondarenko I, Karaseva NA et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J. Clin. Oncol. 30(17), 2055–2062 (2012). • Randomized phase III trial evaluating the efficacy of nab-paclitaxel in non-small-cell lung cancer.
    • 31. Wu Y, Feng J, Hu W, Luo Q. A randomized placebo-controlled clinical study of nab-paclitaxel as second-line chemotherapy for patients with advanced non-small cell lung cancer in China. Biosci. Rep. 37(4), BSR20170020 (2017).
    • 32. Sakata S, Saeki S, Okamoto I et al. Phase II trial of weekly nab-paclitaxel for previously treated advanced non-small cell lung cancer: Kumamoto Thoracic Oncology Study Group (KTOSG) trial 1301. Lung Cancer 99, 41–45 (2016).
    • 33. Tanaka H, Taima K, Morimoto T et al. A single-arm phase II study of nab-paclitaxel for patients with chemorefractory non-small cell lung cancer. BMC Cancer 17(1), 683 (2017).