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Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies

BACKGROUND: Lung cancer is now the leading cause of cancer mortality worldwide for both men and women. In non-small cell lung cancer (NSCLC), matching a specifically targeted drug to the identified driver mutation in each patient resulted in dramatically improved therapeutic efficacy, often in conju...

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Autores principales: Zhou, Jiebai, Ding, Ning, Xu, Xiaobo, Zhang, Yong, Ye, Maosong, Li, Chun, Hu, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325548/
https://www.ncbi.nlm.nih.gov/pubmed/32647540
http://dx.doi.org/10.1177/1758835920936090
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author Zhou, Jiebai
Ding, Ning
Xu, Xiaobo
Zhang, Yong
Ye, Maosong
Li, Chun
Hu, Jie
author_facet Zhou, Jiebai
Ding, Ning
Xu, Xiaobo
Zhang, Yong
Ye, Maosong
Li, Chun
Hu, Jie
author_sort Zhou, Jiebai
collection PubMed
description BACKGROUND: Lung cancer is now the leading cause of cancer mortality worldwide for both men and women. In non-small cell lung cancer (NSCLC), matching a specifically targeted drug to the identified driver mutation in each patient resulted in dramatically improved therapeutic efficacy, often in conjunction with decreased toxicity. Mutations in HER2 have been identified as an oncogenic driver gene for NSCLC. This retrospective study was conducted to better understand the clinical outcomes of advanced lung cancer patients harboring HER2 mutations treated with chemotherapies and HER2-targeted agents, as well as the optimal clinical choice. METHODS: Patients who were diagnosed with advanced lung cancer (stage IIIB/IV) and had undergone molecular testing at Zhongshan Hospital, Fudan University, Shanghai, China from April 2016 to December 2018 were reviewed. For patients that had HER2 mutant advanced lung cancer, we analyzed their clinical and molecular features and clinical outcomes, including overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR). RESULTS: We identified 44 patients harboring HER2 mutations. Their median age was 56 years, with the majority being women (n = 24), never smokers (n = 32), and having the adenocarcinoma genotype (n = 42). Amongst the HER2 mutations present, a 12 base pair in-frame insertion in exon 20 with p.771insAYVM was the most common subtype in patients with known detail variants of HER2 mutation (9/27). The median OS from the date of advanced disease diagnosis was 9.9 months with 24 deaths, and a median follow-up of 12.7 months for survivors. For patients with a known HER2 exon 20 insertion mutation, OS tended to be superior (though not statistically) in the first-line HER2-TKI group to that in the group receiving chemotherapy (10.8 versus 9.8 months, p = 0.40). However, patients that received first-line chemotherapy had a median PFS of 5.9 months, numerically longer than that of the HER2-TKI group (4.6 months, p = 0.63). Patients who received HER2-targeted therapy as first-line therapy had an improved OS (10.8 versus 10.1 months, p = 0.30) and PFS (4.6 versus 2.8 months, p = 0.36) relative to those who received HER2-targeted therapy as subsequent-line therapy, although they did not meet the threshold for statistical significance. Furthermore, patients with AYVM mutation were associated with poor clinical outcomes. CONCLUSION: Pemetrexed-based chemotherapy remains an important component of care for patients with HER2-mutant NSCLC. HER2-TKI given as an initial therapy may bring more clinical benefits than when given as a subsequent-line therapy. Refining the patient population based on patterns of HER2 variants may help improve the efficacy of anti-HER2 treatment in lung cancer. Developing highly effective and tolerable HER2-targeted agents is urgently needed for this population.
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spelling pubmed-73255482020-07-08 Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies Zhou, Jiebai Ding, Ning Xu, Xiaobo Zhang, Yong Ye, Maosong Li, Chun Hu, Jie Ther Adv Med Oncol Original Research BACKGROUND: Lung cancer is now the leading cause of cancer mortality worldwide for both men and women. In non-small cell lung cancer (NSCLC), matching a specifically targeted drug to the identified driver mutation in each patient resulted in dramatically improved therapeutic efficacy, often in conjunction with decreased toxicity. Mutations in HER2 have been identified as an oncogenic driver gene for NSCLC. This retrospective study was conducted to better understand the clinical outcomes of advanced lung cancer patients harboring HER2 mutations treated with chemotherapies and HER2-targeted agents, as well as the optimal clinical choice. METHODS: Patients who were diagnosed with advanced lung cancer (stage IIIB/IV) and had undergone molecular testing at Zhongshan Hospital, Fudan University, Shanghai, China from April 2016 to December 2018 were reviewed. For patients that had HER2 mutant advanced lung cancer, we analyzed their clinical and molecular features and clinical outcomes, including overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR). RESULTS: We identified 44 patients harboring HER2 mutations. Their median age was 56 years, with the majority being women (n = 24), never smokers (n = 32), and having the adenocarcinoma genotype (n = 42). Amongst the HER2 mutations present, a 12 base pair in-frame insertion in exon 20 with p.771insAYVM was the most common subtype in patients with known detail variants of HER2 mutation (9/27). The median OS from the date of advanced disease diagnosis was 9.9 months with 24 deaths, and a median follow-up of 12.7 months for survivors. For patients with a known HER2 exon 20 insertion mutation, OS tended to be superior (though not statistically) in the first-line HER2-TKI group to that in the group receiving chemotherapy (10.8 versus 9.8 months, p = 0.40). However, patients that received first-line chemotherapy had a median PFS of 5.9 months, numerically longer than that of the HER2-TKI group (4.6 months, p = 0.63). Patients who received HER2-targeted therapy as first-line therapy had an improved OS (10.8 versus 10.1 months, p = 0.30) and PFS (4.6 versus 2.8 months, p = 0.36) relative to those who received HER2-targeted therapy as subsequent-line therapy, although they did not meet the threshold for statistical significance. Furthermore, patients with AYVM mutation were associated with poor clinical outcomes. CONCLUSION: Pemetrexed-based chemotherapy remains an important component of care for patients with HER2-mutant NSCLC. HER2-TKI given as an initial therapy may bring more clinical benefits than when given as a subsequent-line therapy. Refining the patient population based on patterns of HER2 variants may help improve the efficacy of anti-HER2 treatment in lung cancer. Developing highly effective and tolerable HER2-targeted agents is urgently needed for this population. SAGE Publications 2020-06-27 /pmc/articles/PMC7325548/ /pubmed/32647540 http://dx.doi.org/10.1177/1758835920936090 Text en © The Author(s), 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Zhou, Jiebai
Ding, Ning
Xu, Xiaobo
Zhang, Yong
Ye, Maosong
Li, Chun
Hu, Jie
Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies
title Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies
title_full Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies
title_fullStr Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies
title_full_unstemmed Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies
title_short Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies
title_sort clinical outcomes of patients with her2-mutant advanced lung cancer: chemotherapies versus her2-directed therapies
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325548/
https://www.ncbi.nlm.nih.gov/pubmed/32647540
http://dx.doi.org/10.1177/1758835920936090
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