Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP)

Dziadziuszko, Rafał; Smit, Egbert F.; Dafni, Urania; Wolf, Juergen; Wasąg, Bartosz; Biernat, Wojciech; Finn, Stephen; Kammler, Roswitha; Tsourti, Zoi; Rabaglio, Manuela; Ruepp, Barbara; Roschitzki-Voser, Heidi; Stahel, Rolf A.; Felip, Enriqueta; Peters, Solange

doi:10.1016/j.jtho.2019.02.017

Cited by 114 publications

(90 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among small molecule TKIs, afatinib was most widely used in China in recent years, with PFS ranging from 2.9 to 6 months. 20,[24][25][26][27] Poziotinib, neratinib and pyrotinib had similar PFS, with 4.5-5.5 months, 5.5 and 6.4 months, respectively. 9,28,29 Dacomitinib and Osimertinib had weaker effects on this population, either with a short PFS or being invalid in cell line experiments.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Treatment outcome and clinical characteristics of HER2 mutated advanced non‐small cell lung cancer patients in China

Gao

et al. 2020

Thoracic Cancer

View full text Add to dashboard Cite

Background HER2 mutation is found in 1%–2% of lung cancer patients. Studies comparing chemotherapy to HER2‐TKIs are limited. This study aimed to investigate the molecular and clinical patterns of HER2 mutations in advanced non‐small cell lung cancer (NSCLC), and compare the different outcomes between chemotherapy and HER2‐TKIs. Methods Advanced or recurrent non‐small cell lung cancer patients with de novo HER2 mutations (N = 75) were included in this study. Molecular information, clinical features, and treatment outcomes were retrospectively collected from a web‐based patient registry and hospital chart review. Results Between October 2012 and December 2018, 65 patients with in‐frame insertion mutations, eight with point mutations and two with gene amplification were found. The most common subtypes of insertion mutations were A775_G776insYVMA, G776delinsVC, and V777_G778insGSP. HER2 mutated patients were mostly young‐aged, females, never or light smokers, with adenocarcinoma. Chemotherapy achieved better outcomes than HER2‐TKIs (median PFS: 5.5 vs. 3.7 months in the first‐line setting and 4.2 vs. 2.0 months in the second‐line setting, P = 0.001 and 0.031, respectively). In particular for the most common subtype, YVMA insertions, PFS was significantly longer in chemotherapy than HER2‐TKIs both in the first‐line (6.0 vs. 2.6 months, P = 0.008) and the second‐line (4.2 vs. 2.6 months P < 0.001). Conclusions HER2 mutated lung cancer patients were younger, mostly females, never or light smokers, with histologically diagnosed adenocarcinomas. Compared with afatinib, chemotherapy might bring more benefit to HER2 mutated advanced lung cancer patients, especially the most common type of HER2 exon 20 insertions, A775_G776insYVMA subtype. Key points Chemotherapy achieved better outcomes than afatinib for Chinese HER2 mutated advanced NSCLC patients, especially for the most common subtype, YVMA insertions.

show abstract

Section: Discussionmentioning

confidence: 94%

“…This could mean that trastuzumab or T‐DM1 might be beneficial to a minority of patients. Among small molecule TKIs, afatinib was most widely used in China in recent years, with PFS ranging from 2.9 to 6 months . Poziotinib, neratinib and pyrotinib had similar PFS, with 4.5–5.5 months, 5.5 and 6.4 months, respectively .…”

Section: Discussionmentioning

confidence: 99%

Treatment outcome and clinical characteristics of HER2 mutated advanced non‐small cell lung cancer patients in China

Gao

et al. 2020

Thoracic Cancer

View full text Add to dashboard Cite

show abstract

“…Although the previous case report showed that ERBB2 mutated NSCLC patient could benefit from afatinib treatment, a retrospective study in China suggested that compared with chemotherapy, afatinib was not more beneficial to ERBB2 mutated NSCLC patients . Also, most of the clinical trials, including afatinib, dacomitinib, and neratinib, focused on ERBB2 exon 20 insertion mutations and failed with a low objective response rate of 11%–19% . Two‐phase II studies showed a promising response of poziotinib and pyrotinib in advanced NSCLC with ERBB2 exon 20 mutation.…”

Section: Discussionmentioning

confidence: 99%

Mutational landscape and characteristics of ERBB2 in non‐small cell lung cancer

et al. 2020

View full text Add to dashboard Cite

Background: Tyrosine kinase domain (TKD) mutation and particularly exon 20 insertion mutations of ERBB2 have been extensively reported in non-small cell lung cancer (NSCLC). Due to the increased accessibility of next-generation sequencing, more ERBB2 mutations within the non-TKD can be detected in clinical practice. Nevertheless, the clinical significance of non-TKD mutations remains unknown. Hence, this study was designed to comprehensively outline the landscape and characteristics of ERBB2 mutations in NSCLC. Methods: A total of 1934 patients with NSCLC from cBioPortal were included in the study. An ERBB2 mutation cohort was identified, while subsequent analyses revealed clinical and genomic characteristics. Results: The frequency of ERBB2 mutation was 4.5%, and it was determined to be more likely to occur in never-smokers. ERBB2 mutations occurring in the non-TKD accounted for 57.5% of ERBB2 mutations. In the non-TKD, missense mutation was the most recurrent mutation type, and S310F was the most recurrent mutation variant. ERBB2 mutations within non-TKD also had a strong oncogenic ability where up to 37.5% of ERBB2 oncogenic mutations were within non-TKD. The co-mutation of EGFR or KRAS was higher in the non-TKD mutation compared to the TKD mutation. Shorter overall survival was observed in ERBB2-mutant patients compared with ERBB2 wild-type patients. There was no significant difference in overall survival between patients with non-TKD mutations and TKD mutations. Conclusions: The present study showed that a considerable portion of non-TKD mutations were oncogenic. ERBB2 mutation was a poor prognostic factor. The non-TKD mutation might also be used as a therapeutic target in ERBB2-directed target therapy. Key points • Significant findings of the study ERBB2 mutations were more abundant within a nontyrosine domain than those within the tyrosine domain. Up to 37.5% of ERBB2 oncogenic mutations were within the nontyrosine domain. ERBB2 mutation was a poor prognostic factor.• What this study adds The frequency of EGFR or KRAS co-mutations were significantly higher in ERBB2 mutations within the nontyrosine kinase domain compared to ERBB2 mutations within the tyrosine kinase domain. Nontyrosine domain mutations confer equal overall survival to tyrosine domain mutations.

show abstract

“…82 The two phase II studies of afatinib in patients with exon 20 mutation reported disappointing results of disease control rate (DCR) at 71% including one out of seven uPRs, and a progression-free rate at 12-weeks of 54%, respectively. 83,84 In a multinational, retrospective study of afatinib, 3 out of 27 patients with HER-2 exon 20 mutations responded. Overall, two of the responders harboured YVA or VAG insertions and had received previous trastuzumab and pertuzumab.…”

Section: Her-2 Exon 20 Mutation and Amplificationmentioning

confidence: 99%

Targeting non-small cell lung cancer: driver mutation beyond epidermal growth factor mutation and anaplastic lymphoma kinase fusion

Chu

2020

Ther Adv Med Oncol

View full text Add to dashboard Cite

The identification of driver mutations in epidermal growth factor receptor, anaplastic lymphoma kinase, the BRAF and ROS1 genes and subsequent successful clinical development of kinase inhibitors not only significantly improves clinical outcomes but also facilitates the discovery of other novel driver mutations in non-small cell lung cancer. These driver mutations can be categorized into mutations in or near the kinase domain, gene amplification or fusion. In this review, BRAF V600E, EGFR and HER-2 exon 20 mutation, FGFR1–4, K-RAS, MET, neuregulin-1, NRTK, PI3K/AKT/mTOR, RET and ROS1 gene aberration and their therapeutics will be discussed.

show abstract

Afatinib in NSCLC With HER2 Mutations: Results of the Prospective, Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP)

Cited by 114 publications

References 32 publications

Treatment outcome and clinical characteristics of HER2 mutated advanced non‐small cell lung cancer patients in China

Treatment outcome and clinical characteristics of HER2 mutated advanced non‐small cell lung cancer patients in China

Mutational landscape and characteristics of ERBB2 in non‐small cell lung cancer

Targeting non-small cell lung cancer: driver mutation beyond epidermal growth factor mutation and anaplastic lymphoma kinase fusion

Contact Info

Product

Resources

About