Abstract
BackgroundHER2 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.MethodsAdvanced 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.ResultsBetween 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).ConclusionsHER2 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 pointsChemotherapy achieved better outcomes than afatinib for Chinese HER2 mutated advanced NSCLC patients, especially for the most common subtype, YVMA insertions.
Highlights
Human epidermal growth factor receptor2 (HER2) mutation is found in 1-2% of lung cancer patients
tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptors (EGFR), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) and B-Raf protooncogene serine/threonine kinase (BRAF) have been developed and put into practice[2,3,4,5], while those who do not harbor these mutations have a choice between traditional chemotherapy and immunotherapy as standard of care
We found HER2 mutated lung cancer patients had dilemmas when choosing their treatment plans: they do harbor driver mutations but cannot take targeted drugs approved by food and drug administration; their counterparts in breast cancer can benefit from HER2 mono-antibodies like trastuzumab while they themselves cannot[7]; guideline-directed suggestions to their treatment were barely written
Summary
Chemotherapy remains the standard of care for patients harboring HER2 mutations, while many HER2 targeted tyrosine kinase inhibitors (TKIs) have been applied to them in practice in recent years. This study was aimed to investigate the molecular and clinical patterns of HER2 mutations in advanced non-small cell lung cancer, and compare the different outcomes between chemotherapy and HER2-TKIs. Say cancer is the emperor of all maladies, lung cancer may be the king of all cancers, with the highest mortality rate and a rather high incidence in both sex. A minority in lung cancer patients are drawing more attention, who have driver mutations other than the forgoing ones, such as RET, HER2 and so on. These patients pitifully cannot benefit from targeted therapies and still struggling with side effects of chemo agents
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
