The Effects of HER2 Alterations in EGFR Mutant Non-small Cell Lung Cancer

Abstract

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High Expression of NT5DC2 Is a Negative Prognostic Marker in Pulmonary Adenocarcinoma

“…While SCLC is known for its high mutational load [3] and devastating prognosis, NSCLC includes targetable oncogenic driver mutations [4], such as Kirsten rat sarcoma (KRAS) [5], epidermal growth factor receptor (EGFR) [6,7], anaplastic lymphoma kinase (ALK) [8], Serine/threonine-protein kinase B-rapidly accelerated fibrosarcoma (BRAF) [9,10], rearranged during transfection (RET) [11], Proto-oncogene tyrosineprotein kinase ROS (ROS1) [12] and rarely neurotrophic tropomyosin receptor kinases (NTRK) [13]. Moreover, latest research has focused on co-mutations of multiple oncogenic and/ or tumor-suppressing pathways in NSCLC, as individual treatment approaches and prognostic implications might heavily differ [14][15][16]. While targeting oncogenic drivers is promising, addressing tumor suppressors in general is challenging and the clinical and therapeutical implications of co-mutations have not fully been understood [14].…”

Epidermal growth factor receptor compound and concomitant mutations: advances in precision treatment strategies

“…In addition, a retrospective study found that patients with concurrent EGFR mutations and HER2 amplification had better survival over patients with only EGFR mutations who received EGFR-TKIs (median OS: 846.0 days vs . 286.0 days, HR: 2.28, 95% CI: 1.29–4.05, P < 0.01) [68] …”

“…In addition, a retrospective study found that patients with concurrent EGFR mutations and HER2 amplification had better survival over patients with only EGFR mutations who received EGFR-TKIs (median OS: 846.0 days vs. 286.0 days, HR: 2.28, 95% CI: 1.29-4.05, P < 0.01). [68] Thus, although EGFR-TKI monotherapy showed more survival benefits than chemotherapy for patients with concomitant mutations, in most cases, the prognosis was poorer than that of those without concomitant mutations, and the specific survival benefit should thus be based on the type of concomitant mutations. Considering the inconsistent results for several concomitant mutation studies, further explorations with larger sample sizes are needed.…”

“…Median OS: 846.0 days [67] Combination therapies with different TKIs MET inhibitor tivantinib plus erlotinib EGFR-mutant patients without previously EGFR or MET inhibitor ORR: 60.7%; median PFS: 13.0 months [68] EGFR-TKI plus crizotinib Concomitant MET-amplification ORR: 48.6%; median PFS: 5.0 months; median OS: 10.0 months [69] Osimertinib and savolitinib…”

HER2-Altered Non-Small Cell Lung Cancer: Biology, Clinicopathologic Features, and Emerging Therapies

“…Concomitant HER2 alterations were proved to have an impact on the efficacy of targeted therapies. A retrospective study demonstrated that patients with concurrent EGFR mutation and HER2 amplification had a longer median time on treatment with EGFR-TKIs than those with EGFR mutation without HER2 amplification (846 days vs. 286 days, P =0.004) ( 37 ). However, in the post-hoc subgroup study of HER-CS, HER2 expression in EGFR-mutant patients may negatively impact the time-to-treatment failure (TTF) of EGFR-TKIs in the subgroup with a performance status (PS) of 2 ( 38 ).…”