HER2 mutated metastatic non-small cell lung cancer | Primary Research (KOL's Insight) | Market Intelligence | Epidemiology & Market Forecast-2035

Gene mutations, gene amplifications, and protein overexpression are among the NSCLC alterations that activate HER2. In particular, the HER2 exon 20 mutation has received strong clinical validation as a biomarker. For NSCLC patients with HER2 mutations, there are currently few approved targeted therapies. Few studies on HER2 mutations in NSCLC have been published to date, mostly in Asian patient populations where never smokers make up a larger proportion of lung cancer patients (roughly 30%) than in North American and European populations (10%). According to reports, HER2 mutations have been discovered in 2-5% of NSCLC adenocarcinomas. In non-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) alterations, chemotherapy remains the standard treatment over a decade, due to the minor efficacy of traditional pan-HER tyrosine kinase inhibitors (TKIs) and HER2-targeted monoclonal antibodies.

Description

An increasingly popular therapeutic target for non-small cell lung cancer (NSCLC) is the human epidermal growth factor receptor 2 (HER2), a member of the ERBB family of tyrosine kinase receptors. Gene mutations, gene amplifications, and protein overexpression are among the NSCLC alterations that activate HER2. In particular, the HER2 exon 20 mutation has received strong clinical validation as a biomarker. For NSCLC patients with HER2 mutations, there are currently few approved targeted therapies. The way non-small cell lung cancer patients are treated has changed recently as a result of advances in our understanding of oncogenic driver changes and the development of targeted therapies. Today, a thorough molecular analysis is always included in the treatment of NSCLC. Novel treatment approaches are necessary because not all oncogenic driver changes have efficient targeted therapeutics. Within the EGFR (epidermal growth factor receptor) family of tyrosine kinase receptors, the human epidermal growth factor receptor 2/Erb-B2 receptor tyrosine kinase 2 (HER2/ERBB2) is a recently discovered therapeutic target. The PI3K/AKT and MEK/ERK pathways are phosphorylated and activated as a result of dimerization with other ligand-bound HER family members because HER2 lacks a recognized soluble ligand. Increased dimerization and autophosphorylation caused by modifications in the HER2 pathway promote oncogenesis and unchecked cell proliferation.

HER2 mutated metastatic non-small cell lung cancer (Epidemiology)

Few studies on HER2 mutations in NSCLC have been published to date, mostly in Asian patient populations where never smokers make up a larger proportion of lung cancer patients (roughly 30%) than in North American and European populations (10%). According to reports, HER2 mutations have been discovered in 2-5% of NSCLC adenocarcinomas. Retrospective analysis of pulmonary resection samples obtained at the Fudan University Shanghai Cancer Center included 202 patients with lung adenocarcinoma who had not undergone neoadjuvant chemotherapy and had never smoked. The median age at diagnosis was 57.3 years, and there were no discernible differences between males and females in terms of age, stage, or degree of tumor differentiation. In these samples, 89.1% had known oncogenic driver mutations in the EGFR (75.25%), HER2 (5.94%), ALK fusion (4.95%), KRAS (1.98%), and ROS1 fusion (0.99%) genes. Patients who did not have a known driver mutation were diagnosed when they were younger. It was discovered that 12 samples had HER2 kinase domain mutations, including 11 exon 20 insertions and 1 L775P point mutation.

HER2 mutated metastatic non-small cell lung cancer -Current Market Size & Forecast Trends

The market for HER2 mutated metastatic non-small cell lung cancer (NSCLC) is projected to grow significantly, with a total market size estimated at around USD 120 million in 2022 across the major markets and expected to expand as new therapies are developed and approved. The increasing focus on targeted therapies, particularly oral tyrosine kinase inhibitors like BAY 2927088 and zongertinib, is driving this growth, as these treatments have shown promising efficacy in clinical trials, including a reported overall response rate of 72.1% for BAY 2927088. The overall NSCLC market is anticipated to register a CAGR of 9.5% from 2025 to 2030, bolstered by rising incidences of lung cancer and ongoing research efforts. North America is expected to capture a significant share of this market due to its advanced healthcare infrastructure and the presence of key industry players. As research progresses and more targeted therapies receive regulatory approval, the market for HER2 mutated metastatic NSCLC is well-positioned for substantial growth through 2035.

In non-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) alterations, chemotherapy remains the standard treatment over a decade, due to the minor efficacy of traditional pan-HER tyrosine kinase inhibitors (TKIs) and HER2-targeted monoclonal antibodies. In recent years, novel selective HER2 TKIs have been developed for pretreated HER2-mutant patients. In particular, pyrotinib has shown moderate efficacy as well as a manageable safety profile, and it is now being further evaluated as monotherapy or combined with other existing therapies; by contrast, while poziotinib has demonstrated promising preliminary results, the high rates of toxicity has hampered subsequent studies. Most notably, trastuzumab deruxtecan (T-DXd, DS-8201) has led to a significant breakthrough, with the most encouraging efficacy data (response rate of 55 %, median progression-free survival of 8.2 months and median overall survival of 17.8 months) among all the anti-HER2 agents. This is certainly remarkable progress, and T-DXd is undoubtedly the key drug for the treatment of this disease. Future developments regarding T-DXd are favourable, including shifting from monotherapy to combination strategies, improving structural design to optimise antitumor activity and minimize toxicity, identifying the potential resistance mechanisms and developing therapeutic strategies to overcome them.

Report Highlights

HER2 mutated metastatic non-small cell lung cancer - Current Market Trends

HER2 mutated metastatic non-small cell lung cancer - Current & Forecasted Cases across the G8 Countries

HER2 mutated metastatic non-small cell lung cancer - Market Opportunities and Sales Potential for Agents

HER2 mutated metastatic non-small cell lung cancer - Patient-based Market Forecast to 2035

HER2 mutated metastatic non-small cell lung cancer - Untapped Business Opportunities

HER2 mutated metastatic non-small cell lung cancer - Product Positioning Vis-a-vis Competitors' Products

HER2 mutated metastatic non-small cell lung cancer - KOLs Insight