R/R HER2+ metastatic colorectal cancer | Primary Research (KOL's Insight) | Market Intelligence | Epidemiology & Market Forecast-2035

HER2 is an established oncogenic driver in a wide range of tumor types. Despite these developments, the 5-year survival rates of patients with metastatic colorectal cancer (CRC) have not increased. The HER2 receptors, which protrude into cells, are a component of the biological pathway involved in cellular replication. Only 3-5% of people with metastatic colorectal cancer have somatic HER2 gene mutations or amplifications. HER2 was initially thought to be a biomarker of anti-EGFR therapy resistance, but in more recent years, it has shown promise as a potential therapeutic target. The most recent information relates to the HER2-directed antibody drug conjugate (ADC) Enhertu (trastuzumab deruxtecan), a precision cancer treatment that uses a linker attached to a monoclonal antibody that binds specifically to the HER2 protein to deliver cytotoxic chemotherapy to cancer cells.

Description

In colorectal cancer (CRC), HER2 overexpression has recently come to light as a tumor marker that may be susceptible to targeting. The HER2 receptors, which protrude inside cells, are part of the biological pathway involved in cellular replication. The HER2 receptor gene can occasionally develop mutations that can cause an excess of receptors to be produced. Cells multiply and spread as a result, free from the typical biological constraints. The term HER2-positive refers to cancer cells that overexpress the HER2 receptor. The HER2 oncogene is overexpressed in a small percentage of CRCs, and since this pathway has been successfully targeted in the treatment of other cancers like breast and gastric cancer, research is being done to ascertain whether it can also be used to treat CRC. Activation of the HER2 pathway as a bypass signaling pathway has been linked to resistance to anti-epidermal growth factor receptor antibody therapy in both the first-line and salvage settings. It has also been shown that metastatic CRC with RAS and BRAF wild type exhibits a higher incidence of HER2 amplification. The proto-oncogene Erb-B2 receptor tyrosine kinase 2 (HER2), which codes for a transmembrane glycoprotein receptor with tyrosine kinase activity and is located on chromosome 17q21, is also known as HER2. The only EGFR family member, HER2, does not bind ligands; however, homodimerization or heterodimerization with other EGFR family members (HER1/EGFR, HER3, HER4) causes transphosphorylation of the intracytoplasmic tyrosine kinase domain and activates a variety of downstream signal transduction pathways (e.g., JAK/STAT3, RAS/RAF/ERK, and PIK3K/AKT/mTOR. The HER2 oncogene's amplification or overexpression of its protein results in a hyperactivation of mitogenic signals, which promotes unrestrained cell proliferation and tumorigenesis even in the absence of ligands bound to other receptors. The HER2 gene, which is amplified in a fresh subset of mCRC patients, may be a novel oncotarget for this cancer.

R/R HER2+ metastatic colorectal cancer (Epidemiology)

Despite improvements in the management of metastatic colorectal cancer (CRC), patient survival rates at 5 years remain low. Somatic HER2 gene mutations and amplifications are present in only 3-5% of patients with metastatic colorectal cancer. HER2 was first considered as a biomarker for anti-EGFR therapy resistance, but in more recent years, its potential as a usable target has come into focus. Colon cancer incidence and mortality have been steadily declining in the United States over the past few decades, with incidence falling by an average of 2. mortality by two on average, and annual growth of four%. Between 2007 and 2016, the rate was 2% annually. is the third most common form of cancer in the nation and the third biggest killer of people who develop cancer, both men and women. Colon cancer in young adults is also becoming more prevalent. According to the American Cancer Society, 106,180 new cases of colon cancer will have been identified in Americans by 2022. Due to classification problems, 52,580 deaths are anticipated from colon cancer in 2022 (combining both types). Globally, 1,931,590 new cases of colon cancer will be discovered in 2020, making up 10% of all cancer cases. Location can influence the incidence up to six times.

R/R HER2+ metastatic colorectal cancer -Current Market Size & Forecast Trends

The market for relapsed or refractory (R/R) HER2-positive metastatic colorectal cancer (mCRC) is part of the broader colorectal cancer therapeutics market, which is projected to grow significantly. The overall colorectal cancer therapeutics market is expected to increase from approximately USD 22.36 billion in 2024 to around USD 75.39 billion by 2037, reflecting a compound annual growth rate (CAGR) of about 9.8%. Specifically, HER2 overexpression occurs in about 2-3% of colorectal cancer cases, and targeted therapies for this subset are gaining traction, particularly with ongoing clinical trials investigating anti-HER2 agents. As new treatments are developed and approved, including combinations with existing therapies, the market for R/R HER2-positive mCRC is anticipated to expand significantly through 2035, driven by advancements in precision medicine and increased focus on personalized treatment strategies.

The most recent data pertains to the HER2-directed antibody drug conjugate (ADC) Enhertu (trastuzumab deruxtecan), a precision cancer drug that uses a linker attached to a monoclonal antibody that binds specifically to the HER2 protein to deliver cytotoxic chemotherapy to cancer cells. Enhertu's (trastuzumab deruxtecan) significant toxicity, however, led to an excess of mortality when it was active. There are many different types of targeted cancer therapies that bind to different sites along the HER2 pathway to stop the growth and division of cancer cells. Two specifically designed anticancer drugs, Tykerb (lapatinib) and Herceptin (trastuzumab), bind to the HER pathway in different ways. When tested on advanced HER2 wild type KRAS patients with advanced colon cancer, the combination is efficient and well tolerated. Tykerb and Herceptin might not be as efficient as other HER2-targeting, precision cancer drugs currently in development. Tukysa (tucatinib), a tyrosine kinase inhibitor, has a negligible impact on EGFR while having a high selectivity for the HER2 protein. Significant adverse side effects are associated with EGFR inhibition, including diarrhea and skin rash. HER2 advanced colorectal cancer patients with HER2 RAS wild-type metastatic colorectal cancer who had received first- and second-line standard-of-care therapies were enrolled in the single arm phase 2 clinical trial known as MOUNTAINEER to evaluate the efficacy of combination HER2 therapy with Herceptin and Tukysa. Patients with metastatic CRC who had RAS wild-type and HER2 amplification responded positively to the combination of Herceptin and Perjeta in the TRIUMPH clinical trial. There was a 35% response rate among 19 patients with metastatic CRC who were unresponsive to conventional chemotherapy and had tumors that were RAS wild-type and HER2-amplified overall. The combination has been shown to have cardiac and infusion-related side effects.

Report Highlights

R/R HER2+ metastatic colorectal cancer - Current Market Trends

R/R HER2+ metastatic colorectal cancer - Current & Forecasted Cases across the G8 Countries

R/R HER2+ metastatic colorectal cancer - Market Opportunities and Sales Potential for Agents

R/R HER2+ metastatic colorectal cancer - Patient-based Market Forecast to 2035

R/R HER2+ metastatic colorectal cancer - Untapped Business Opportunities

R/R HER2+ metastatic colorectal cancer - Product Positioning Vis-a-vis Competitors' Products

R/R HER2+ metastatic colorectal cancer - KOLs Insight