Antibody-drug conjugates (ADCs) have revolutionized the treatment landscape for breast cancer, offering targeted therapies that combine the specificity of monoclonal antibodies with the cytotoxic power of chemotherapy. Currently, there are four approved ADCs for the treatment of breast cancer: Kadcyla (trastuzumab emtansine), Enhertu (trastuzumab deruxtecan), Trodelvy (sacituzumab govitecan), and Ujvira (trastuzumab emtansine). Kadcyla made history in 2013 as the first ADC approved for breast cancer and the first ADC to gain approval for a solid tumor. It combines the HER2-targeting capabilities of trastuzumab with the cytotoxic agent emtansine (DM1). Kadcyla is indicated for patients with HER2-positive breast cancer who have previously received trastuzumab and a taxane, either in the neoadjuvant, adjuvant, or metastatic setting. This targeted approach has shown significant efficacy in improving survival rates and reducing the risk of disease recurrence.
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Following Kadcyla, Enhertu received approval in 2019 for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer. Specifically, it is indicated for those who have undergone two or more prior anti-HER2-based regimens in the metastatic setting or one such regimen in the neoadjuvant or adjuvant setting, provided there is evidence of disease recurrence within six months of completing therapy. Additionally, Enhertu has shown promise for patients with HER2-low metastatic breast cancer, broadening its applicability in the treatment landscape.
In 2020, Trodelvy was approved for previously treated metastatic breast cancer patients, specifically targeting those with hormone receptor-positive/HER2-negative (HR+/HER2-) subtypes and metastatic triple-negative breast cancer (TNBC). Trodelvy combines the targeting of the TROP-2 protein with the chemotherapeutic agent govitecan, demonstrating significant efficacy in challenging cancer types that often have limited treatment options.
Ujvira, approved in 2021, is notable as the first biosimilar of an ADC, representing a significant milestone in the field. It is utilized for the treatment of both early and advanced HER2-positive breast cancer, offering a more affordable option for patients and healthcare systems while maintaining the therapeutic benefits of the original Kadcyla.
Thus, the development of ADCs continues to be a vibrant area of research, with over 70 ADCs currently under investigation. One promising candidate is datopotamab deruxtecan, a collaboration between AstraZeneca and Daiichi Sankyo, which is currently under review for breast cancer treatment. Additionally, several other ADCs are in clinical trials, including 9MW2821, U3-1402, IKS014, ARX788, and AGX101.
In conclusion, the advent of ADCs represents a significant advancement in the targeted treatment of breast cancer, providing new hope for patients and clinicians alike in managing this complex disease. As research progresses, the landscape of breast cancer treatment continues to evolve, with ADCs playing a crucial role in improving patient outcomes.
