types including pancreatic adenocarcinoma, colorectal, salivary gland, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma responded to selpercatinib, emphasizing the importance of basket clinical trial designs in driving progress in precision medicine. Delivering a Cytotoxic Drug Precisely to Ovarian Cancer Cells In 2023, an estimated 19,710 new cases of ovarian cancer will be diagnosed in the United States, and 13,270 women will die from the disease (28). Many patients with ovarian cancer are diagnosed at an advanced stage. Patients with advanced disease are usually treated with platinum-based chemotherapeutics. Although most patients respond initially to platinum-based treatment, nearly 80 percent will experience relapse. Unfortunately, patients with recurrent ovarian cancer are resistant to platinum-based treatments and have a poor prognosis. Folate receptor alpha (FRα) is a cell surface protein that binds to and transports folate (also known as vitamin B9) into cells. Research has shown that FRα is expressed at much higher levels in advanced ovarian cancer cells, compared to healthy adult tissues (396). There is also emerging evidence, including clinical data, that elevated FRα expression may be associated with lack of response to standard chemotherapy in ovarian cancer (397). These attributes make FRα a promising target for therapeutic intervention in ovarian cancer. The molecularly targeted therapeutic mirvetuximab soravtansine-gynx (Elahere) targets FRα and, in November 2022, received FDA approval for adult patients with FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. FDA also approved the companion diagnostic VENTANA FOLR1 RxDx Assay to identify patients eligible for the therapy. Mirvetuximab soravtansine-gynx is an antibody–drug conjugate designed to deliver a cytotoxic drug to cells that express FRα. It is the first antibody–drug conjugate to be approved by FDA to treat platinum-resistant ovarian cancer and marks the first FDA approval since 2014 for platinum chemotherapy-resistant ovarian cancer, which is associated with a poor prognosis. The approval was based on results from a phase III clinical trial that enrolled 106 patients. Nearly 32 percent of patients responded to mirvetuximab soravtansinegynx, with a median duration of response of 6.9 months (396,397). The approval of mirvetuximab soravtansine-gynx is great news for patients, such as Jaclyn (Jackie) Vanraaphorst, p. 88. There is preliminary evidence that mirvetuximab soravtansine-gynx also improves overall survival for this FRαpositive ovarian cancer patient population (398). A common adverse effect of mirvetuximab soravtansine-gynx is ocular toxicity—changes that affect the structure or function of the eye. Therefore, FDA approved mirvetuximab soravtansinegynx with a warning that patients being treated with the molecularly targeted therapeutic be monitored and treated for signs and symptoms of vision impairment and corneal disorders. Improving Outcomes for Patients with Metastatic Breast Cancer Despite major advances in the treatment of breast cancer, it remains the second leading cause of cancer-related death for women in the United States (28). Recent FDA decisions have the potential to power more progress against breast cancer because they have provided new therapeutic options for certain patients with the disease. For patients with breast cancer, one factor determining what treatment options should be considered is the presence or absence of three tumor biomarkers, estrogen and progesterone hormone receptors, which drive tumor growth upon engagement with their respective hormones, and the protein HER2. About 70 percent of breast cancers diagnosed in the United States are characterized as hormone receptor–positive and HER2-negative (3). Potential treatment options for these patients include the combination of an antihormone therapeutic such as tamoxifen, which works by preventing the hormone estrogen from attaching to its receptor; or letrozole, which works by lowering the level of estrogen in the body; or fulvestrant, which works by destroying estrogen receptors (ER) with a cyclin-dependent kinase 4/6 inhibitor. Treatment with antihormone therapeutics is also called endocrine therapy. Unfortunately, most advanced, hormone receptor-positive breast cancers that initially respond to endocrine therapy eventually become treatment resistant (see Sidebar 35, p. 87). In November 2021, FDA approved pafolacianine (Cytalux), the first tumor imaging agent for ovarian cancer that works by binding to the folate receptor, to assist surgeons in visualizing hard to detect lesions in adult patients during the surgery (1). pafolacianine (Cytalux) cancer cell folate receptor AACR Cancer Progress Report 2023 Advancing the Frontiers of Cancer Science and Medicine 86
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