<![CDATA[Dr McCann on the FDA Approval of Vepdegestrant for ESR1-Mutated, ER+ Advanced Breast Cancer]]>

Advertisement Commentary|Videos|May 12, 2026 Dr McCann on the FDA Approval of Vepdegestrant for ESR1-Mutated, ER+ Advanced Breast Cancer Author(s)Kelly E. McCann, MD, PhD Fact checked by: Ashling Wahner , Riley Kandel Kelly Elizabeth McCann, MD, PhD, notes the role of vepdegestrant in the ESR1-mutated, ER-positive, HER2-negative advanced breast cancer treatment paradigm. Advertisement “Right now we have yet another oral SERD that is tied down to ESR1 mutations. The most important thing going forward is going to be combination therapy trials.”Kelly Elizabeth McCann, MD, PhD, an associate professor at the University of California San Diego, discussed the clinical significance of the FDA approval of vepdegestrant (Veppanu) for patients with ESR1-mutated, estrogen receptor (ER)–positive, HER2-negative advanced breast cancer.On May 1, 2026, the FDA approved vepdegestrant for the treatment of adult patients with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, who have experienced disease progression after receiving at least 1 line of endocrine therapy. McCann observed that although several oral selective ER degraders (SERDs) are currently under development, vepdegestrant uses a mechanism of action that differentiates it from other agents in its class.McCann detailed how vepdegestrant functions by bringing the ER into direct contact with an E3 ubiquitin ligase. This interaction facilitates the degradation of the receptor through the cellular ubiquitination and proteasome system, she said. A key pharmacological advantage of this agent highlighted by McCann is that the molecule is released after the degradation process is complete, allowing it to initiate subsequent cycles of receptor destruction. Currently, the regulatory path for vepdegestrant, much like other oral SERDs, is focused on patients with ESR1 mutations, she stated. These mutations represent a primary resistance mechanism that patients often develop following treatment with aromatase inhibitors, according to McCann.To address the need for more robust treatment options, McCann emphasized the importance of ongoing combination therapy trials. For example, she highlighted the phase 1b/2 ELEVATE trial (NCT05563220), which is evaluating the efficacy of elacestrant (Orserdu) in combination with other agents, such as ribociclib (Kisqali) and abemaciclib (Verzenio). Further clinical investigations are essential for generating the data necessary to guide real-world treatment decisions and to move the field toward more integrated therapeutic strategies, she emphasized. McCann concluded by noting that many of these treatment decisions will be driven by patient preference, with the hope of eventually replacing injectable therapies like fulvestrant (Faslodex) with effective oral options. NewsletterStay up to date on the most recent and practice-changing oncology dataSubscribe Now! Advertisement Related ContentAdvertisementDr Postow on an Ideal Post-ICI Monitoring Framework in Melanoma ByMichael A. Postow, MDMay 12th 2026Dr Postow on the Timing of Delayed or Re-Emergent irAEs in MelanomaByMichael A. Postow, MDMay 12th 2026Dr Parikh on the Feasibility and Importance of Immunotherapy Trials in Anal Cancer ByAparna R. 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