Pivotal Presentations That May Shape the Breast Cancer Standard of Care

Anticipated updates in key breast cancer clinical trials at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting underscore “the importance of continued innovation in breast cancer therapy,” according to Reshma L. Mahtani, DO.

Ahead of the meeting, CancerNetwork® spoke with Mahtani, chief of breast medical oncology at Miami Cancer Institute of Baptist Health South Florida, about the presentations with the potential to shift the treatment paradigm across different types of breast cancer. Of note, Mahtani highlighted the phase 3 DESTINY-Breast09 trial (NCT04784715), which is assessing fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta); the phase 3 ASCENT-04/KEYNOTE-D19 study (NCT05382286), which is evaluating sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda); and the phase 3 VERITAC-2 trial (NCT05654623), which is investigating the novel proteolysis targeting chimera (PROTAC) vepdegestrant, as the developments to look out for at the meeting.

Transcript:

The first one would be the DESTINY-Breast09 trial. This is poised to be a pivotal presentation at ASCO this year. The study will potentially reshape the first-line treatment landscape for HER2-positive metastatic breast cancer. We heard interim results that T-DXd plus pertuzumab improved outcomes compared with standard treatment with a taxane, trastuzumab [Herceptin], and pertuzumab.1 But this study marks the first major advancement in first-line HER2-positive metastatic breast cancer treatment in over a decade, suggesting that antibody-drug conjugates like T-DXd could become foundational in earlier lines of therapy, so the standard of care is likely to change. [It is] so exciting for our patients.

The second study would be the ASCENT-04 trial, and this was a phase 3 study evaluating the combination of the TROP-2–directed [antibody-drug conjugate] sacituzumab govitecan in combination with the checkpoint inhibitor pembrolizumab as first-line treatment for metastatic triple-negative breast cancer [TNBC]. We heard in top-line results that this combination of [sacituzumab govitecan] plus pembrolizumab significantly improved progression-free survival compared with pembrolizumab and chemotherapy in patients with locally advanced, unresectable or metastatic TNBC as first-line therapy.2 Again, we’re focusing on the PD-L1–positive tumors as defined by a [combined positive score] of 10 or higher. Overall, I would say this trial provides hope for improved outcomes in a patient population with a high unmet medical need and underscores the importance of continued innovation in breast cancer therapy.

Finally, I would say the third abstract is the VERITAC-2 trial. We heard that this trial met its primary end point in the ESR1-mutated population, demonstrating a statistically significant improvement in progression-free survival with vepdegestrant, a potentially first-in-class investigational oral PROTAC estrogen receptor [ER] degrader, compared with fulvestrant.3 PROTACs are an exciting class of therapy because they don’t just block disease-causing proteins like the estrogen receptor; they degrade them entirely. This approach may overcome resistance seen with standard endocrine therapies and, importantly, can target proteins that traditional drugs can’t. For ER-positive breast cancer, this could mean more effective, longer-lasting treatment options, especially for patients with an ESR1 mutation.

References

1. Enhertu (fam-trastuzumab deruxtecan-nxki) plus pertuzumab demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival vs. THP as 1st-line therapy for patients with HER2-positive metastatic breast cancer. News release. AstraZeneca. April 21, 2025. Accessed May 29, 2025. https://tinyurl.com/ycxdtrvw
2. Trodelvy plus Keytruda demonstrates a statistically significant and clinically meaningful improvement in progression free survival in patients with previously untreated PD-L1+ metastatic triple-negative breast cancer. News release. Gilead Sciences Inc. April 21, 2025. Accessed May 29, 2025. https://tinyurl.com/3r97auu4
3. Arvinas and Pfizer announce positive topline results from phase 3 VERITAC-2 clinical trial. News release. Arvinas Inc. March 11, 2025. Accessed May 29, 2025. https://tinyurl.com/4cba6tj7