OncLive Polls Spotlight Phase 3 Breast Cancer Studies Generating Buzz Ahead of ASCO 2025

2025 ASCO Annual Meeting Breast Cancer Abstracts

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As the 2025 ASCO Annual Meeting quickly approaches, several phase 3 breast cancer studies have emerged as major points of interest among oncology professionals. To assess which datasets are generating the most anticipation, OncLive® conducted informal polls on social media, querying breast cancer specialists on X and LinkedIn about the late-breaking abstracts they are most eager to see presented during the meeting.

Among 28 respondents on X, the phase 3 DESTINY-Breast09 (NCT04784715) and SERENA-6 (NCT04964934) trials garnered the greatest attention, with 46.4% and 39.3% of votes, respectively. The phase 3 VERITAC-2 (NCT05654623) and ASCENT-04 (NCT05382286) trials were also of interest, each cited by 7.1% of respondents.

X Breast Cancer Trials Poll

On LinkedIn, DESTINY-Breast09 remained the top-ranked abstract among over half (57%) of 58 respondents. However, ASCENT-04 was identified as the second most anticipated abstract in this poll (24%), followed by SERENA-6 (14%) and VERITAC-2 (5%).

LinkedIn Breast Cancer Trials Poll

Oncologists were also asked to identify the breast cancer subtypes they were most interested in ahead of ASCO. Among 59 X respondents, HER2-positive breast cancer led (39%), followed by triple-negative breast cancer (TNBC; 32.2%), hormone receptor (HR)–positive disease (20.3%), and early-stage disease (8.5%).

X Breast Cancer Subtypes Poll

In contrast, among 84 LinkedIn respondents, TNBC was the most selected subtype (50%), followed by HER2-positive (24%), HR-positive (20%), and early-stage disease (6%).

LinkedIn Breast Cancer Subtypes Poll

Based on these poll results, OncLive has assembled a ranked overview of the most highly anticipated abstracts, including key details on trial design, previously reported findings, and relevant regulatory updates. Read on for a closer look at each study.

LBA1008: Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): interim results from DESTINY-Breast09.

Session time: Tuesday June 2nd, 7:30-8:00am CDT

The DESTINY-Breast09 trial is a global, randomized, open-label study evaluating the efficacy and safety of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) with or without pertuzumab (Perjeta) vs the current first-line standard of care (SOC)—a taxane plus trastuzumab and pertuzumab (THP)—in patients with HER2-positive metastatic breast cancer.1

The trial enrolled approximately 1157 patients who had not received prior chemotherapy or HER2-targeted therapy for advanced or metastatic disease. Patient were randomly assigned 1:1:1 to 3 arms: T-DXd monotherapy, T-DXd combined with pertuzumab, or the THP regimen. The primary end point is progression-free survival (PFS) assessed by blinded independent central review (BICR), with secondary end points including overall survival (OS), objective response rate (ORR), duration of response (DOR), safety, and quality of life measures.

Results from a planned interim analysis of DESTINY-Breast09 indicated that the combination of T-DXd and pertuzumab demonstrated a statistically significant and clinically meaningful improvement in PFS compared with the THP regimen in a broad population of patients with HER2-positive breast cancer, suggesting potential superiority over the historical SOC.2 Notably, this PFS benefit was observed across all patient subgroups. Full data from this analysis will be presented at the meeting.

LBA4: Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): phase 3, double-blind ctDNA-guided SERENA-6 trial.

Session time: Monday June 1st, 1:00-4:00pm CDT

The ongoing SERENA-6 trial is a global, double-blind, randomized study evaluating the efficacy and safety of camizestrant, a next-generation oral selective estrogen receptor degrader, in combination with a CDK4/6 inhibitor (palbociclib [Ibrance], ribociclib [Kisqali], or abemaciclib [Verzenio]) vs continuation of an aromatase inhibitor (AI) plus a CDK4/6 inhibitor in patients with HR-positive, HER2-negative advanced breast cancer with an emergent ESR1 mutation.3 The trial employs a circulating tumor DNA–guided approach to detect ESR1 mutations before clinical disease progression, allowing for an early switch in endocrine therapy.

A total of 315 patients were randomly assigned 1:1 to either continue on an AI plus CDK4/6 inhibition or switch to camizestrant plus CDK4/6 inhibition upon detection of ESR1 mutations without disease progression.3,4 The primary end point is PFS, with secondary end points including time to second disease progression, OS, chemotherapy-free survival, safety, and patient-reported outcomes (PROs).

Interim results from the SERENA-6 trial demonstrated that switching to camizestrant plus a CDK4/6 inhibitor significantly improved PFS compared to continuing an AI plus CDK4/6 inhibitor therapy in patients with ESR1 mutations.4 The combination was well tolerated, with a safety profile consistent with known effects of the individual agents. These findings suggest that early intervention with camizestrant upon detection of ESR1 mutations may delay disease progression and extend the benefit of first-line treatment.

These data will be presented at ASCO and shared with global regulatory authorities.

LBA109: Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study.

Session time: Sunday May 31st, 1:15-4:15pm CDT

The ASCENT-04/KEYNOTE-D19 trial is evaluating the efficacy and safety of combining sacituzumab govitecan-hziy (Trodelvy) with pembrolizumab (Keytruda) vs pembrolizumab plus chemotherapy in patients with previously untreated, locally advanced, inoperable, or metastatic TNBC whose tumors expressed PD-L1 with a combined positive score of at least 10.5 This randomized, open-label study is assessing PFS per RECIST 1.1 criteria as the primary end point, with secondary end points including OS, ORR, and safety.

Topline results shared in April 2025 showed a statistically significant improvement in PFS with sacituzumab govitecan plus pembrolizumab compared with pembrolizumab plus chemotherapy in this PD-L1–positive population.6 An early trend toward improved OS was also observed, although data remain immature. The safety profile of the combination was consistent with the known profiles of each agent.

These results represent the first demonstration of clinical benefit from an antibody-drug conjugate (ADC) combined with an immune checkpoint inhibitor in the frontline setting for metastatic TNBC, building on prior efficacy data for sacituzumab govitecan in the relapsed/refractory setting. Currently, sacituzumab govitecan is the only FDA-approved TROP-2–targeted ADC with a survival benefit in 2 metastatic breast cancer subtypes.

Comprehensive results from this study will be shared at ASCO and presented to regulatory authorities.

LBA1000:Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: results of the global, randomized, phase 3 VERITAC-2 study.

Session time: Sunday, May 31st, 1:15– 4:15pm CDT

The VERITAC-2 trial is a global, open-label, randomized study evaluating the efficacy and safety of vepdegestrant (ARV-471), an investigational oral Proteolysis Targeting Chimera estrogen receptor (ER) degrader, compared with fulvestrant (Faslodex) in patients with ER-positive, HER2-negative advanced or metastatic breast cancer.7 The trial enrolled patients who had previously received a CDK 4/6 inhibitor plus endocrine therapy. Patients were randomly assigned to receive either vepdegestrant orally once daily or fulvestrant administered. The primary end point was PFS assessed by BICR in both the intent-to-treat (ITT) population and the ESR1-mutant subpopulation. Key secondary end points included OS, ORR, DOR, clinical benefit rate, safety, and PROs.

In February 2024, the FDA granted fast track designation to vepdegestrant as monotherapy for ER-positive, HER2-negative locally advanced or metastatic breast cancer with prior exposure to endocrine-based therapy.8

Topline data announced in March 2025 revealed that the VERITAC-2 trial met its primary end point in the ESR1-mutant population, demonstrating a statistically significant and clinically meaningful improvement in PFS for patients treated with vepdegestrant vs those receiving fulvestrant.9 The observed benefit exceeded the prespecified target hazard ratio of 0.60 in the ESR1-mutant subgroup. However, the trial did not achieve statistical significance in PFS improvement within the overall ITT population.

Vepdegestrant was well tolerated, with a safety profile consistent with prior studies, and no new safety signals were identified.

Want to learn more about why these abstracts are generating buzz? Check out this preview article featuring exclusive expert insights, and visit our conference coverage page for real-time updates on these presentations and more throughout the meeting.

References

1. Trastuzumab deruxtecan (T-DXd) with or without pertuzumab versus taxane, trastuzumab and pertuzumab in HER2-positive metastatic breast cancer (DESTINY-Breast09). ClinicalTrials.gov. Updated May 6, 2025. Accessed May 15, 2025. https://clinicaltrials.gov/ct2/show/NCT04784715
2. 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 15, 2025. https://www.astrazeneca-us.com/media/press-releases/2025/ENHERTU-fam-trastuzumab-deruxtecan-nxki-plus-pertuzumab-demonstrated-highly-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-THP-as-1st-line-therapy-for-patients-with-HER2-positive-metastatic-breast-cancer.html#!
3. Turner N, Huang-Bartlett C, Kalinsky K, et al. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol. 2023;19(8):559-573. doi:10.2217/fon-2022-1196
4. Camizestrant demonstrated highly statistically significant and clinically meaningful improvement in progression-free survival in 1st-line advanced HR-positive breast cancer with an emergent ESR1 tumour mutation in SERENA-6 phase III trial. News release. AstraZeneca. February 26, 2025. Accessed May 15, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/camizestrant-improved-pfs-in-1l-hr-breast-cancer.html
5. Study of sacituzumab govitecan-hziy and pembrolizumab versus treatment of physician’s choice and pembrolizumab in patients with previously untreated, locally advanced inoperable or metastatic triple-negative breast cancer. ClinicalTrials.gov. Updated December 24, 2024. Accessed May 15, 2025. https://clinicaltrials.gov/study/NCT05382286
6. 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. April 21, 2025. Accessed, May 15, 2025. https://www.gilead.com/news/news-details/2025/trodelvy-plus-keytruda-demonstrates-a-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-previously-untreated-pd-l1-metastatic-trip
7. Hamilton EP, Ma C, De Laurentiis M, et al. VERITAC-2: a Phase III study of vepdegestrant, a PROTAC ER degrader, versus fulvestrant in ER+/HER2- advanced breast cancer. Future Oncol. 2024;20(32):2447-2455. doi:10.1080/14796694.2024.2377530
8. Arvinas and Pfizer’s vepdegestrant receives FDA fast track designation for the treatment of patients with ER+/HER2– metastatic breast cancer. News Release. Arvinas. February 6, 2024. Accessed May 15, 2025. https://ir.arvinas.com/news-releases/news-release-details/arvinas-and-pfizers-vepdegestrant-arv-471-receives-fda-fast
9. Arvinas and Pfizer announce positive topline results from phase 3 VERITAC-2 clinical trial. News Release. Arvinas. March 11, 2025. Accessed May 15, 2025. https://ir.arvinas.com/news-releases/news-release-details/arvinas-and-pfizer-announce-positive-topline-results-phase-3