Breast Cancer Experts Bookmark Top Abstracts to Watch at the 2025 ASCO Annual Meeting

As we gear up for the 2025 ASCO Annual Meeting, OncLive® asked breast cancer experts to highlight the research and discussions they’re most excited to see presented at the meeting.

We gathered exclusive insights from:

Alexis LeVee, MD, chief fellow of Hematology & Medical Oncology at City of Hope in Duarte, California

Sarah Sammons, MD, associate director of the Metastatic Breast Cancer Program at Dana-Farber Cancer Institute (DFCI) in Boston, Massachusetts; as well as an assistant professor of medicine at Harvard Medical School

Paolo Tarantino, MD, PhD, a clinical fellow at DFCI

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and the associate director of the Susan F. Smith Center for Women’s Cancers at DFCI; as well as an assistant professor of medicine at Harvard Medical School

From phase 3 data that have been teased in the news to abstracts that will add to discussions regarding shifting standards of care (SOCs), here’s what made these experts’ lists:

Abstract 1015: Treatment rechallenge after trastuzumab-deruxtecan–related interstitial lung disease: A multi-institution cohort study.

Session time: May 30, 2:45-4:15pm CDT

LeVee: There’s a study evaluating rechallenge of fam-trastuzumab deruxtecan-nxki [T-DXd; Enhertu] after grade 1 interstitial lung disease and how patients respond after being rechallenged. A lot of these data will be interesting to try to improve outcomes for patients, both by minimizing toxicity and by better personalizing our therapies.

Abstract 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: May 31, 1:15-4:15pm CDT

Tolaney: [The phase 3] ASCENT-04 trial [NCT05382286] is investigating the combination of sacituzumab govitecan-hziy [Trodelvy]—a TROP-2–directed antibody-drug conjugate [ADC]—in combination with pembrolizumab [Keytruda] compared with chemotherapy of physician’s choice plus pembrolizumab for patients who have metastatic triple-negative breast cancer that’s also PD-L1 positive. [These patients are] getting treated in the first-line setting. We’ve seen a news release from this trial, which has told us that sacituzumab govitecan plus pembrolizumab did lead to an improvement in progression-free survival [PFS] compared with chemotherapy plus pembrolizumab.1 We’re hoping that will become a new first-line option for our patients. We’ve desperately been wanting to improve outcomes for metastatic triple-negative disease, so this could be a really nice improvement for patients in the early-[line] setting.

Abstract 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: June 1, 1:00-4:00pm CDT

Sammons: [The phase 3] SERENA-6 trial [NCT04964934] is exciting because it’s challenging the historic paradigm of how we manage metastatic breast cancer in general. In metastatic breast cancer, we treat patients with a regimen that we know to be the most successful based on clinical trials, and we wait to change their therapy until the disease has developed resistance enough to form new tumors on scans.

SERENA-6, for the first time in a phase 3 registrational capacity, is trying to intervene on the cancer cells before we see radiographic progression, when we see that [patients] are developing mutations of resistance in the blood. This trial is in patients with metastatic estrogen receptor [ER]–positive, HER2-negative breast cancer [who had received a] first-line aromatase inhibitor [AI] and a CDK4/6 inhibitor for at least 6 months [and had undergone] blood testing to look for the emergence of ESR1 mutations, which denote resistance to AIs. If those patients developed an ESR1 mutation and still did not have progression on their scans, then they were randomly assigned to either continue their CDK4/6 inhibitor with the AI, which would be the SOC in current clinical practice, or—based on molecular emergence of an ESR1 mutation—switch early to camizestrant, which is an oral selective estrogen receptor degrader that targets ESR1. [in combination with a CDK4/6 inhibitor].

Can we prolong the PFS if we intervene early in the resistance [development], rather than waiting for [patients] to have disease progression on scans? PFS is the primary end point. We’re all going to want to make sure that not only PFS, but also time to second progression and potentially overall survival [OS], are improved by early switch to this type of strategy. For my patients, one of the best quality of life times that they have in their disease is their time receiving a CDK4/6 inhibitor. I’m hoping to extend the amount of time that patients can stay on their CDK4/6 inhibitor for as long as possible, because after that, we move into cytotoxic and targeted therapies that have more toxicity. [SERENA-6], if positive, is going to open the way for new trial designs and is really of value.

Tarantino: There’s going to be a very cool breast cancer abstract in the plenary session. We [typically] treat patients [with ER-positive breast cancer] in the first-line setting with CDK4/6 inhibitors, and then in the second-line setting with other agents after progression. However, SERENA-6 uses a different approach, one that was derived from a prior phase 3 trial called PADA-1 [NCT03079011], where, instead of waiting for disease progression before moving to second-line treatment for hormone receptor [HR]–positive metastatic breast cancer, you switch treatment upon emergence on circulating tumor DNA [ctDNA] of ESR1 mutations. Approximately 40% of patients have an emergence of ESR1 mutations during first-line treatment.

We’ll see more data from PADA-1 at the 2025 ESMO Breast Cancer Congress before ASCO, but in the SERENA-6 trial, which was announced to be positive, apparently switching to camizestrant upon emergence of an ESR1 mutation, maintaining treatment with a CDK4/6 inhibitor, led to a significant PFS advantage.2 It will be very important to look at the magnitude of benefit from this trial, because we want to understand whether a strategy of monitoring patients with ctDNA assays every 3 months in the absence of progression is advantageous in long-term outcomes, [such as] OS. It will be an important moment to see the benefit of a new drug, camizestrant, but also to understand this new paradigm of following patients with ctDNA [testing] in the absence of progression. [These data could help us] see if switching treatment is advantageous for the most prevalent category of patients we see in the clinic, which is those with metastatic HR-positive breast cancer.

Abstract 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: June 2, 7:30-8:00am CDT

Sammons: We are very excited to finally see the results of [the phase 3] DESTINY-Breast09 trial [NCT04784715], which is challenging the historical [SOC] first-line therapy in HER2-positive metastatic breast cancer that we’ve been using for over a decade now, which is a taxane with trastuzumab [Herceptin] and pertuzumab [Perjeta; THP]. DESTINY-Breast09 is a phase 3 trial that is investigating first-line therapy for these patients with 3 different arms: T-DXd, T-DXd with pertuzumab, or the control arm, which is the historical SOC of THP.

This trial is reportedly positive [according to] a news release, but we really need to see the results.3 They will lead to a lot of open questions in this patient population as to whether T-DXd with or without pertuzumab is superior in terms of PFS, which is the primary endpoint. How long are patients staying on this drug? In this trial, patients receive T-DXd indefinitely until progression or toxicity. There are open questions as to how long we need to continue T-DXd, how well our patients will tolerate T-DXd, and whether it’s truly a superior first-line therapy. Another [finding] I am very interested in seeing is whether we could potentially even consider curing more patients with HER2-positive metastatic breast cancer if we use more effective first-line therapies.

Tolaney: We’ve already seen a news release from this trial, which has told us that at the time of an interim analysis, the combination of T-DXd plus pertuzumab led to a significant improvement in PFS. We’re all excited to see whether that could become a new SOC option for our patients.

Abstract 1032: Quantitative pre-treatment assessment of trastuzumab deruxtecan (T-DXd) antibody target (HER2) and payload target (topoisomerase 1, Topo1) to predict outcomes in metastatic breast cancer (MBC).

Session time: June 2, 9:00am-12:00pm CDT

Tarantino: ADCs bring a lot of opportunity in the field of treating breast cancer, but they also bring some challenges. One key challenge is predicting the activity of ADCs. In most of the phase 3 clinical trials of novel ADCs, the immunohistochemistry [IHC] expression of the target fails to predict the activity [of these agents]. IHC score for HER2 has mostly failed to discriminate responders from nonresponders in T-DXd trials, and the same goes for IHC scores for TROP-2 in sacituzumab govitecan trials. We really need novel biomarkers to better understand how these ADCs work.

At ASCO, a poster will be presented with novel ways to evaluate HER2 expression to predict the activity of T-DXd. In the past, data have been presented with high-sensitivity HER2, which is a quantitative immunofluorescence assay developed at Yale that nicely predicted the activity of T-DXd in a continuous manner. Now at ASCO, we’re going to see data with RPPA, another proteomic assay that predicts the activity of T-DXd. We hope that with multi-institutional effort, we will be able to validate better assays to predict the activity of ADCs. This is really an important unmet need in the field, and we are starting to produce some data here.

Abstract 501: Predicting pathologic complete response (pCR) from clinicopathologic variables and HER2DX genomic test in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): Secondary results from the EA1181/CompassHER2 pCR trial.

Session time: June 2, 3:00-6:00pm CDT

Tolaney: One trial I’ve been really looking forward to is the [phase 2] CompassHER2-pCR trial [NCT04266249]. For patients who get treated in the early-stage setting for HER2-positive disease, the standard, at least in the United States, is usually to give a THP for 6 cycles. However, that therapy is associated with significant toxicities, so we’ve always wondered: Could we just give a taxane with trastuzumab and pertuzumab for 12 weeks, and then if [the patients achieve] a pathologic complete response [pCR], just continue the trastuzumab/pertuzumab antibodies to complete a year? [We thought that might be] sufficient therapy for them because they got a pCR. Smaller studies have shown us that THP can result in very good pCR rates, but [CompassHER2-pCR is a] large cooperative group trial that will be important to see. [The investigators are also examining] a novel biomarker, HER2DX, and associating it with the pCRs in this trial. It will be interesting to see whether the HER2DX assay predicts pCR well.

References

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