5 Key Breast Cancer Clinical Trials Shaping Treatment
Key Points
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Updated INAVO120 data further support the use of inavolisib in patients with PIK3CA-mutated, hormone receptor (HR)–positive, HER2-negative, endocrine-resistant advanced breast cancer, particularly those with early disease progression.
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Findings from SERENA-6 suggest a potential paradigm shift supporting preemptively switching therapies prior to progression in patients with emergent resistant ESR1 mutations.
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In VERITAC-2, patients with ESR1-mutated, HR-positive, HER2-negative advanced breast cancer experienced significant benefit from vepdegestrant.
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In DESTINY-Breast09, trastuzumab deruxtecan (T-DXd) plus pertuzumab improved progression-free survival (PFS) versus standard of care taxane, trastuzumab, and pertuzumab (THP) in HER2-positive advanced breast cancer.
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ASCENT-04 trial data showed a benefit with sacituzumab govitecan plus pembrolizumab triple-negative breast cancer (TNBC).
2025 ASCO Annual Meeting Breast Cancer Abstracts
Following the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, Rahul Gosain, MD, MBA, and Rohit Gosain, MD, highlighted five key breast cancer presentations on the Oncology Brothers podcast. The doctors were joined by Erika Hamilton, MD, of Sarah Cannon Research Institute, who served as scientific committee chair for the 2025 ASCO Annual Meeting.
INAVO120 Findings at the 2025 ASCO Annual Meeting
Previously, the primary analysis of INAVO120 led to the FDA approval of first-line inavolisib plus palbociclib and fulvestrant in patients with PIK3CA-mutated, HR-positive, HER2-negative, endocrine-resistant advanced breast cancer.
The trial enrolled 325 patients who had progressed on or within 1 year of completing adjuvant aromatase inhibitor (AI) therapy, which was a unique subgroup of patients with “exceedingly poor risk,” according to Dr. Hamilton.
The ASCO presentation provided the final overall survival (OS) analysis. Over a median follow-up of 34.2 months, the median OS was 34 months (95% CI, 28.4-44.8) in the inavolisib group compared with 27 months (95% CI, 22.8-38.7) in the placebo group (hazard ratio, 0.67; 95% CI, 0.48-0.94; P = .019).
In addition, the updated median PFS was 17.2 months (95% CI, 11.6-22.2) in the inavolisib group versus 7.3 months (95% CI, 5.9-9.2) in the placebo group (hazard ratio, 0.42; 95% CI, 0.32-0.55). Dr. Rahul Gosain noted that hyperglycemia, a class effect of PIK3CA inhibitors, must be kept in mind when using inavolisib in breast cancer treatment.
Camizestrant Swap Data at the 2025 ASCO Annual Meeting
Data from the SERENA-6 trial were presented in a plenary session. The study evaluated swapping to camizestrant plus a CDK4/6 inhibitor prior to disease progression in patients with HR-positive, HER2-negative advanced breast cancer who showed an emergent ESR1 mutation during first-line therapy with an AI plus a CDK4/6 inhibitor.
Dr. Hamilton described the findings as proof of principle for camizestrant but agreed with Dr. Rahul Gosain that questions remain regarding time to second progression (PFS2) and OS benefits. Furthermore, she described changing therapy based on the emergence of a resistance marker like ESR1 mutation prior to progression as a paradigm-shifting approach in breast oncology.
In the study, the investigator-assessed median PFS was 16 months (95% CI, 12.7-18.2) in patients that switched to camizestrant and CDK4/6 inhibitor compared with 9.2 months (95% CI, 7.2-9.5) in patients that continued with AI plus a CDK4/6 inhibitor (adjusted hazard ratio, 0.44; 95% CI, 0.31-0.60; P < .00001).
Second progression was observed in 38 patients in the camizestrant group versus 47 patients in the control group (adjusted hazard ratio, 0.52; 95% CI, 0.33-0.81; P = .0038). However, the PFS2 data should be interpreted with caution, as patients who switched to the camizestrant group had essentially started a second line of therapy while those in the control group were still receiving first-line therapy, Dr. Hamilton said.
While the SERENA-6 data don’t support implementing the preprogression camizestrant strategy immediately, Dr. Hamilton explained that further data will likely validate the approach for patients with HR-positive, HER2-negative advanced breast cancer.
VERITAC-2 at the 2025 ASCO Annual Meeting
Dr. Hamilton was the lead author of the VERITAC-2 trial, which evaluated vepdegestrant, a proteolysis targeting chimera estrogen receptor degrader, against fulvestrant in patients with HR-positive, HER2-negative advanced breast cancer with or without ESR1 mutation or visceral disease.
Eligible patients received a CDK4/6 inhibitor plus endocrine therapy, one or fewer additional endocrine therapy agents, no prior selective estrogen receptor degraders (fulvestrant or elacestrant), and no prior chemotherapy. Patients also had to have benefited from their last line of endocrine therapy for at least 6 months.
The median PFS for patients with ESR1 mutations was 5 months (95% CI, 3.7-7.4) in the vepdegestrant group versus 2.1 months (95% CI, 1.9-3.5) in the fulvestrant group (hazard ratio, 0.57; 95% CI, 0.42-0.77; 2-sided P < .001). The median PFS for all patients was 3.7 months (95% CI, 3.6-5.3) in the vepdegestrant group compared with 3.6 months (95% CI, 2.2-3.8) in the fulvestrant group (hazard ratio, 0.83; 95% CI, 0.68-1.02; 2-sided P = .07).
“Like we’ve seen with other drugs, the benefit was really among those patients that had ESR1 mutations,” Dr. Hamilton said, adding that she would use vepdegestrant in the second line specifically for patients with ESR1 mutations if it becomes available.
She also emphasized the tolerability of vepdegestrant in the trial. Some drugs in the oral selective estrogen receptor degrader class are associated with gastrointestinal side effects, but these were reported by a small proportion of patients in VERITAC-2.
2025 ASCO Annual Meeting Presentation on DESTINY-Breast09
The DESTINY-Breast09 trial investigated first-line T-DXd with or without pertuzumab versus standard of care THP in HER2-positive advanced breast cancer. However, the ASCO presentation did not include data from the T-DXd without pertuzumab group.
The median PFS was 40.7 months (95% CI, 36.5–not calculable [NC]) in the T-DXd plus pertuzumab group compared with 26.9 months (95% CI, 21.8-NC) in the THP group (hazard ratio, 0.56; 95% CI, 0.44-0.71; P < .00001). OS data were shown, but median OS was NC for both groups (hazard ratio, 0.84; 95% CI, 0.59-1.19).
“I think the data are really compelling, so I am planning to use it in the first line,” Dr. Hamilton said. “The bigger question is, am I planning to continue it indefinitely for 3 to 4 years? And I can’t say that I am.” She contrasted T-DXd with THP where chemotherapy is time-limited, which can benefit patient quality of life.
Dr. Hamilton added that she would love to see a trial that evaluated discontinuing T-DXd after several months in patients with HER2-positive advanced breast cancer that achieved a very good partial response.
Sacituzumab Govitecan Findings From the 2025 ASCO Annual Meeting
Sacituzumab govitecan plus pembrolizumab was compared with chemotherapy plus pembrolizumab in previously untreated PD-L1–positive advanced triple-negative breast cancer in the ASCENT-04 trial. The trial followed previous data that showed sacituzumab govitecan significantly improved outcomes in previously treated metastatic TNBC.
The median PFS was 11.2 months (95% CI, 9.3-16.7) in the sacituzumab govitecan group versus 7.8 months (95% CI, 7.3-9.3) in the chemotherapy group (hazard ratio, 0.65; 95% CI, 0.51-0.84; P < .001). Moreover, the 6-month and 12-month PFS rates were 72% (95% CI, 65-77) and 48% (95% CI, 41-56) in the sacituzumab govitecan group compared with 63% (95% CI, 56-69) and 33% (95% CI, 26-40) in the chemotherapy group, respectively.
“I can’t think of reasons that I wouldn’t want to offer my patients [with TNBC] sacituzumab govitecan with pembrolizumab,” Dr. Hamilton said.
OS data from ASCENT-04 were not mature at the time of the ASCO presentation, but Dr. Hamilton cited a press release from the companion ASCENT-03 trial that found positive survival benefits with sacituzumab govitecan in PD-L1–negative patients.
“We don’t have FDA approval yet, but I suspect we are going to see some changes over the next year in guidelines, and most of our first-line triple-negative patients are going to be receiving antibody drug conjugates,” Dr. Hamilton said.