Top 10 Findings Shaping the Future of Breast Cancer Care From SABCS 2024

Findings from the phase 2 SOLTI VALENTINE trial (NCT05569811) demonstrated that neoadjuvant patritumab deruxtecan with or without letrozole sustained responses with fewer toxicities compared with multi-agent chemotherapy.

At the 2024 San Antonio Breast Cancer Symposium (SABCS), clinicians in the breast cancer field presented key findings and updates on a wide range of treatment strategies that may improve outcomes across different patient populations. Data from oral presentations and late-breaking sessions revealed potential advancements in the use of investigational antibody drug conjugates (ADCs), biomarkers, surgical interventions, and radiotherapy modalities.

CancerNetwork® covered the latest data from these sessions. Here are the top 10 articles covering potentially practice-changing findings from this year’s SABCS:

#1: Neoadjuvant HER3-DXd Maintains Response Rates with Fewer TRAEs in Breast Cancer

Findings from the phase 2 SOLTI VALENTINE trial (NCT05569811) demonstrated that neoadjuvant patritumab deruxtecan (HER3-DXd) with or without letrozole (Femara) sustained responses with fewer toxicities compared with multi-agent chemotherapy.¹ HER3-DXd monotherapy yielded a pathologic complete response (pCR) rate of 4.0% (95% CI, 0.5%-13.7%) and an objective response rate (ORR) of 70.0% (95% CI, 55.4%-82.1%); the respective rates in the chemotherapy arm were 4.2% (95% CI, 0.1%-21.1%) and 70.8% (95% CI, 48.9%-87.4%). The rates of grade 3 or higher treatment-related adverse effects (TRAEs) were 14.0% with HER3-DXd alone, 14.6% with HER3-DXd/letrozole, and 45.8% with chemotherapy.

According to study author Mafalda Oliveira, MD, PhD, of Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, and of the SOLTI Cancer Research Group, both in Barcelona, Spain, findings from SOLTI VALENTINE support the efficacy of HER3-DXd in early breast cancer and its potential application in the management of high-risk, hormone receptor (HR)–positive, HER2-negative breast cancer.

#2: Olaparib Yields Long-Term Efficacy in BRCA+ HER2-Negative Breast Cancer

Six-year pre-specified analysis findings from the phase 3 OlympiA trial (NCT02032823) showed long-term efficacy with olaparib (Lynparza) vs placebo among those with HER2-negative, high-risk breast cancer harboring BRCA1/2 mutations.² Treatment with olaparib improved various outcomes at 6 years vs placebo, which included invasive disease-free survival (iDFS; HR, 0.65; 95% CI, 0.53-0.78) and distant disease-free survival (DDFS; HR, 0.65; 95% CI, 0.53-0.81).

#3: Fam-Trastuzumab Deruxtecan-nxki Improves Efficacy in Metastatic Breast Cancer

Treatment with fam-trastuzumab deruxtecan-nxki (T-DXd) improved progression-free survival (PFS) vs physician’s choice of therapy (TPC) regardless of endocrine resistance and time to progression (TTP) among patients with HR-positive and HER2-low metastatic breast cancer enrolled on the phase 3 DESTINY-Breast06 trial (NCT04494425).³ Compared with the TPC arm, the T-DXd arm showed improvements in PFS for those with a TTP of less than 6 months (HR, 0.69; 95% CI, 0.43-1.12) or more than 12 months on frontline therapy (HR, 0.67; 95% CI, 0.51-0.88). Additionally, T-DXd prolonged PFS among patients with primary endocrine resistance (HR, 0.57; 95% CI, 0.42-0.77) and those with secondary endocrine resistance (HR, 0.68; 95% CI, 0.55-0.84).

#4: Surgical Intervention Improves Efficacy in Young Patients with Breast Cancer

Intervention with risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO) improved various efficacy outcomes among patients 40 years or younger with BRCA-mutated disease.⁴ For patients who underwent RRSO, data showed improvements in the risk of DFS (adjusted HR [aHR], 0.58; 95% CI, 0.52-0.65), breast cancer-free interval (BCFI; aHR, 0.55; 95% CI, 0.48-0.62), and overall survival (OS; aHR, 0.65; 95% CI, 0.53-0.78). RRSO also reduced risks associated with BCFI (aHR, 0.65; 95% CI, 0.57-0.74), DFS (aHR, 0.68; 95% CI, 0.61-0.77), and OS (aHR, 0.58; 95% CI, 0.47-0.70).

#5: Specific Biomarkers Confer Higher pCR/EFS in Triple-Negative Breast Cancer

Data from the phase 3 KEYNOTE-522 study (NCT03036488) showed that patients with high-risk early triple-negative breast cancer (TNBC) harboring biomarkers such as T-cell inflamed 18-gene expression profiles experienced improvements in pCR and event-free survival (EFS) regardless of the receipt of pembrolizumab (Keytruda).⁵ Additionally, tumor mutational burden correlated with improved EFS among patients who received pembrolizumab/chemotherapy (P ≤.001).

#6: Immediate Surgery Lowers Local Recurrence in Older Breast Cancer Population

Based on findings from a meta-analysis, administering immediate surgery significantly reduced local recurrence among elderly patients with breast cancer compared with delaying surgery until after disease progression.⁶ The risk of isolated local recurrence at 5 years reduced with immediate surgery plus tamoxifen (Soltamox) among patients with node-negative disease (rate ratio [RR], 0.25; 95% CI, 0.19-0.34; P <.00001) and node-positive disease (RR, 0.18; 95% CI, 0.11-0.29; P <.00001).

#7: Real-World Data Show No OS Difference Among CDK4/6 Inhibitor Combos in HR+/HER2– MBC

Findings from the retrospective real-world P-VERIFY study (NCT06495164) highlighted no significant OS improvements with 3 CDK4/6 inhibitor regimens as first-line therapy for patients with HR-positive/HER2-negative metastatic breast cancer.⁷ Using unadjusted and adjusted methodologies, investigators observed no significant differences in OS outcomes among patients palbociclib (Ibrance), ribociclib (Kisqali), or abemaciclib (Verzenio) in combination with an aromatase inhibitor.

#8: Tamoxifen Shows Significant Reduction in Overall Recurrence in Breast Cancer

An ancillary analysis of the phase 3 NRG/RTOG 9804 trial (NCT00003857) and the phase 3 ECOG-ACRIN E5194 trial (NCT00002934) showed that the 15-year rate of ipsilateral breast recurrence (IBR) significantly decreased among patients who received tamoxifen for ductal carcinoma in situ (DCIS).⁸ Data showed a statistically significant reduction in the risk of IBR at 15 years with tamoxifen (HR, 0.52; 95% CI, 0.35-0.77; P = .001).

#9: Active Monitoring Noninferior to Standard Surgery, RT in Low-risk DCIS

The rate of ipsilateral invasive cancer was noninferior with active monitoring vs guideline concordant care (GCC) among patients with DCIS enrolled on the COMET trial (NCT02926911).⁹ At 2 years, the rate of ipsilateral invasive cancer was 5.9% (95% CI, 3.71%-8.04%) in the GCC arm vs 4.2% (95% CI, 2.31%-6.00%) of those who received active monitoring.

#10: Exclusive Radiation Therapy Improves QOL and Safety Outcomes in Breast Cancer

Findings from the phase 3 EUROPA trial (NCT04134598) showed that health-related quality of life (HRQOL) improved with exclusive postoperative radiotherapy vs endocrine therapy for patients with stage I luminal-like breast cancer.¹⁰ Additionally, exclusive radiotherapy reduced the incidence of treatment-related treatment-emergent AEs (67.0%) compared with endocrine therapy (85.4%).

References

1. Oliveira M, Pascual T, Parraga KA, et al. Neoadjuvant HER3-DXd alone or in combination with letrozole for high-risk HR+/HER2- early EBC: Primary results of the randomized phase II SOLTI VALENTINE trial. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. LB1-06.
2. Garber, J. OlympiA- Phase 3, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients w/ germline BRCA1/BRCA2 pathogenic variants & high risk HER2-negative primary breast cancer; longer term follow-up. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. GS1-09
3. Bardia A, Hu X, Dent R, et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: additional analysis from DESTINY-Breast06. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. LB1-04.
4. Lambertini M, Sonnenblick A, Agostinetto E, et al., Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: results from an international cohort study. Presented at the 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. GS1-08.
5. O’Shaughnessy J. Exploratory biomarker analysis of the phase 3 KEYNOTE-522 study of neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage TNBC. Presented at the 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. LB1-07.
6. Hills RK, Bradley R, Braybrooke J, et al. Immediate breast surgery versus deferral of surgery in women aged 70+ years with operable breast cancer: patient-level meta-analysis of the three randomised trials among 1,082 women. Presented at the 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. LB1-01.
7. Rugo HS, Layman RM, Lynce F, et al. . Comparative overall survival of CDK4/6 inhibitors plus an aromatase inhibitor (AI) in HR+/HER2– MBC in the US real-world setting. Presented at the 2024 San Antonio Breast Cancer Symposium; San Antonio, TX; December 10-14, 2024. PS2-03.
8. Wright JL. Impact of tamoxifen only after breast conservation surgery for “good risk” duct carcinoma in situ: results from the NRG oncology/RTOG 9804 and ECOG-ACRIN E5194 trials. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-14, 2024; San Antonio, TX. GS2-02
9. Hwang ES, Hyslop T, Lynch T, et al. Early oncologic outcomes following active monitoring or surgery (+/- radiation) for low risk DCIS: the comparing an operation to monitoring, with or without endocrine therapy (COMET) study (AFT-25). Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-13, 2024; San Antonio, TX. GS2-05.
10. Meattini M, Carmen De Santis M, Visani L, et al. Exclusive endocrine therapy or radiation therapy in women aged 70+ years with luminal-like early breast cancer (EUROPA): preplanned interim analysis of a randomized phase 3 trial. Presented at: 2024 San Antonio Breast Cancer Symposium; December 10-14; 2024; San Antonio, TX. GS2-02.