ESMO 2025 Congress on October 17–21, 2025.
Capivasertib plus fulvestrant as first- and second-line endocrine-based therapy in PIK3CA/AKT1/PTEN-altered hormone receptor–positive advanced breast cancer: subgroup analysis from the Phase III CAPItello-291 trial. Researchers analyzed data from the Phase III CAPItello-291 trial to determine the efficacy and safety of capivasertib plus (+) fulvestrant in the treatment of hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer based on line of endocrine therapy (ET). Eligible patients had HR+, HER2– advanced breast cancer with disease progression during or after (≤12 months) (neo)adjuvant aromatase inhibitor (AI) therapy (first-line ET) or while receiving previous AI-based therapy for advanced breast cancer (second- or third-line ET). Patients were randomized 1:1 to capivasertib+fulvestrant or placebo+fulvestrant. Capivasertib 400mg was taken twice daily, four days on, three days off. Fulvestrant 500mg was administered intramuscularly on Days 1 and 15 of Cycle 1 and Day 1 of each subsequent 28-day cycle. Among 236 patients with PIK3CA/AKT1/PTEN alterations who had not been previously treated with chemotherapy, 32 were in the first-line ET group and 185 were in the second-line ET group; 12 and 106 patients, respectively, were randomized to capivasertib+fulvestrant and 20 and 79 patients, respectively, were randomized to placebo+fulvestrant. Additionally, in the second-line ET subgroup, 155 patients (88 in the capivasertib arm, 67 in the placebo arm) had received cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment for advanced breast cancer. Progression-free survival (PFS) was prolonged in the capivasertib+fulvestrant arms across ET lines. In the first-line ET group, median PFS (95% confidence interval [CI]) was 14.3 (5.4–noncalculable) months in the capivasertib+fulvestrant arm compared to 3.7 (1.7–11.7) months in the placebo+fulvestrant arm (hazard ratio [HR]: 0.43, 95% CI: 0.17–1.01). In the second-line ET group, median (95% CI) PFS was 7.2 (5.4–9.1) months in the capivasertib+fulvestrant arm versus 3.1 (2.0–3.7) months in the placebo+fulvestrant arm (HR: 0.56, 95% CI: 0.40–0.77). Similarly, in the second-line post-CDK4/6 inhibitor subgroup, median (95% CI) PFS was 7.0 (5.4–8.5) with capivasertib+fulvestrant versus 2.6 (1.8–3.5) months with placebo+fulvestrant (HR: 0.5, 95% CI: 0.35–0.71).
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The association between initial metastatic site and overall survival of patients with single-organ HER2+ metastatic breast cancer (mBC): a real-world SONABRE study. In this study, researchers aimed to determine whether site of single-organ metastasis significantly impacted overall survival (OS) among patients with HER2+ metastatic breast cancer (MBC). Data from patients diagnosed between 2007 and 2022 were included for analysis. Metastatic sites with fewer than 10 patients were excluded. Among 931 patients, 377 (40.5%) had single-organ metastases; after excluding metastatic sites with fewer than 10 patients, there were 366 patients included for analysis. Median age was 59.3 years. Most patients had nonlobular histology (90.4%) and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1 (66.1%). A total of 59.3 percent of patients had recurrent MBC. Most patients (64.2%) received first-line treatment with a HER2-targeted therapy. Factors associated with decreased OS included poor ECOG PS (≥2 vs. 0/1, HR: 3.36), older age (≥75 vs. <50 years, HR: 2.26), and metastatic-free interval (3–60 vs. <3 months, HR: 1.62). The most common site of metastasis was bone (n=181), followed by liver (n=66), lymph nodes (n=43), lung (n=41), brain (n=21), and pleura (n=14). Patients with lung-only metastasis had significantly longer median OS compared to those with bone-only metastasis (68.8 vs. 52.1 months; adjusted HR: 0.47, 95% CI: 0.28–0.78, p=0.003). OS for the remaining metastatic locations did not significantly differ from bone-only metastasis.
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Challenging the prognostic role of classical vs. nonclassical histology in metastatic lobular breast cancer. Nonclassical histology in metastatic invasive lobular carcinoma (ILC) is often perceived as aggressive disease, despite limited evidence. Therefore, in this retrospective analysis, researchers aimed to determine the prognostic relevance of nonclassical histology in metastatic ILC. Data from 2007 to 2022 were analyzed. Among 218 patients with metastatic ILC, median age was 54 years, and most patients (62.4%) were postmenopausal. In the overall cohort, median PFS and OS were 14.8 and 32.7 months, respectively. Fifty-three patients had nonclassical histology, and 148 had classical histology. Median PFS was 15.4 and 13.8 months in the classical and nonclassical histology groups; this difference was not significant (HR: 1.04, 95% CI: 0.74–1.47, p=0.854). Similarly, median OS was comparable between groups, at 32.8 months for patients with classical histology and 35.5 months for those with nonclassical histology (HR: 0.98, 95% CI: 0.66–1.44, p=0.916). Additionally, PFS and OS did not significantly differ based on other factors, including disease presentation, immunophenotype, number of metastases, and histologic pattern. This study showed that metastatic ILC with nonclassical histology was not associated with poor survival and therefore should not guide risk stratification or treatment intensity.
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Clinical and molecular characteristics of cancers that switch phenotype from ER+ primary to triple-negative in metastatic disease. About 20 percent of estrogen receptor–positive (ER+) breast cancers undergo ER loss at relapse. In this study, researchers compared characteristics of cases of phenotype switch (Switch) to cases that remain ER+ or triple-negative. Data from 34 Switch, 190 ER+, and 58 triple-negative cases were analyzed. In the primary setting, Switch cases had lower ER expression compared to ER+ cases (median H score: 115 vs. 200, p=0.039); other clinical characteristics were similar between groups. HER2-enriched and basal-like intrinsic subtypes composed a greater proportion of Switch primary cancers compared to primary ER+ and triple-negative cases; in the recurrent setting, a significantly greater proportion of Switch tumors were HER2-enriched subtype, compared to ER+ and triple-negative tumors (57% vs. 11% and 16%; p=0.001 and 0.003, respectively). Nodal metastasis was more common and bone metastasis less common in Switch cases versus ER+ cases. Twenty patients (59.0%) with Switch tumors developed triple-negative disease at recurrence, with the remainder receiving ET treatment before undergoing triple-negative biopsy; compared to the latter group, patients with triple-negative disease at recurrence had significantly longer disease-free survival (DFS; 8 vs. 4 years, p=0.011) and OS (13 vs. 8 years, p=0.0013). Tumor mutational burden was increased in Switch versus ER+ tumors (166Mut/MB vs. 44Mut/MB, p=0.02), and APOBEC mutational signatures were enriched in Switch versus triple-negative tumors (p=0.012).
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Real-world study on rates of positivity for ESR1, PIK3CA, PTEN, and AKT1 among patients with ER+, HER2– metastatic breast cancer. Testing for ESR1, PIK3CA, PTEN, and AKT1 biomarkers is recommended at breast cancer progression following ET. In this study, researchers evaluated the real-world positivity rate of these alterations in ER+, HER2– MBC. Data from adult patients who initiated a subsequent line of therapy between February 1, 2023, and December 31, 2024, were eligible for inclusion. All patients received next-generation sequencing (NGS) test results. A total of 636 patients, 98 percent of whom were female, were included for analysis. Median age was 68 years at the start of treatment following ET. Of the studied biomarkers, the positivity rate was highest for PIK3CA, at 37 percent (n=238). Twenty-four percent of patients (n=155) had ESR1 positivity, 18 percent (n=112) had PTEN positivity, and four percent (n=27) had AKT1 positivity. The rate of ESR1 and PIK3CA, PTEN, or AKT1 comutation was 15 percent (n=94). Overall, about half of patients (48%, n=306) harbored PIK3CA, PTEN, or AKT1 mutations, regardless of ESR1 mutation status. This real-world study highlights the importance of NGS use in order to identify actionable mutations in MBC.
Access abstract here: https://oncologypro.esmo.org/congress-resources/esmo-congress-2025?presentation=real_world_study_on_rates_of_positivity_for_esr1__
Metastatic breast cancer in pregnancy: treatment and maternal-neonatal outcomes. This single-center study describes treatment and outcomes among pregnant patients with MBC. Among 20 patients, median age was 35 years (range: 23–43 years). The most common histological type was invasive ductal carcinoma, present in 17 patients; among these patients, six had luminal B disease, six had basal cell–like disease, three had HER2+ disease, and two had luminal A disease. One patient each had ILC, invasive papillary carcinoma, and phyllodes malignant tumor. Thirteen patients underwent chemotherapy during gestation. Sixteen pregnancies progressed to delivery; two patients underwent therapeutic termination of pregnancy, and two patients experienced stillbirth. Mean gestational age at delivery was 34.1 weeks (range: 28–38.1 weeks). Mean birth weight was mean birth weight was 1,931g (955–2,750g), and no malformations occurred. Following receipt of neonatal care, all infants were discharged. During the follow-up period (median follow-up: 12.7 months), 11 patients had died due to disease progression, five patients had discontinued treatment, and four were still receiving treatment. Survival rates at 12, 24, and 36 months post-metastatic diagnosis were 72.4, 65.8, and 45.1 percent, respectively.
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Distinct metastatic patterns and diagnostic utility of CA 15-3 in lobular versus ductal breast cancer: a retrospective population-based study. In this retrospective cohort study, researchers evaluated metastatic patterns in lobular breast cancer (LBC) and ductal breast cancer (DBC), as well as the diagnostic utility of CA 15-3 in metastatic LBC versus DBC. Data from 542 patients diagnosed with metastatic LBC or DBC from 2009 to 2020 were analyzed; 417 patients (81%) had DBC, and 125 (19%) had LBC. Ninety-five percent of patients with LBC had ER+ disease, compared to 77 percent of those with DBC. HER2 positivity was more prevalent in DBC (21%) compared to LBC (4%). The most common sites of metastasis were bone, liver, and lung, though distribution varied between groups. Eighty-two percent of patients with LBC had bone metastasis, 31 percent had liver metastasis, and 15 percent had lung metastasis. Among those with DBC, bone was also the most common site of metastasis (68%), but the distribution of liver and lung metastases was similar (49% and 47%, respectively). Compared to patients with DBC, a significantly greater proportion of patients with LBC had ureteropelvic (20% vs. 2.7%), gynecological (4.0% vs. 1.6%), and gastrointestinal (5.6% vs. 1.4%) metastases. Twenty-eight percent of patients with LBC had ascites, compared to only 5.5 percent of those with DBC. CA 15-3 was determined to have diagnostic value in 76 and 68 percent of LBC and DBC cases, respectively. Ninety-six percent of ureteropelvic metastases were detected with CA 15-3, compared to only four percent with computed tomography (CT). Among patients with ER+, HER2– disease, median OS was shorter in LBC compared to DBC (3.5 vs. 4.3 years, p=0.021). Patients with LBC showed a greater prevalence of metastases that are often underdiagnosed with imaging alone, such as ureteropelvic metastases; furthermore, CA 15-3 showed diagnostic utility in detecting such metastases in LBC.
Access abstract here: https://oncologypro.esmo.org/congress-resources/esmo-congress-2025?presentation=distinct_metastatic_patterns_and_diagnostic_utilit