Royal Derby Hospital,University Hospitals of Derby and Burton NHS Foundation Trust

INTRODUCTION:We aimed to assess diagnostic performance and accuracy for local staging of CEM combined with DBT (CE + DBT) compared to digital mammography (DM) and MRI. METHODS:Female patients aged 18-70 years with clinical or sonographic suspicion of breast cancer had CE + DBT and breast MRI prior to treatment. Diagnostic accuracy, ability to identify additional disease foci, and disease extent estimations were compared for all imaging techniques. Histopathology was the reference standard. RESULTS:Eighty-seven participants were recruited; 80 included in the study; 69 had cancer. DBT had greater diagnostic sensitivity than DM, but lowest specificity. CEM and CE + DBT showed 100% sensitivity. Specificity was lower for CE + DBT than CEM alone. MRI sensitivity was higher than DM or DBT, but lower than CEM or CE + DBT. MRI specificity was lower than CE-DBT, both separately and in combination. Thirty-nine patients were included in exploratory subset analysis regarding identifying additional foci. DM missed the most cases (8/10); DBT had higher sensitivity but lower specificity; MRI s sensitivity but with more false positives; CEM had the greatest overall accuracy. Thirty patients were included in unifocal disease extent analysis. MRI, CEM, and CE-DBT all demonstrated strong correlation with pathological size, with MRI showing closest agreement. CONCLUSIONS:Combined CE + DBT is feasible within a one-stop clinic appointment and may obviate the need for MRI. CEM demonstrated comparable accuracy to MRI, both for diagnostic accuracy and in local staging. We showed no clear benefit to combining morphological information derived from DBT with functional data of CEM compared to CEM alone.

Neratinib, a pan-HER tyrosine kinase inhibitor, is approved in Europe as extended adjuvant therapy for HR+/HER2+ early breast cancer (EBC) in patients who have completed trastuzumab-based therapy ≤ 1 year ago. In this population, the ExteNET trial for patients with HR+/HER2+ EBC demonstrated a clinical benefit for neratinib vs. placebo, including significantly improved 5-year invasive disease-free survival (iDFS) (iDFS; Δ5.1%, HR 0.58, 95% CI 0.41-0.82). Neratinib-associated diarrhoea was the most common adverse event (39% Grade 3 without mandatory prophylaxis). Real-world data are essential for informing the management of diarrhoea and understanding patterns within its approved indications. NERLYFE is a European, prospective, observational post-authorization safety study (PASS) conducted in routine clinical practice across Austria, Czech Republic, Germany, and the United Kingdom. Patients with HR+/HER2+ EBC were scheduled to receive neratinib as extended adjuvant therapy for up to 12 months in accordance with the EU SmPC. The primary objective is to describe the incidence of permanent treatment discontinuation due to diarrhoea during the first 3 months (mo) of neratinib treatment (core phase). Secondary objectives include describing the pattern of diarrhoea and maintenance of neratinib treatment. At data cut-off on 31 December 2024, 113 patients received at least one dose of neratinib and were observed for at least 3 months. Results of this pre-planned interim analysis are reported. Baseline characteristics were median age 55 years, 86% ECOG PS 0, 79% high risk of recurrence (AJCC stage > I or N+ or non-pCR after neoadjuvant treatment). Overall, 56%, 28% and 11% of patients received adjuvant/post-neoadjuvant trastuzumab monotherapy, trastuzumab-emtansine (T-DM1), and trastuzumab/pertuzumab, respectively, with 5% of patients receiving other anti-HER2 therapy. The initial dose of neratinib was 240 mg/day for 61% of patients and < 240 mg/day for 39%; 63% of patients received anti-diarrhoeal prophylaxis at least once. Fourteen percent of patients permanently discontinued neratinib due to diarrhoea within the first 3 mo of neratinib treatment, primarily within the first 2 mo of treatment. The diarrhoea-related neratinib discontinuation rate was lower in patients who received anti-diarrhoeal prophylaxis vs. those who did not (10% vs. 21%) and in those who started below vs. at 240 mg/day (12% vs. 15%). Any grade diarrhoea occurred in 88% of patients (20% Grade 3): 86% and 91% in the prophylaxis/non-prophylaxis groups respectively, and 82% vs. 91% in the below vs. at 240 mg/day group. No Grade 4 or 5 event was reported. Median time to first diarrhoea was within the first 7 days. Among patients receiving prophylaxis, the median cumulative duration of Grade ≥3 diarrhoea was 6.5 days versus 13 days without prophylaxis. Corrective treatment was used in 66% of patients. Treatment-emergent adverse events (TEAEs) other than diarrhoea were reported in 55% of patients, mostly Grade 1-2 gastrointestinal events. Three patients experienced serious TEAEs, including one diarrhoea event. Anti-diarrhoeal prophylaxis was associated with a reduction in the incidence of diarrhoea occurrence (any grade), rate of neratinib discontinuation, and duration of Grade ≥3 diarrhoea. The overall safety profile of neratinib was consistent with the EU SmPC. These real-world findings support the benefit of anti-diarrhoeal prophylaxis and the use of neratinib in HR+/HER2+ early breast cancer patients in the current treatment landscape. D. Baerens, A. Waqas, G. Dagmar, A. Jegannathen, T. Sarkodie, P. Seropian, V. Bjelic-Radisic, M. Elnaggar, P. Staib, B. Lex, N. Harbeck, C. Jackisch, M. Schmidt, J. Suissa, A. Zkik, O. Dialla, R. Bartsch. A real-world prospective observational multi-national study in adult patients with breast cancer treated with extended adjuvant neratinib: interim results from the NERLYFE study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-11-21.

e19507 Background: Elranatamab is a B-cell maturation antigen–CD3 bispecific antibody approved for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) in several countries. The efficacy and safety of elranatamab were demonstrated in previous clinical trials, and real-world data for elranatamab are currently being accumulated. This interim analysis provides an early look into the results from a real-world primary data collection study of elranatamab in patients with RRMM. Methods: MagnetisMM-16 (EUPAS106401) is a prospective, international, multicenter, non-interventional post-authorization safety study evaluating the effectiveness and safety of elranatamab in patients aged ≥18 years with RRMM treated in real-world settings. Patients are being recruited from hematology/oncology clinics, primary care settings, and academic centers in the United Kingdom, Germany, Spain, and Italy. Investigators were asked in the study protocol to follow recommendations in the local health authority–approved product label, including infection precautions and antimicrobial prophylaxis. This interim analysis is based on a September 15, 2025 data cut and describes preliminary results. Results: A total of 52 patients were included in the analysis. The median age of patients was 70.0 years (range, 48.0-87.0), 59.6% were male, and 88.5% were white. The patients were heavily pre-treated with more than half of the patients (61.5%) receiving ≥4 prior lines of therapy, 94.2% were double-class exposed to prior anti-CD38 and proteasome inhibitor, and 84.6% were triple-class exposed to prior anti-CD38, proteasome inhibitor, and immunomodulatory therapy. International Staging System disease stage at baseline was reported for 32 patients, 46.9% (n=15) had stage III and 34.4% (n=11) had stage II disease. The most common (≥10%) comorbidities were hypertension (32.6%), atrial fibrillation (16.3%), chronic kidney disease (11.6%), and type 2 diabetes mellitus (14.0%). Conclusions: Real-world effectiveness and safety data for elranatamab will be presented for this heavily pre-treated RRMM patient population at the congress. Clinical trial information: EUPAS106401.

Abstract Background Inobrodib (CCS1477/Ino) is a first-in-class potent, selective, and orally bioavailable inhibitor of the bromodomains of p300 and CBP, two closely related histone acetyl transferases with oncogenic roles in hematological malignancies. Inobrodib exhibits potent anti-tumor cell activity in a range of cell lines including multiple myeloma and demonstrates synergistic activity with pomalidomide (Pom). The combination of Ino with Pom and dexamethasone (dex) (InoPd) was previously shown to have a manageable safety profile and activity in patients (pts) with heavily pretreated RRMM. Aims To determine the optimal dose (RP2D) of InoPd in pts with RRMM (NCT04068597). Methods Eligible pts have confirmed RRMM and must have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. Patients are randomised to 3 different dose levels of inobrodib (20mg, 30mg, 40mg) BID on a 4 days on/3 days off intermittent schedule with Pom 4 mg and dex 20-40mg depending on age, all administered on 28-day cycles. Randomization is stratified based on Pom-refractory status. Adverse events are graded by CTCAE v5.0 and responses are investigator-assessed per IMWG criteria. Pharmacodynamic profiling of paired bone marrow samples and serial peripheral blood mononuclear cell samples, using mass cytometry for IRF4, MYC, and other markers is ongoing. Results Recruitment is ongoing, with 36 of 60 (60%) planned patients enrolled as of the data cut-off (7 July 2025); full enrollment is expected by September 2025. Initial data combining all three dose levels are summarized below. Comprehensive dose-specific data for all patients will be presented at the conference. There are 26 pts in the safety set (received at least one dose), with a median age of 70 yrs (range 44-81). Median number of prior lines of therapy is 5 (range 2-12), 84.6% are triple-class exposed, 15 pts (57.7%) are triple class refractory, and 4 pts (15.4%) received prior BCMA/TCE therapy. In addition, 12 pts (46.2%) were Pom-refractory. Grade (gr) 3/4 treatment-emergent adverse events (TEAEs) have been reported in 11 of 26 (42%) patients and are predominantly hematologic (neutropenia 15.4%; thrombocytopenia 7.7%; anemia 3.8%). Of note, the main potential overlapping toxicity of this triplet was thrombocytopenia, but there has been no increased frequency or severity to date. Inobrodib monotherapy has not been shown to cause neutropenia. Grade 3/4 infections were uncommon (3.8%), and consistent with the anticipated safety profile of Pom/dex alone. There are currently 16/26 pts evaluable for response assessment as 10 pts have not yet had a post-baseline efficacy assessment as they were too recently enrolled. To date, responses ≥ PR (including unconfirmed) have been reported in 12/16 (75%) of pts. Responses have been observed in pts refractory to Pom and previously exposed to anti-BCMA and TCE therapies. Median time on treatment was 38.5 days (range 4-106 days). To date, only one pt in the 20mg cohort had discontinued the study to progressive disease and death. Mature data will be presented at the conference. Summary: Preliminary results confirm earlier findings that the combination of InoPd has both a manageable safety profile and extremely promising clinical activity in a heavily pretreated population, including those who have received anti-BCMA and/or TCE therapies, and have previously received Pom. Updated results on efficacy and safety for the full cohort will be presented at the meeting. Results from this study will inform the dose for registrational studies, and additional arms on this trial investigating inobrodib in combination with elranatamab and teclistamab are currently ongoing and enrolling.

To assess the association of transaortic flow-rate (TFR) with symptom-driven aortic valve replacement (AVR) in asymptomatic patients with moderate to severe aortic stenosis (AS). PRIMID was a prospective, multi-centre observational study. Patients with asymptomatic moderate to severe AS underwent transthoracic echocardiography (TTE), cardiopulmonary exercise testing and stress cardiovascular magnetic resonance (CMR) imaging. TFR was calculated as stroke volume divided by left ventricular ejection time. Patients were followed-up for a minimum of one-year initially. The primary outcome was symptom-driven AVR. Long-term follow-up data was obtained through electronic health records. The secondary outcome was long-term major adverse cardiovascular events (MACE) defined as cardiovascular mortality and hospitalisation with heart failure, myocardial infarction, syncope or arrhythmia. We included 171 individuals: mean age 66.21±3.43 years, 76