trastuzumab/pertuzumab (EG13084) / EirGenix - LARVOL DELTA

EMILIA and DESTINY: Real-World Sequencing Insights in a HER2-positive Metastatic Breast Cancer with Rare Pancreatic metastasis (ESMO Asia 2025) - "In an attempt to render her no evidence of disease (NED), MDT pursued mastectomy (ypTis) and chest wall radiotherapy, followed by maintenance trastuzumab pertuzumab 1 year...Gemcitabine bridging was administered during visceral crisis, after which trastuzumab emtansine (TDM-1) was commenced, achieving stable disease with marginal regression sustained over six cycles...Repeated biopsy was critical to exclude a second primary and reaffirm HER2 status, enabling optimal therapeutic choice. These observations support further investigation into post–T-DXd sequencing strategies and may inform management of biologically similar patient subgroups in ongoing and future trials."

Clinical • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ER • HER-2 • PGR

Preliminary efficacy and safety of TQB2102 in HER2-positive locally advanced unresectable or metastatic biliary tract cancer: Phase Ib study results (ESMO Asia 2025) - P1/2 | "Notably, in Cohort 1, the ORR was 28.6% (95% CI: 3.7–71.0) in pts with prior anti-HER2 therapy( Trastuzumab,Pertuzumab,DS-8201) and 50% (95% CI: 6.8–93.2) in HER2 IHC 2+ and ISH+ pts. TQB2102 demonstrated favorable tolerability and encouraging antitumor activity in HER2-positive locally advanced/metastatic BTC. The 7.5 mg/kg dose showed superior efficacy versus 6.0 mg/kg and is therefore recommended as the RP2D for BTC. The Phase 2 study is currently in preparation."

Clinical • Metastases • P1 data • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • CD4 • HER-2

Pertuzumab versus pyrotinib in combination with trastuzumab and taxanes for first-line (1L) treatment of patients with HER2–positive metastatic breast cancer (HER2+MBC): A multicenter real-world study (ESMO Asia 2025) - "Background: The CLEOPATRA study established taxane+trastuzumab+pertuzumab(THP)as the 1L standard for HER2+ MBC over a decade ago. The recent PHILA study showed that docetaxel+trastuzumab+pyrotinib (an irreversible pan-HER receptor tyrosine kinase inhibitor ) (THPy) significantly prolonged progression-free survival (PFS)versus placebo group, establishing it as a viable 1L option in China.Given limited comparative evidence, this real-world study aimed to evaluate the effectiveness of THP and THPy in HER2+ MBC patients and identify potential beneficiary populations for each regimen. Patients who were treated with THP or THPy as a 1L treatment between January 2018 and March 2025 were included in this multicenter real-world study... Compared with the THP ,THPy significantly improved PFS in patients with untreated HER2+MBC. Notably, THPy demonstrated superior survival benefits specifically in subgroups with:premenopausal status, ECOG PS 0, de novo stage IV disease, previous..."

Clinical • Combination therapy • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Clinical Outcomes of Trastuzumab Emtansine (T-DM1) Following Trastuzumab Deruxtecan (T-DXd) in Metastatic Breast Cancer: A Single-Center Experience (SABCS 2025) - "Clinical Outcomes of Trastuzumab Emtansine (T-DM1) Following Trastuzumab Deruxtecan (T-DXd) inMetastatic Breast Cancer: A Single-Center ExperienceBackground: HER2-positive metastatic breast cancer (MBC) remains an oncological challenge afterdisease progression to pertuzumab-trastuzumab, and fam-trastuzumab deruxtecan. This study provides real-world evidence of the limited clinical efficacy of T-DM1 following resistant to T-DXd in HER2-positive MBC. Further research is warranted to develop novel therapeutic agents in this subgroup of patients and also to develop strategies to avoid resistant to T-DXd."

Clinical • Clinical data • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Cardiac Monitoring in Patients Receiving HER2-Directed Therapy: A Meta-Analysis and Cost-Effectiveness Analysis (SABCS 2025) - "We conducted a meta-analysis to quantify the risk of cardiotoxicity associated with HER2-directed agents and developed a cost-effectiveness model to evaluate alternative frequency of cardiac monitoring in patients with a standard cardiovascular risk profile. We performed a systematic literature search (Ovid MEDLINE, Embase, Cochrane) and included 55 studies (n=39,335) evaluating trastuzumab, pertuzumab, trastuzumab deruxtecan (T-DXd), and trastuzumab emtansine (T-DM1). HER2-directed therapies are associated with low rates of symptomatic cardiotoxicity, particularly T-DM1 and T-DXd. Cost-effectiveness modeling demonstrated diminishing returns with more frequent LVEF monitoring. Future analyses will assess the cost-effectiveness of LVEF monitoring strategies in patients with early-stage or metastatic disease treated with trastuzumab, T-DM1, or T-DXd."

Cost effectiveness • HEOR • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer

MODULE 2: Previously Untreated HER2-Positive Metastatic Breast Cancer (mBC) (SABCS 2025) - "Sponsored by AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, and Puma Biotechnology Inc. Historical outcomes with standard HER2-targeted therapies for newly diagnosed HER2-positive mBC; rationale for the evaluation of effective later-line HER2-targeted treatments in the front-line setting Early data with T-DXd in combination with pertuzumab as up-front therapy for HER2-positive mBC in the Phase Ib/II DESTINY-Breast07 study Published efficacy and safety findings from the Phase III DESTINY-Breast09 trial documenting the benefit of T-DXd in combination with pertuzumab versus taxane/trastuzumab/pertuzumab as first-line therapy for HER2-positive mBC Emerging positive findings from the Phase III HER2CLIMB-05 study assessing tucatinib versus placebo, both in combination with standard first-line maintenance therapy, after chemotherapy-based induction for HER2-positive mBC"

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Real-world Clinical Outcomes in Patients with HER2+ Metastatic Breast Cancer Treated with Trastuzumab Deruxtecan After One or More Prior Lines of Therapy: Data from U.S Community Oncology Practices (SABCS 2025) - "Clinical outcomes of 1L and 2L rwTTF were examined in an exploratory subgroup of pts with 1L taxane+trastuzumab+pertuzumab based regimen (THP) followed by 2L T-DXd vs. 2L trastuzumab emtansine (T-DM1). The study findings affirm the real-world clinical effectiveness and safety of T-DXd in pts with HER2+ mBC as observed in the DESTINY clinical trials. Despite higher disease and comorbidity burden in this small sample of pts with 2L T-DXd use, longer delays in time to progression and discontinuation were observed compared to later line use of T-DXd; and longer rwTTF compared to 2L T-DM1 use, reinforcing the importance of utilizing T-DXd as early as possible in the treatment pathway to improve long-term pt outcomes."

Clinical • Clinical data • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

ADAPTHER2-IV: NeoAdjuvant Therapy With Trastuzumab-deruxtecan Versus Chemotherapy+Trastuzumab+Pertuzumab in HER2+ Early Breast Cancer (clinicaltrials.gov) - P2 | N=402 | Active, not recruiting | Sponsor: West German Study Group | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2028 ➔ Jun 2029 | Trial primary completion date: Jun 2026 ➔ Jun 2025

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Implications of PIK3CA/HER2 Status and Age/Comorbidities on Clinical Investigators' (CIs) Selection of First-Line Systemic Therapy for Hormone Receptor-Positive (HR+) Metastatic Breast Cancer (mBC) (SABCS 2025) - "A modest honorarium was offered. Ribociclib (R) was the most common CDKi recommended for PIK3CA-wildtype, HER2-negative tumors, including patients with symptomatic visceral and asymptomatic bone metastases (Table). For patients with PIK3CA-mutated tumors with disease relapse 2 years into adjuvant endocrine therapy (ET), respondents most commonly recommended inavolisib (I)/palbociclib (P)/ET, and of great interest, 7 of 20 CIs would recommend this triplet for a patient with de novo disease. For patients with HR+, HER2-positive tumors, P/ET in addition to trastuzumab/pertuzumab was the most common recommendation for postchemotherapy/anti-HER2 maintenance treatment... The clinical practice trend of selecting R as the preferred initial CDKi because of its consistent overall survival benefit has been modified by data from INAVO120 and PATINA, in which the perceived better tolerability of P led to its combination with targeted therapies that significantly improved outcomes...."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Prognostic value of baseline FDG PET/CT in HER2-positive metastatic breast cancer treated with first-line trastuzumab, pertuzumab, and docetaxel. (PubMed, Breast Cancer Res) - No abstract available

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

HER2CLIMB-05: A Phase 3 Study of Tucatinib Versus Placebo in Combination with Trastuzumab and Pertuzumab as First-line Maintenance Therapy for HER2+ Metastatic Breast Cancer. (PubMed, J Clin Oncol) - P3 | "Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC."

Journal • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Multidimensional impact of fixed-dose subcutaneous trastuzumab-pertuzumab on oncology workflow and patient time burden in a real-world study. (PubMed, Breast Cancer) - “Phesgo improves both patient time burden and staff workflow efficiency, supporting more sustainable and patient-centered delivery of HER2-targeted therapy. These findings highlight the broader system-level value of fixed-dose SC regimens in high-volume oncology settings under real-world conditions.”

Journal • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Retrospective analysis of survival of patients with HER2-positive breast cancer with microscopic residual invasive disease after neoadjuvant chemotherapy. (PubMed, Breast Dis) - "However, the extent of benefit T-DM1 will provide over trastuzumab plus pertuzumab (HP) in patients with microscopic residual invasive disease after NAC remains unclear.MethodsData of patients with HER2-positive breast cancer who were treated with HER2-targeted therapy as NAC and completed HP or T-DM1 as adjuvant therapy from October 2018 to October 2022 were retrospectively extracted from the institutional database...The 3-year IDFS and OS of patients with ypT1aN0 were 100% in both groups. The most common adverse events of any grade in the T-DM1 group were aspartate aminotransferase increased (90%) and alanine aminotransferase increased (85%) aminotransferase and platelet count decreased (70%).ConclusionThe 3-year IDFS and OS of patients with ypT1aN0 disease who received HP or T-DM1 as adjuvant therapy were comparable."

Journal • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Ultrasensitive ctDNA Tracking Predicts Exceptional Response in HER2+ Metastatic Breast Cancer (SABCS 2025) - "Most pts in both groups had 1L chemotherapy plus trastuzumab/pertuzumab (82.1% vs 70.8%) and maintenance endocrine tx if ER+ (86.7% vs 62.5%). Here we report, to our knowledge, the first data showing a significant association between MRD detection and duration of response to 1L tx for HER2+ MBC. MRD status at Y1L was highly predictive of exceptional response. Only 2 conventional responders had distant PD without a prior MRD+ sample."

Circulating tumor DNA • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

"longterm" - long-term response (>18 months) in metastatic her2-positive breast cancer: a retrospective analysis of patients diagnosed between 2010 and 2020 in the german bngo network (SABCS 2025) - "All patients received anti-HER2 therapy, most commonly the trastuzumab-pertuzumab combination. Hormone receptor-positive patients often received sequential endocrine therapy. The findings reflect adherence to international guidelines (ASCO, NCCN, AGO) and highlight the role of national networks such as BNGO in generating meaningful real-world oncology data."

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PGR

Long-term outcomes of first-line (1L), guideline-recommended treatment versus alternative regimens in HER2+ metastatic breast cancer (mBC): a retrospective observational study of US electronic health records (SABCS 2025) - "SOC was defined as THP followed by maintenance trastuzumab/pertuzumab after response (with concurrent endocrine therapy for hormone receptor-positive [HR+] disease). Among patients with HER2+ mBC, receipt of guideline-recommended SOC (vs not) in the 1L setting was associated with substantially prolonged long-term outcomes. However, disease characteristics at treatment initiation may have influenced treatment regimen choice and impacted long-term outcomes."

Metastases • Observational data • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Proactive Brain Screening using contrast-enhanced (CE) brain CT scans in HER2+ metastatic Breast Cancer (mBC) (SABCS 2025) - "Brain screening with CT scans is associated with a significantly lower incidence of symptomatic BMs and with a significantly more conserved KPS at BM diagnosis in this retrospective real-world cohort of HER2+ mBC pts treated with pertuzumab-trastuzumab and taxane.These findings support the use of proactive brain imaging for pts with HER2+ mBC. Confirmatory prospective studies are needed to optimize surveillance timing and radiological techniques in this setting."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Radiation Therapy Followed by Intrathecal (IT) Trastuzumab/Pertuzumab in the Management of HER2+ Breast Leptomeningeal Disease: Interim Results from a Phase II Multi-Institutional Study (SABCS 2025) - P1/2 | "The study met its predetermined endpoint for OS to warrant continuing enrollment in the second stage of the phase II trial. Initial trial results are encouraging with study therapy that is well tolerated."

Clinical • P2 data • Breast Cancer • HER-2

Weekly carboplatin and paclitaxel with trastuzumab and pertuzumab (HER2+) or bevacizumab (HER2-) in the neoadjuvant treatment of breast cancer: a phase II trial (SABCS 2025) - "For HER2-negative disease, antiangiogenic therapy with bevacizumab may help improve response rates in certain subsets of breast cancer.Objective: To evaluate the efficacy, safety, and tolerability of an anthracycline-free neoadjuvant regimen of weekly carboplatin and paclitaxel with trastuzumab/pertuzumab (HER2+) or bevacizumab (HER2-). In this single-institution, open-label, phase II trial, patients with histologically confirmed breast cancer (≥1 cm or node-positive) were enrolled. This anthracycline-free neoadjuvant chemotherapy (NAC) regimen demonstrated robust efficacy and favorable tolerability in patients with HER2-positive breast cancer, achieving high long-term progression-free survival (PFS) and response rates, particularly among hormone receptor-negative (HR-) subgroups. In HER2-negative disease, clinical outcomes were more heterogeneous, with particularly promising results observed in patients with TNBC. The 10-year follow-up provided critical insights,..."

Clinical • IO biomarker • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

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 (SABCS 2025) - "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 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."

Clinical • Observational data • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Comparative Analysis of the Effectiveness of Scalp Cooling with PAXMAN Between Dose-Dense AC→PTX and Trastuzumab+Pertuzumab+Docetaxel Regimens in Japanese Breast Cancer Patients (SABCS 2025) - "The overall cohort had a mean age of 49 years. In the ddAC→ddPTX group, 59.5% of patients maintained Grade 1 or lower alopecia at the end of chemotherapy. In the HP+DTX group, 64% achieved Grade 1 or lower alopecia."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Peripheral immune profiling during neoadjuvant HER2-targeted therapy in HER2-positive (HER2+) early breast cancer (EBC): Mass cytometry (CyTOF) analysis from the MARGOT trial (SABCS 2025) - P2 | " The investigator-initiated MARGOT trial (NCT04425018/TBCRC052) randomized 171 patients with stage II-III HER2+ EBC 1:2 to receive neoadjuvant THP (trastuzumab/pertuzumab/paclitaxel) or TMP (margetuximab/pertuzumab/paclitaxel). Neoadjuvant chemotherapy plus anti-HER2 therapy induces early changes in circulating immune populations in HER2+ EBC. PBMC profiling reveals a rapid decline in circulating monocytes and NK cell subsets after 3 weeks of therapy, potentially reflecting tumor migration and contribution to ADCC."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD8

Impact of somatic PIK3CA Mutations on clinical outcomes in HER2-Positive Breast Cancer (SABCS 2025) - "In the recently presented phase 3 Destiny Breast09 trial, the presence of a PIK3CAm was identified as a marker of early progression in HER2+ metastatic BC (mBC) on first line therapy with trastuzumab/pertuzumab monoclonal antibody therapy. We included 212 pts, of which 58 (27.3%) had a documented PIK3CAm. Of the 212, 62 were mBC, of which 15 (26%) had PIK3CAm. The median age at diagnosis was 43."

Clinical • Clinical data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Breast surgery and systemic treatment continuation for patients with de novo metastatic breast cancer and locoregional oligoprogression: a cohort study. (SABCS 2025) - "In the HR+/HER2- subgroup 22/28 (79%) patients were receiving an endocrine therapy-based therapy, in the HER2+ subgroup 19/30 (63%) were on trastuzumab/pertuzumab maintenance. This study suggests that selected patients with de novo mBC and locoregional OPD can benefit from breast surgery while maintaining the same systemic treatment, especially in case of HER2+ disease or a longer a pre-OPD PFS."

Clinical • Metastases • Surgery • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Targeted Axillary Dissection after Neoadjuvant Systemic Chemotherapy in patients with Early Breast Cancer: Estimating the Real-World Impact of Omitted Axillary Lymph Node Dissection using the Canto Cohort (SABCS 2025) - P, P=N/A, P2 | "Adjuvant treatments were: 356 (96.2%) locoregional radiotherapy, 27 (7.3%) chemotherapy, 224 (60.7%) hormonotherapy, 1 (0.3%) immunotherapy, 28 (7.6%) HER2-directed therapy (TDM-1, pertuzumab, trastuzumab)...Kuemmel S. JAMA Surg. 2023 Aug 1; 158(8):807-815"

Clinical • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor