Trastuzumab-based Chemotherapy Research Articles

487P HER2DX ERBB2 mRNA assay following trastuzumab-based chemotherapy in HER2-positive (HER2+) advanced gastric cancer (AGC)

487P HER2DX ERBB2 mRNA assay following trastuzumab-based chemotherapy in HER2-positive (HER2+) advanced gastric cancer (AGC)

Abstract PO2-01-05: Neoadjuvant pyrotinib plus trastuzumab, and chemoterapy in patients with HER2-positive early breast cancer: a real-world study

Abstract Background Pyrotinib is a new oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor that targets human epidermal growth factor receptor 1 (HER1), HER2, and HER4. Previous studies have confirmed it combined with capecitabine is safe and well-tolerated in advanced breast cancer. And also PHEDRA trial had demonstrated the efficacy and safety of pyrotinib combined with trastuzumab and docetaxel neoadjuvant therapy early HER2-positive breast cancer. However, the efficacy of pyrotinib plus trastuzumab-based in real-world neoadjuvant therapy for early breast cancer is unknown. Purpose The present study aimed to explore the efficacy of pyrotinib-based in neoadjuvant therapy for early breast cancer in real-world. Method This is investigator-initiated phase 2 real-world study recruited eligible patients, aged 18–70 years with invasive carcinoma, cT2-3N0-3M0 stage, HER2-positive breast cancer. The patients received 400 mg pyrotinib orally once per day for 21 days and trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) plus different standard chemotherapy, including six 21-day cycles of docetaxel (75 mg/m2) plus carboplatin (6 mg/mL/min), or four cycles of epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) and four cycles paclitaxel (80 mg/m2). The primary endpoint was to calculate the number of patients who achieved a pathological complete response (pCR, ypT0/is, ypN0). (ChiCTR2100052892). Result The results of the 23 patients were reported, The pCR of 12 (52.2%) patients, who reached the threshold for the design, was noted. The study is ongoing. The most frequent grade 3 to 4 adverse events were diarrhea (35.6%), which all the patients received primary prevention of diarrhea, leukopenia (44.8%), and anaemia (23.7%). However, no treatment-related deaths were recorded. Conclusion Previous studies have shown the efficacy and safety of pyrotinib plus trastuzumab and docetaxel in neoadjuvant therapy of HER2-positive early breast cancer. The current trial suggests that pyrotinib plus trastuzumab-based standard chemotherapy in real-world has promising efficacy and manageable toxicity in patients with HER2-positive early breast cancer in a neoadjuvant setting, the trial is ongoing, we will enroll more patients. Citation Format: Jun Zhou, Rui Wang. Neoadjuvant pyrotinib plus trastuzumab, and chemoterapy in patients with HER2-positive early breast cancer: a real-world study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-05.

Successful subtotal gastrectomy and hepatectomy for HER2-positive gastric cancer with liver metastasis after trastuzumab-based chemotherapy: a case report

BackgroundConversion surgery (CS) after chemotherapy is weakly recommended as a promising tool for improving prognoses in patients with unresectable gastric cancer. Moreover, several investigators have demonstrated the clinical efficacy of subtotal gastrectomy (sTG) with a small remnant stomach for the nutritional status and surgical outcome compared with total gastrectomy. Here, we report a patient with liver metastasis from human epidermal growth factor receptor 2 (HER2)-positive gastric cancer who underwent sTG and hepatectomy after trastuzumab-based chemotherapy.Case presentationAn 84-year-old male patient was diagnosed with HER2-positive gastric cancer with a single liver metastasis. He was treated with eight courses of trastuzumab in combination with S-1 and oxaliplatin as first-line chemotherapy. The primary tumor and liver metastasis shrank significantly. The metastatic liver lesion’s reduction rate was 65%. According to the Response Evaluation Criteria in Solid Tumors, the patient had a partial response. Therefore, he underwent an sTG with D2 lymphadenectomy and partial hepatectomy of segment 2. Histopathological examination revealed a grade 3 histological response without lymph node metastases from the primary tumor. No viable cancer cells were observed in the resected liver specimens. The patient received adjuvant chemotherapy with S-1. The postoperative quality of life (QOL) evaluated using the Postgastrectomy Syndrome Assessment Scale-45 was maintained, and the patient was still alive 8 months after the CS without recurrence.ConclusionsAn sTG with a small remnant stomach might be clinically useful for preventing a decline in QOL and improving prognoses in patients with stage IV gastric cancer after chemotherapy.

Two-dimensional speckle tracking echocardiography in chemotherapy-induced cardiotoxicity in females with breast cancer

BackgroundCancer and cardiovascular diseases are the main causes of mortality worldwide. Although the incidence of cancer is rising, modern comprehensive management including surgery, chemotherapy, and radiotherapy led to decreased mortality, but also different cardiovascular complications. Conventional EF measurement fails to detect subtle changes in LV function, so a more sensitive tool is needed.MethodsThe study included 101 asymptomatic female patients with newly diagnosed breast cancer who received anthracycline ± trastuzumab-based chemotherapy regimen. A comprehensive echocardiographic examination was performed before receiving the chemotherapy (T0), at 3 months (T1), and at 6 months after (T2). All patients had pre-treatment normal LV EF. Asymptomatic CTRCD is defined as: severe if new LVEF reduction to < 40%, moderate if new LVEF reduction by ≥ 10 percentage points to an LVEF of 40–49% or new LVEF reduction by, 10 percentage points to an LVEF of 40– 49% and either new relative decline in GLS by .15% from baseline or new rise in cardiac biomarkers and mild if LVEF ≥ 50% and new relative decline in GLS by .15% from baseline and/or new rise in cardiac biomarkers. Symptomatic CTRCD is defined as: very severe if HF requiring inotropic support, mechanical circulatory support, or consideration of transplantation, severe if required hospitalization, moderate if required outpatient intensification of diuretic and HF therapy and mild if there are mild HF symptoms and no intensification of therapy required according to the latest ESC cardio oncology guidelines. The Lower reference value set for RV S’ was less than 10cm/s to define RV systolic dysfunction according to ASE guidelines.ResultsCTRCD occurred in 24 patients (25.5%) while RV systolic dysfunction was more common occurring in 37 patients (39.4%). LV GLS at (T1) (cut-off value < -15% with relative 12.5% reduction from the baseline value) was a strong predictor of CTRCD, but combining LV GLS with RV GLS & RV FWLS was the strongest (AUC = 0.947, sensitivity = 91.67%, specificity = 90%).ConclusionChemotherapy induces biventricular changes with more prevalent deterioration in RV values. Low LV & RV strain values at baseline together with reduction of these values after chemotherapy treatment can predict later CTRCD development. Combining LV GLS with RV GLS & FWLS values at (T1) is the strongest predictor of subsequent CTRCD.

Abstract 17565: Sympathetic Neural Overactivity, Endothelial Dysfunction, Aortic Stiffening, and Diminished Exercise Capacity in Breast Cancer Survivors Treated With Doxorubicin and Trastuzumab-Based Chemotherapy

Introduction: Previous evidence demonstrates that breast cancer (BC) survivors who were treated with doxorubicin and trastuzumab-based chemotherapy have an increased risk of developing cardiovascular (CV) disease at least 7 years after completion of cancer treatment. The reasons for the increased CV disease risk are not completely understood, a constellation of physiological changes may contribute. We hypothesized that BC survivors compared with age- and body mass index (BMI), sex -matched healthy controls, exhibit sympathetic neural overactivity, vascular endothelial dysfunction, aortic stiffening, and diminished exercise capacity. Methods: Twelve women BC survivors, treated with doxorubicin and trastuzumab (age=48±2 years and BMI=28±2 Kg/m 2 ) and fourteen women control subjects (age=46±1 years and BMI=27±1 Kg/m 2 ) were studied. Muscle sympathetic nerve activity (MSNA, Microneurography), endothelium-dependent dilation (brachial artery flow-mediated dilation, BAFMD), aortic stiffness (carotid-femoral pulse wave velocity, CFPWV), blood pressure (BP, Finometer), heart rate (HR, Electrocardiogram), and peak oxygen uptake (V˙O 2 peak, Cardiopulmonary exercise testing) were measured. Results: BC survivors were evaluated 8±2 years after the completion of cancer treatment. Burst frequency and burst incidence of MSNA were higher and BAFMD and V˙O 2 peak were lower in BC survivors than in controls ( p &lt;0.001). There were not differences between the groups in CFPWV, BP, and HR ( p &gt;0.05). MSNA burst frequency and burst incidence were inversely associated with V˙O 2 peak or BAFMD ( p &lt;0.05). Conclusion: Our findings demonstrate that BC survivors have an augmented sympathetic neural activity, endothelial dysfunction, and attenuated exercise capacity, which may help to explain, at least in part, the increased CV risk in this population. Therefore, it is urgent to establish therapeutic strategies (e.g., physical exercise rehabilitation) to restore or alleviate these cardiovascular changes in BC survivors.

Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype

HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making.

TITAN Trial: A Randomized Controlled Trial of a Cardiac Rehabilitation Care Model in Breast Cancer

BackgroundCardiac rehabilitation (CR) modeled care is recommended for patients with breast cancer to mitigate risk of cardiotoxicity. However, the cardiovascular impact of CR-modeled interventions has not been studied. ObjectivesThe purpose of this study was to evaluate if a multidisciplinary model of CR reduces cardiotoxicity and improves cardiovascular risk in patients undergoing breast cancer treatment. MethodsWe randomly assigned patients with stage I to III breast cancer scheduled to receive anthracycline and/or trastuzumab-based chemotherapy to the CR intervention (n = 37) or usual care (n = 37). The intervention included guideline-directed management of cardiovascular risk factors, dietary counselling, and supervised exercise for 52 weeks. Cardiac magnetic resonance imaging, cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, and serum biomarkers were acquired at baseline and 52 weeks. ResultsThere was no difference in the primary outcome, left ventricular ejection fraction (LVEF), between groups at 52 weeks (61% ± 6%). Other markers of cardiotoxicity, including high-sensitivity troponin I and brain natriuretic peptide, were similar between groups. However, total cholesterol (5.2 ± 0.8 mmol/L to 4.7 ± 0.8 mmol/L, P = 0.002) and low-density lipoprotein (3.0 ± 0.7 mmol/L to 2.4 ± 0.7 mmol/L, P < 0.001) decreased in the intervention group at 52 weeks and were unchanged in usual care. In all patients, adverse cardiac and metabolic changes occurred over 52 weeks including reductions in LVEF, left ventricular mass, high-density lipoprotein, lean body mass, insulin-like growth factor-1, as well as increased triglycerides, whole-body and truncal fat mass (all P < 0.050). ConclusionsThe CR-modeled intervention had no effect on LVEF or biomarkers of cardiotoxicity. Future lifestyle intervention trials in patients with breast cancer should consider targeting other risk factors associated with incident cardiovascular disease. (Multidisciplinary Team IntervenTion in CArdio-ONcology [TITAN Study] [TITAN]; NCT01621659)

Pathologic response and survival after neoadjuvant chemotherapy with or without pertuzumab in patients with HER2-positive breast cancer: the Neopearl nationwide collaborative study.

Clinical trials have shown a significant increase in pathologic complete response (pCR) with the addition of pertuzumab to neoadjuvant chemotherapy for patients with early-stage HER-2 positive breast cancer. To date, limited studies have examined comparative outcomes of neoadjuvant pertuzumab in real-world setting. The Neopearl study aimed to assess comparative real-life efficacy and safety of neoadjuvant pertuzumab for these patients. We conducted a nationwide retrospective analysis involving 17 oncology facilities with a certified multidisciplinary breast cancer treatment committee. We identified patients with HER-2 positive stage II-III breast cancer treated with neoadjuvant chemotherapy based on trastuzumab and taxanes with or without pertuzumab. All patients underwent breast surgery and received a comprehensive cardiologic evaluation at baseline and after neoadjuvant treatment. Patients who received the combination of pertuzumab, trastuzumab, and chemotherapy constituted case cohort (PTCT), whereas those treated with trastuzumab and chemotherapy accounted for control cohort (TCT). The pCR rate and 5-year event free survival (EFS) were the primary outcomes. Secondary end-points were rates of conversion from planned modified radical mastectomy (MRM) to breast conservation surgery (BCS) and cardiotoxicities. From March 2014 to April 2021, we included 271 patients, 134 (49%) and 137 (51%) in TCT and PTCT cohort, respectively. Positive axillary lymph nodes and stage III were more frequent in PTCT cohort. The pCR rate was significantly increased in patients who received pertuzumab (49% vs 62%; OR 1.74, 95%CI 1.04-2.89) and with HER-2 enriched subtypes (16% vs 85%; OR 2.94, 95%CI 1.60-5.41). After a median follow-up of 5 years, the 5-year EFS was significantly prolonged only in patients treated with pertuzumab (81% vs 93%; HR 2.22, 95%CI 1.03-4.79). The same analysis performed on propensity score matched population showed concordant results. On univariate analysis, only patients with positive lymph nodes were found to benefit from pertuzumab for both pCR and 5-year EFS. The rates of conversion from MRM to BCS and cardiologic toxicities did not differ between the cohorts. Our findings support previous data on improved outcomes with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy. This benefit seems to be more significant in patients with clinically positive lymph nodes.

126MO HER2DX and pathological complete response in HER2-positive breast cancer: A combined analysis of 4 neoadjuvant studies

The optimal neoadjuvant therapy for HER2-positive breast cancer patients is subject to ongoing debate and the use of biomarkers can help to personalise treatment decision. The 27-gene HER2DX test predicts pathological complete response (pCR) following neoadjuvant trastuzumab-based chemotherapy. Here, we evaluated the value of HER2DX to predict increases in pCR rate when 1) a second anti-HER2 agent is added to trastuzumab and chemotherapy, and 2) multi-agent chemotherapy is used instead of a single agent taxane in the context of dual HER2 blockade. We conducted a combined analysis of four neoadjuvant cohorts with HER2DX and clinical data (i.e., DAPHNe, GOM-HGUGM-2018-05, CALGB-40601 and ISPY-2). All patients were treated with neoadjuvant trastuzumab (n=568) in combination with multi-agent chemotherapy (n=282), a single taxane (n=286), pertuzumab (n=264), lapatinib (n=103) or without a second anti-HER2 drug (n=201). Interaction tests were performed to evaluate the predictive capacity of HER2DX to identify patients who benefit most from each treatment approach. HER2DX pCR as continuous score was significantly associated with pCR in all patients (odds-ratio [OR]=1.62, 95% CI 1.43-1.85; AUC=0.75), in patients treated with trastuzumab and chemotherapy (OR=1.48, 1.18-1.86) and in patients treated with dual HER2 blockade and chemotherapy (OR=1.69, 1.50-1.91). A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR=4.10, 1.85-9.07; interaction test p=0.03). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR=2.52, 1.18-5.52; interaction test p=0.01). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of type of treatment. HER2DX might help identify patients with HER2-positive breast cancer who benefit from neoadjuvant dual HER2 blockade in combination with a single taxane.

Outcomes of the patients with metastatic male breast cancer.

The goal of this research is to investigate the clinical characteristics and prognosis of men with metastatic breast cancer (mMBC). A retrospective analysis of the data of 28 patients was conducted. Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS) and prognostic variables. At the time of diagnosis, the median age was 57 years (range 26-86). The most prevalent pathological subtype was invasive ductal carcinoma (92.6%). HER2 positivity was 21.6% in patients, with estrogen and progesterone receptor positivity at 96.4% and 71.4%, respectively. Bone-75%, lung-39.3%, brain-21.4%, and adrenal gland-10.7% were the most prevalent metastatic sites. Trastuzumab-based chemotherapy was given to six patients. During the study period, 14 patients (or half) died. All patients had a median OS of 42.6 months (range: 21.6-63.7). The OS rates after 1, 3, and 5 years were 95.7%, 54.2%, and 36.6%, respectively. The number of metastatic locations (P = 0.045), brain metastasis (P = 0.033), and a history of regular alcohol intake (P = 0.008) were all shown to be statistically significant factors affecting OS in univariate analysis. However, multivariate analysis did not support the findings. In addition, we discovered that trastuzumab-based therapy and de-novo metastatic disease had no effect on OS for mMBC. The data on mMBC is restricted because of its rarity. The prognosis of mMBC was shown to be poor in this investigation. Despite the small number of patients, we discovered that in univariate analysis, having brain metastases, the number of metastatic locations, and a history of alcohol intake may be prognostic factors.

Abstract P1-13-15: Elevated TCEAL9 Expression Is Correlated With Trastuzumab-based Neoadjuvant Chemotherapy Resistance In HER2-positive Breast Cancer

Abstract Background: -Trastuzumab-based neoadjuvant chemotherapy has shown to have remarkable clinical benefits for HER2-positive breast cancer patients who had higher tumor burden. -Patients who achieved pathological complete response (pCR) are known to have better prognosis. -However, certain patients have little response or are not sensitive to trastuzumab-based treatment regimens. -Understanding the mechanism of trastuzumab resistance is crucial for the development of new therapeutic strategy. Objectives: To investigate the role of TCEAL9 in developing trastuzumab resistance in HER2-positive breast cancer Methods: A total of 83 patients who received paclitaxel, carboplatin and trastuzumab neoadjuvant chemotherapy in Fudan University Shanghai Cancer Center(FUSCC) from 2016 to 2018 were enrolled in this study. After completed neoadjuvant chemotherapy and surgery, gene expressions were compared between the pCR and non-pCR groups. Total RNA from formalin-fixed paraffin-embedded tissue sections was isolated and RNA-sequencing was performed. Gene sets from GEO dataset GSE52707 were used to analyze TCEAL9 expression in resistant and non-resistant cell lines. Gene expression levels were converted into log2 values and row-wised standardized. BT-474 and SK-BR-3 cell lines were transduced with each expression lentivirus, followed by selection with puromycin for stable expression. TCEAL9 mRNA and protein level evaluation was evaluated by qPCR and western blot. The influence of TCEAL9 expression on proliferation and sensitivity to HER2-targeted therapy was evaluated by CCK8. BT-474 and SK-BR-3 transfected cells were plated in 96-well plates with 4,000 cells per well. After 3 or 5 days of incubation with trastuzumab, pertuzumab or lapatinib, the viability of cells was measured using Cell Proliferation Assay. Comparisons between Kaplan-Meier curves were performed using the long-rank test. Results: TCEAL9 was elevated significantly (P&amp;lt; 0.05) in non-pCR patients in the FUSCC cohort and was associated with lapatinib resistance in GSE52707 from GEO datasets. Patients with elevated TCEAL9 expression had worse recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and progression-free survival (PPS) (all P&amp;lt; 0.05)by using KM-plotter. Overexpression of TCEAL9 was associated with lapatinib(IC50= 5.56 vs 10.90nM) and trastuzumab + pertuzumab(IC50= 745 vs 635nM) resistance in BT-474 and SK-BR-3 respectively, but has no influence in proliferation. In this study, we found that TCEAL9 could induce HER2-positive breast cancer cells resistance to HER2-targeted therapy through the activation of mTOR signaling pathway. After EGFR stimulation, TCEAL9 has a higher mTOR phosphorylation level in BT-474 cells. TCEAL9 elevation also increased HER2 and mTOR phosphorylation after lapatinib treatment in SK-BR-3 cells. In addition, the elevation of TCEAL9 has a positive correlation with HER2 signaling pathways such as EGFR, PIK3R1, FOXO1 and AKT3 in TCGA datasets. Conclusions: TCEAL9 expression correlates with trastuzumab resistance and high TCEAL9 expression is associated with poor prognosis in HER2-positive breast cancer patients. Citation Format: Chih Wan Goh, Wei-Ru Chi, Liyi Zhang, Qi Zhang, Ming Chen, Min Xiong, Douwaner Liu, Hengyu Ren, Bingqiu Xiu, Jingyan Xue, Yayun Chi, Jiong Wu. Elevated TCEAL9 Expression Is Correlated With Trastuzumab-based Neoadjuvant Chemotherapy Resistance In HER2-positive Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-13-15.

Abstract P4-01-27: Prognosis and treatment landscape of HER2-positive metastatic breast cancer (MBC) before the availability of tucatinib and trastuzumab-deruxtecan: Results from the Austrian AGMT_MBC-Registry

Abstract Background: New anti-HER2 drugs such as tucatinib and trastuzumab deruxtecan (T-DXd) have shown to improve survival of HER2+ MBC in clinical phase III trials. To allow a future confirmation of this survival advantage in real world, we evaluated the prognosis of HER2+ MBC patients before the availability of tucatinib and T-DXd in Austria. Furthermore, we analyzed the treatment landscape and the drop-out rate between subsequent lines of therapy as documented in the MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT). Patients and methods: The AGMT-MBC-Registry is a multicenter nationwide ongoing retrospective and prospective registry for MBC patients in Austria. In this analysis, patients with known HER2 status, available survival data, at least one treatment line and diagnosis of metastatic disease after 01/04/2013 (pertuzumab available) were included. Follow-up was censored at Dec 31, 2020, when tucatinib und T-DXd became available. Results: As of 04/05/2022, 2,235 patients have been included in the registry. Out of 2,000 evaluable patients, 362 (18.1%) were HER2+, of which 171 (47.2%) fulfilled the inclusion criteria. Out of them 69.0% were hormone-receptor positive. In patients with metachronous metastatic disease (53.2%), 61.5% had received trastuzumab-based treatment for early breast cancer. Median overall survival (OS) for all patients was 50.1 months (95%CI 40.7-73.0), and 66.1 months (95%CI 50.1-NA) for those who received a pertuzumab combination as first-line treatment. The drop-out rate from 1st- to 5th-line was 26.9%, 24.4%, 28.3% and 36.7%, respectively. This yields an estimated percentage of patients that received at least 3, 4, and 5 treatment lines for advanced disease of 55.2%, 39.6% and 25.1%, respectively. In first line, 50.9% received trastuzumab plus pertuzumab and 11.1% T- DM1. In second line, 38.9% were treated with T-DM1 and 35.6% with trastuzumab-based chemotherapy or endocrine therapy. In third line, 11.3%, 17.0% and 49.1% received T-DM1, lapatinib-based and trastuzumab-based therapy, respectively. Outcomes according to treatment line are shown in Table 1. Conclusion: Median overall survival of HER2+ MBC in Austria who received a pertuzumab combination treatment is comparable to the results reported in the registration CLEOPATRA trial. In this analysis, only ~40% of patients are estimated to receive more than three treatment lines and treatment benefit diminished from line to line. This underlines the importance of investigating and ultimately using the most effective compounds in early treatment lines in order to allow more patients to benefit from these life prolonging drugs. Table 1: Outcome according to treatment line Citation Format: Simon P. Gampenrieder, Gabriel Rinnerthaler, Christoph Tinchon, Andreas Petzer, Marija Balic, Sonja Heibl, Margit Sandholzer, August F. Zabernigg, Daniel Egle, Christopher Hager, Petra Pichler, Florian Roitner, Johannes Andel, Kathrin Strasser-Weippl, Michael Knauer, Michael Hubalek, Christian F. Singer, Richard Greil. Prognosis and treatment landscape of HER2-positive metastatic breast cancer (MBC) before the availability of tucatinib and trastuzumab-deruxtecan: Results from the Austrian AGMT_MBC-Registry [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-27.

Abstract P2-01-07: Combination of pyrotinib with trastuzumab, taxanes and platinum as neoadjuvant therapy in patients with HER2-positive early or locally advanced breast cancer: a multicenter phase II trial

Abstract Background: Pyrotinib (an irreversible pan-ErbB inhibitor) plus capecitabine have shown clinically and statistically meaningful progression-free survival and overall survival benefits with acceptable tolerability in patients with HER2-positive metastatic breast cancer in phase 3 trials. In this study, we assessed the efficacy and safety of neoadjuvant pyrotinib plus trastuzumab, taxanes and platinum in women with HER2-positive early or locally advanced breast cancer. Methods: In this multicenter, single-arm, phase II trial (ChiCTR2000039286), treatment-naive patients with early or locally advanced (T2-3, N0-3, M0) breast cancer received pyrotinib 400 mg once daily, plus trastuzumab (8 mg/kg loading dose and 6 mg/kg maintenance dose), docetaxel (75 mg/m2) or nab-paclitaxel (125 mg/m2), and carboplatin (AUC=5-7) on day 1 of each 21-day cycle for 6 cycles before surgery. All patients also received 1-year adjuvant pyrotinib combined with trastuzumab after surgery. The primary endpoint of the study was total pathological complete response (tpCR, ypT0/is ypN0) rate. The secondary endpoints were breast pathological complete response (bpCR) rate, objective response rate, adverse events (AEs) and invasive disease-free survival. Results: Between October 2020 and March 2022, a total of 35 patients were enrolled from 7 sites. By the data cut-off date on June 29, 2022, two patients withdrew from the study, and one received other anti-tumor therapies. Thirty-two patients received neoadjuvant therapy and surgery (modified intention-to-treat [mITT] population), and 30 of whom completed the 6-cycle neoadjuvant therapy (per-protocol [PP] population). The local pathologist-assessed tpCR rate was 59.4% (19/32) and 60.0% (18/30) in the mITT and PP populations, and bpCR rate was 65.6% (21/32) and 66.7% (20/30) in the mITT and PP populations, respectively. The tpCR rate was 68.8% (11/16) among patients with hormone receptor-negative disease and 50.0% (8/16) among those with hormone receptor-positive disease in the mITT population. Of 30 patients with preoperative imaging assessments, 26 (86.7%) achieved an objective response. Treatment-related AEs (TRAEs) were reported in 34 (97.1%) of 35 patients, with the most common being diarrhea (82.9%) and platelet decreased (48.6%). The most common grade ≥3 TRAEs were diarrhea (25.7%), platelet decreased (8.6%), neutropenia (8.6%), vomiting (5.7%), and alanine aminotransferase increased (5.7%). No grade 4 or 5 diarrhea events occurred. Conclusions: This study showed similar efficacy with previous reports, neoadjuvant pyrotinib plus trastuzumab-based chemotherapy exhibits promising efficacy and manageable toxicity in patients with HER2-positive early or locally advanced breast cancer. Citation Format: Hao Zhou, Lei Wang, Lei Wang, Zhaoji Guo. Combination of pyrotinib with trastuzumab, taxanes and platinum as neoadjuvant therapy in patients with HER2-positive early or locally advanced breast cancer: a multicenter phase II trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-01-07.

Abstract OT2-08-02: SOLTI-1907 ATREZZO: Targeting hormonal receptor negative (HR-) or PAM50 non-luminal disease with atezolizumab in combination with trastuzumab and vinorelbine in HER2-positive metastatic breast cancer (MBC)

Abstract Background Today, there is no clear therapeutic algorithm for patients with metastatic HER2-positive (HER2+) breast cancer (BC) who have progressed to trastuzumab, pertuzumab, tyrosine kinase inhibitors and antibody-drug conjugates (ADC). Among the emerging strategies, the use of immune checkpoint inhibitors in combination therapy is showing promising clinical benefit in the advanced setting of HER2+ BC by overcoming immune resistance and enhancing antitumor cellular immunity. The intrinsic subtypes Basal-like and HER2-enriched (i.e PAM50 non-luminal tumors) represent approximately the 60% of HER2+ BC and are associated with higher expression of immune-related genes, tumor-infiltrating lymphocytes (TILs) presence and high tumor mutational burden (TMB), compared to luminal subtypes. Additionally, immune infiltration and TMB in HER2+ BC are associated with chemo/antiHER2 responsiveness and with potential benefit from anti-PD-1/PD-L1 inhibitors. We hypothesize that combining atezolizumab with trastuzumab and vinorelbine may improve outcomes in HR- or PAM50 non-luminal/HR-positive (HR+) disease within HER2+ MBC. Methods ATREZZO is an open-label, single-arm, Simon 2-stage, multicenter phase II study. The trial will include 55 pre- or post-menopausal female or male patients with unresectable locally advanced or metastatic HR- or PAM50 non-luminal/HR+ HER2+ BC and progressed to trastuzumab-based chemotherapy and anti-HER2 ADC. Prior pertuzumab is allowed, but not required. Treatment consists of atezolizumab IV 1200 mg every 3 weeks combined with trastuzumab and vinorelbine. Patients with stable, progressing, or untreated brain metastasis not requiring immediate local therapy are eligible. The primary objective is to evaluate the Overall Response Rate (ORR) according to RECIST v 1.1 and secondary endpoints include ORR in patients with PD-L1 positive breast cancer, clinical benefit rate, overall survival and progression-free survival. The final recruited population will contain no more than 60 % of patients with PD-L1 negative tumors. Tumor assessments will be performed every 9 weeks. Incidence, duration and severity of adverse events, and further correlative molecular analyses will be also evaluated. An interim analysis will be conducted when 19 patients are evaluable for ORR and if the number of responses is ≥ 3, 36 additional patients will be included. As of July 15th, 2022, 48 patients were screened and 15 were included in sixteen Spanish sites. This study was funded by Roche Farma SA. Trial identification: NCT04759248 Citation Format: Eva Ciruelos, Antonia Perelló, Santiago González-Santiago, Ana López, Francisco Javier Salvador Bofill, Cinta Albacar, Juan Miguel Cejalvo, Santiago Escrivá-de-Romani, Isabel Blancas, Sonia Pernas, Olga Martínez-Sáez, Josefina Cruz, Jose Ponce, Sonia Servitja, Maria-Eva Perez-Lopez, Juan A Guerra, Esther Sanfeliu, Cesar A Rodríguez, Guillermo Villacampa, Lorea Villanueva, Pablo Tolosa, Tomás Pascual, Aleix Prat. SOLTI-1907 ATREZZO: Targeting hormonal receptor negative (HR-) or PAM50 non-luminal disease with atezolizumab in combination with trastuzumab and vinorelbine in HER2-positive metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-08-02.

Absolute Lymphocyte Count Changes During Neoadjuvant Chemotherapy are Associated With Prognosis of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Patients

ntroduction/BackgroundSome reports have shown that absolute lymphocyte count (ALC) is associated with prognosis in breast cancer; however, the impact of ALC changes remains unclear. This study aimed to investigate the relationship between ALC changes during neoadjuvant chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients and disease prognosis. Patients and MethodsThis retrospective cohort study January 2010 to September 2020) included patients diagnosed with HER2-positive breast cancer and treated with trastuzumab-based neoadjuvant chemotherapy. The ALC ratio was defined as the ALC value after administration of the anti-HER2 drug divided by the ALC value before administration. The optimal ALC ratio cut-off value was identified using the receiver operating characteristic curve analysis and Youden's index. The relationship between the ALC ratio and disease-free survival was assessed using the Kaplan–Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. ResultsData from a total of 100 HER2-positive breast cancer patients were analyzed. The cut-off value of the ALC ratio was set as 1.142. The median follow-up period was 52.0 (range: 5.1-123.7) months. The 5-year disease-free survival rates were 88.4% and 60.9% in the high-and low-ALC ratio groups, respectively, and were significantly higher in the high-ALC ratio group (p = .0031). The ALC ratio was an independent prognostic factor in multivariate Cox proportional hazards analysis (p = .0032). ConclusionHER2-positive breast cancer patients with a higher ALC ratio during trastuzumab-based neoadjuvant chemotherapy may have a better prognosis than their counterparts.

Evaluation of Prognostic Factors and Trastuzumab-based Treatments in HER2/Neu-positive Metastatic Gastric Cancer.

To determine the efficacy of trastuzumab-based treatment in patients with HER2/neu-positive metastatic gastric cancer. Observational study. Department of Medical Oncology, Istanbul University, Institute of Oncology, Istanbul, Turkey, between January 2014 and December 2020. The clinicopathological characteristic and treatment data of patients with HER2/neu-positive metastatic gastric cancer were recorded retrospectively. Kaplan-Meier analysis was performed to compare the chemotherapy regimens. Sixty-three patients were included in the study. The average age was 61. Female patients accounted for 27% of the total, while male patients accounted for 73%. De novo metastatic cases accounted for 44 (69.8%) of the total number of patients. The median survival time was 13.6 (8-19.3) months. Complete response was 6.3%, partial response was 39.7%, and the stable response was 9.5% with trastuzumab-based chemotherapy. The overall survival (p= 0.45) and progression-free survival (p=0.893) were similar for different chemotherapy regimens. The grade 1-2 to grade 3-4 toxicity ratio was 79.6% and 20.6%, respectively. The patients' performance (p<0.001) and the number of metastatic sites (p=0.001) were both shown to be unfavourable predictive variables for OS in multivariate analysis. The addition of taxane to trastuzumab-based combinations (with platinum and fluoropyrimidine) did not affect overall and progression-free survival in this research. Three or more metastatic sites and poor performance status were found as the unfavourable prognostic variables for overall survival. Gastric cancer, Trastuzumab, Chemotherapy, Prognostic factors.

Efficacy of neoadjuvant treatment with or without pertuzumab in patients with stage II and III HER2-positive breast cancer: a nationwide cohort analysis of pathologic response and 5-year survival

BackgroundPathologic complete response (pCR) rates in early stage HER2-positive breast cancer improved after pertuzumab was added to neoadjuvant treatment. However, survival benefit is less-well established and seems mostly limited to node-positive patients. We used national cancer registry data to compare outcomes of patients treated with and without pertuzumab. MethodsWe identified stage II-III HER2-positive breast cancer patients treated with neoadjuvant trastuzumab-based chemotherapy between November 2013 until January 2016 from the Netherlands Cancer Registry. During that period pertuzumab was only available in the 37 hospitals that participated in the TRAIN-2 study. Missing grade and pCR-status were obtained from the Dutch Pathology Registry (PALGA) and cause of death from Statistics Netherlands. We used multiple imputation to impute missing data, multivariable logistic regression to evaluate the association between pertuzumab and pCR (ypT0/is, ypN0) and multivariable Cox regression models for overall survival and breast cancer specific survival (BCSS). ResultsWe identified 1124 patients of whom 453 received pertuzumab. Baseline characteristics were comparable, although tumor grade was missing more often in patients treated without pertuzumab (12% vs. 2%). Pertuzumab improved pCR rates (41% vs 65%, adjusted odds ratio [aOR] 2.91; 95% CI:2.20–3.94). After a median follow-up of 6.0 years, 5-year BCSS rates were 95% and 98% respectively (adjusted hazard ratio [aHR]: 0.58; 95% CI:0.36–0.95). Younger patients derived more benefit from pertuzumab, but no other significant interactions were found. ConclusionThese results support earlier data of a small survival benefit with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy which is most meaningful in younger patients.

Outcomes and prognostic factors in patients with HER2-positive metastatic breast cancer with brain metastasis.

e14002 Background: Breast cancer is the most common malignancy in females. Brain metastasis is a poor prognostic factor in breast cancer. Brain metastasis can develop in about half of the HER2- positive metastatic breast cancer patients. The study was aimed to determine outcomes and prognostic factors in HER2 positive metastatic breast cancer patients who had brain metastasis. Methods: We evaluated the HER2-positive metastatic breast cancer patients with brain metastasis between 2008 and 2018. Data of the patients were recorded retrospectively. Kaplan Meier and Cox regression analysis were used for survival analysis and prognostic factors. Results: Eighty-three patients were included in the study. The median age was 49 (range, 25-76). Thirty-two (38.6%) patients had de-novo metastatic disease at diagnosis. The most common histopathological type was invasive ductal carcinoma (88.4%). The estrogen receptor and progesterone receptor positivity ratios were 42.2% and 28.9%, respectively. At the beginning of brain metastasis, the median number of extra-cranial metastasis was 2 (range, 0-4). The most common extra-cranial metastasis sites were bone (63.9%), liver (41%), and lung (34.9%), respectively. Twenty-eight patients (41.8%) had solitary brain metastasis. The median size of brain metastasis was 16 mm (range, 5-63) at diagnosis. All patients had treated with trastuzumab-based chemotherapy, 29 patients (34.9%) TDM-1, and 73 patients (88%) lapatinib+capesitabine combination. Seventeen patients (20.5%) had undergone craniotomy, and 82 patients (98.8%) received brain radiotherapy. The patients also received hormonotherapy (41%) and bisphosphonates (56.6%). At a median follow-up of 36 months (range 5.9-177.7) from beginning metastasis, the median overall survival was 34.9 months (95% CI, range 24.6-45.2). In multivariate analysis, age at diagnosis (p = 0.005), presence of five and over brain metastasis (p = 0.016), the number of chemotherapy used with trastuzumab (p = 0.017), and receiving three different HER2-targetted therapy (p = 0.032) were statistically significant for overall survival. However, size of brain metastasis (p = 0.091), lung metastasis (p = 0.428), liver metastasis (p = 0.338), bone metastasis (p = 0.132), and hormone positivity of tumor (p = 0.238) were not. Conclusions: Real-life outcomes of HER2-positive breast cancer patients with brain metastases were presented in this study. We showed that age at diagnosis, number of brain metastasis, number of chemotherapy received with trastuzumab, and had received three different HER2 targetted therapy was prognostic factors for overall survival.

Prognostic factors influencing progression-free survival in HER2 positive metastatic breast cancer patients who treated with lapatinib and capecitabine combination.

e13031 Background: Her2 positivity is detected in about 20% of breast cancer patients. After trastuzumab-based therapy, lapatinib and capecitabine combination is a treatment option in HER2-positive metastatic patients. The study aimed to evaluate the prognostic factors in HER2 positive metastatic breast cancer patients treated lapatinib and capecitabine combination. Methods: We evaluated data of the HER2 positive metastatic breast cancer patients who were treated with lapatinib and capecitabine retrospectively. The patients' clinical, pathological, and treatment features were recorded from the hospital database. Kaplan Meier and Cox regression analysis were used for survival analysis. Results: 102 patients were included in the study. The median age was 47 (range, 24-87), and 99 (97.1%) patients were female. The number of de-novo metastatic patients was 44 (43.1%). The most common metastatic sites were bone (62.4%), brain (58.6%), liver (35.6%), and lung (34.7%), respectively. All patients were previously treated with trastuzumab-based chemotherapy. 44 (44.1%) patients received hormonotherapy (tamoxifen or aromatase inhibitor), and 23 (22.5%) patients palliative radiotherapy. Complete response was 8.2%, partial response 32%, and stable disease 25.8% with lapatinib and capecitabine combinations. At a median follow of 11.6 months, progression-free survival was 8 (95% CI, 5.1-10.8) months. In multivariate analysis, age (p = 0.020), de-novo metastatic disease (p = 0.028), and endocrine therapy (p = 0.020) were statistically significant prognostic factors for progression-free survival. However, history of breast surgery (p = 0.060), number of chemotherapy used with trastuzumab (p = 0.338), number of metastatic sites (p = 0.257), and palliative radiotherapy (p = 0.394) were not significant. Conclusions: We showed real-life outcomes of the lapatinib and capecitabine combination in metastatic HER2-positive breast cancer patients. Also, we detect that being under age 50 years, de-novo metastatic disease, and hormone-negative tumor were poor prognostic factors of progression-free survival.

A prognostic scoring system for conversion surgery after trastuzumab-based chemotherapy for human epidermal growth factor receptor 2-positive advanced gastric cancer

PurposeTo investigate the clinical indications and prognostic significance of surgical interventions after chemotherapy using trastuzumab-containing regimens for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC).MethodsA total of 146 patients with AGC who underwent chemotherapy were enrolled in this retrospective study. Tumors with an immunohistochemistry (IHC) score of 3 + or an IHC score of 2 + plus fluorescence in situ hybridization positivity were defined as HER2-positive AGC. We devised a scoring system for predicting prognosis associated with conversion surgery.ResultsThirty-three patients received trastuzumab-based chemotherapy for HER2-positive tumors. Multivariate analyses identified advanced age, peritoneal dissemination, histologically undifferentiated tumors, and tumor response of progressive disease as independent prognostic factors for a worse prognosis. Twelve patients with HER2-positive AGC underwent conversion surgery. The conversion surgery group of patients with HER2-positive AGC had a better prognosis than the chemotherapy-alone group. A prognostic scoring system based on age, peritoneal dissemination, and histological type was significantly correlated with the presence or absence of conversion surgery and the prognosis of patients with HER2-positive AGC.ConclusionsOur scoring system has the clinical potential to predict prognosis associated with conversion surgery after trastuzumab-containing chemotherapy for patients with HER2-positive AGC.