A national real-world prospective study to assess the effectiveness of adjuvant trastuzumab-dkst in HER2 breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13023-e13023
Author(s):  
Leandro Ladislau Alves ◽  
Lara Lopes Facó ◽  
Ana Carolina Cardoso ◽  
Alexandre Alcantara ◽  
Augusto Theodoro Figueiredo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Real World ◽  
Invasive Disease ◽  
Disease Relapse ◽  
Relapse Free Survival ◽  
Her2 Positive ◽  
Curative Intent ◽  
Free Survival ◽  
Her2 Breast Cancer

e13023 Background: Real-World Evidence (RWE) are gain importance once they are designed to evaluate the effectiveness of drugs whose efficacy has already been demonstrated in randomized controlled trials. In 2017, Brazil approved the first biosimilar of trastuzumab for treatment of breast cancer (BC) with overexpression of HER2. The anti-HER2 treatment significantly improves outcome in patients with HER2-positive BC. Trastuzumab-dkst is clinically effective biosimilar and help to increase access to BC treatment. The aim of this RWE is to address the effectiveness of adjuvant biosimilar trastuzumab-dkst in Brazilian women with early HER2+ BC. Methods: This is a national, multicenter, observational, prospective, RWE study conducted in Brazilian institutions. A hundred and seventy female adult patients, with diagnosis of early stage HER2-positive BC, who received at least one dose of trastuzumab-dkst as adjuvant therapy will be included. The follow-up period will be 5 years after the first dose of trastuzumab-dkst, unless tumor recurrence or death. The safety endpoints are the occurrence adverse events. The effectiveness endpoints are invasive disease relapse-free survival rate at 18, 24, 30 and 36 months after the start of biosimilar use, the invasive disease relapse-free survival after curative-intent surgery and overall survival after curative intent surgery. Given the inexistence of a specific hypothesis to be tested, sample size was based on the accuracy of the two-sided 95% confidence interval (95% CI) for the invasive disease relapse-free survival rate. Results: The recruitment planning covered 21 sites across the five regions of Brazil: North, Northeast, Midwest, Southeast, and South. From those 21 sites, 14 ( > 50%) have already been approved by their local ethical committee for patient recruitment. At 7 months, we have enrolled 50 patients over the five Brazilian regions, which means 29.4% of the total. Conclusions: To conduct RWE in Brazil is still challenging and we have listed 5 possible reasons: (1) there are few RWE studies running in the country, (2) we do not have trialists experienced in RWE design; (3) low medical commitment to adverse event report in RWE; (4) low budget for RWE; (5) slow ethics and regulatory process approval in Brazil. Considering the pioneering and challenges to develop the RWE in Brazil, we are achieving optimum adherence from medical sites. Moreover, roughly one quarter of the target recruitment was reached in the first 7 months after the study start date. Clinical trial information: NCT03892655 .

scholarly journals Real-world data of subcutaneous trastuzumab and intravenous pertuzumab as neoadjuvant therapy for localized HER2+ breast cancer in Panama

2021 ◽  
pp. BMT
Author(s):  
Franklin Castillero Rodriguez ◽  
Omar Castillo-Fernandez ◽  
Maria Lim-Law ◽  
Cristiane Martin Palacios ◽  
Lilian Montano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Real World ◽  
Complete Response ◽  
Her2 Overexpression ◽  
Relapse Free Survival ◽  
Real World Data ◽  
Free Survival ◽  
Her2 Breast Cancer ◽  
Study Results

The aim of this study is to determine the effectiveness of subcutaneous trastuzumab in combination with intravenous pertuzumab and chemotherapy for patients with HER2-overexpressing localized breast cancer treated in our center. Methods: This was a descriptive, retrospective, real-world study. Results: Of 156 patients, pathological complete response (pCR) was achieved in 64.1%. A multivariate analysis showed a relationship with a negative hormone receptor (HR) expression and a HER2 score of 3+ by immunohistochemistry. Relapse-free survival (RFS) was higher in patients with pCR. Conclusion: Neoadjuvant therapy with dual blockade using intravenous pertuzumab and subcutaneous trastuzumab for HER2+ localized breast cancer in routine clinical practice resulted in a 64.1% pCR rate. Additionally, this outcome was related to a negative HR expression and HER2 overexpression, and correlated with higher relapse-free survival.

scholarly journals Adding pertuzumab to adjuvant therapy for high-risk HER2-positive early breast cancer in APHINITY: a GRADE analysis

2020 ◽  
Vol 9 (6) ◽  
pp. 423-430 ◽  
Author(s):  
Alberto Zambelli ◽  
Giovanni Pappagallo ◽  
Paolo Marchetti
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Free Survival ◽  
Distant Relapse ◽  
Disease Free

Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population.

Correlation of quantitative p95HER2, HER2, and HER3 protein expression with pathologic complete response (pCR) in HER2-positive breast cancer patients (pts) treated with neoadjuvant chemotherapy and trastuzumab.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 137-137 ◽  
Author(s):  
Jose Caetano Villasboas ◽  
Judith Hurley ◽  
Jodi Marie Weidler ◽  
Agnes Paquet ◽  
Carmen Gomez Fernandez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Metastatic Breast ◽  
Complete Response ◽  
Invasive Disease ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Additional Information ◽  
Her2 Breast Cancer ◽  
Poor Outcomes

137 Background: Elevated p95HER2 [HER2-M611-CTF (carboxy-terminal-fragment) also known as p95] expression has been correlated with poor outcomes in HER2+ pts with metastatic breast cancer treated with trastuzumab (T); however, limited data is available on the correlation between p95 and pCR to T in the neoadjuvant (NEO) setting, where p95 was measured by immunohistochemistry. The current study aims to determine whether quantitative p95, HER3 and HER2 expression correlated with pCR in pts treated with T + chemotherapy in the NEO setting. Methods: pCR data and quantitative HER2 (H2T), p95, and HER3 (H3T) results by HERmark/VeraTag assays were available in 45 patient cases with pre-therapy, formalin-fixed, paraffin-embedded breast tumors. pCR was defined as the absence of invasive disease in the breast. Quantitative biomarker data were correlated with pCR according to previously published or presented biomarker cutoffs. Results: The overall pCR rate was 46.7% (ER+: 14.3% vs. ER-: 75%; p<0.0001) and was significantly associated with higher H2T levels (p=0.02) and lower H3T levels (p=0.04). In ER- subjects (N=24), no difference in H2T levels was observed between pCR vs non-pCR groups (median H2T=111.5 vs 150.5, respectively; p=0.721). However, within the ER+ group (N=21), H2T levels were significantly higher in the pCR group vs non-pCR group (median H2T=254 vs 37.3; p=0.024). Using multivariate logistic regression, increasing log(H2T) (p = 0.012), ER-negativity (p = 0.027) and low p95 (p = 0.074) were found to correlate or trend with pCR. Conclusions: pCR was significantly associated with high H2T, particularly in ER+ HER2+ breast cancer pts who received NEO therapy with T + chemotherapy. Lower H3T was also associated with pCR. A trend towards pCR was seen in tumors with low p95. These data suggest that quantitative H2T, H3T and p95 may provide additional information on response to T-based regimens in breast cancer stratified by ER status. Additional investigation into the relationship between quantitative H2T, p95 and H3T expression and T response in the NEO setting in larger cohorts is warranted.

Impact of delaying initiation of adjuvant chemotherapy in breast cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1022-1022
Author(s):  
Debora De Melo Gagliato ◽  
Ana M. Gonzalez-Angulo ◽  
Xiudong Lei ◽  
Sharon Hermes Giordano ◽  
Richard L. Theriault ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Survival Outcomes ◽  
Relapse Free Survival ◽  
Her2 Positive ◽  
Free Survival ◽  
Distant Relapse ◽  
Time To Initiation ◽  
Increase Risk ◽  
Definitive Surgery

1022 Background: The survival benefit of adjuvant chemotherapy in breast cancer is well established. However, the optimal timing to initiation of chemotherapy after definitive surgery is unknown. We evaluated the association between time to initiation of chemotherapy and survival outcomes according to breast cancer subtype and stage at diagnosis. Methods: Women diagnosed with stage I–III breast cancer between 1997-2011 who received adjuvant chemotherapy at our institution were included. Patients were categorized according to time from definitive surgery to adjuvant chemotherapy into one of three groups: ≤ 30 days, 31–60 days and more than 60 days. Descriptive statistics, Kaplan-Meier statistics and Cox proportional hazards models were used. Results: Among the 6,827 patients included, the 5-year Overall Survival (OS), Relapse-Free Survival (RFS) and Distant Relapse-Free Survival (DRFS) estimates were similar for the different time-to-chemotherapy categories. Among patients with stage I, there was no association between outcome and time to initiation of chemotherapy. Patients with stage II disease experienced an 18% and 22% increase in risk of RFS (HR 1.18; p=0.038) and DRFS (HR 1.22; p=0.02), when systemic treatment was started >60 days from surgery. Patients with stage III disease that started adjuvant chemotherapy >60 days after surgery had a 70% increase in the risk of death (HR 1.7; p=0.002), a 32% increase risk of relapse (HR 1.32; p=0.046) and a 34% increase risk of distant relapse (HR 1.34; p=0.044). Time to chemotherapy did not have a significant effect on outcome among Hormone Receptor (HR)-positive patients. Patients with triple negative (TNBC) and HER2-positive tumors treated with trastuzumab who started chemotherapy >60 days after surgery had lower 5 year-OS estimates (HR 1.52; p=0.016 and HR 2.62; p=0.005, respectively). Conclusions: Time to chemotherapy did not influence survival outcomes in the overall population. However, patients with stage III, TNBC and HER2-positive tumors treated with trastuzumab, experienced worse outcomes when chemotherapy was delayed. Among patients with tumors with aggressive biology and more advanced stages at diagnosis, early initiation of therapy should be favored.

scholarly journals Pyrotinib in the treatment of women with advanced HER2 positive breast cancer: A multicenter, prospective, real-world study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13012-e13012
Author(s):  
Jifeng Feng ◽  
Lili Zhang ◽  
Xiaohong Wu ◽  
Jun Zhou ◽  
Mingzhen Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real World ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy Evaluation ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Her2 Breast Cancer ◽  
Positive Breast Cancer

e13012 Background: Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy of pyrotinib in patients with different baseline characteristics in the actual clinical practice has been rarely reported. This study analyzed the efficacy and safety of pyrotinib in the real world. Methods: Patients with histologically confirmed advanced HER2 positive breast cancer were included in the analyses. All patients received pyrotinib-based therapy were given pyrotinib once a day in a 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included adverse events (AE), objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Results: A total of 132 patients (median age: 52 years [29-78]) were enrolled from February 2019 to March 2020. 94(71.21%) patients had visceral metastatic lesions and 20 (15.15%) had brain metastases. HR+, HR-, or unknown HR status for primary tumor accounted for 56.82%, 42.42%, 0.76%, respectively. 115(87.12%) patients were previously administered with trastuzumab. 96(72.73%) patients received pyrotinib-based therapy as a second or further line of treatment. 94(71.21%) patients initiated pyrotinib treatment at 400 mg. Treatment regimens were pyrotinib plus capecitabine (55.30%), pyrotinib combined with trastuzumab (18.18%), and pyrotinib monotherapy (8.33%), pyrotinib combined with endocrine therapy, radiotherapy or antiangiogenic drugs (3.79%). A total of 132 patients were included in PFS analysis. mPFS was 12.0 months (95%CI 8.1-18.8). mPFS for patients without primary trastuzumab-resistant breast cancer was 14.1 months (95%CI 8.7-23.3). Patients receiving pyrotinib-based therapy as their ≥3 lines treatment had lower mPFS than those receiving pyrotinib-based therapy as their < 3 lines treatment (8.8 vs. 15.1 months, P= 0.119). mPFS in patients receiving regimen with and without capecitabine were 15.1 months and 8.4 months, respectively ( P= 0.081). As of data cutoff, mOS has not yet been reached. Among the 65 patients available for efficacy evaluation, 1 (1.54%) patient achieved complete response (CR), 24 (36.92%) patients had partial response (PR), 30 (46.15%) patients achieved stable disease (SD), and 10 (15.38%) patients had progression disease (PD), resulting in an ORR of 38.46% and DCR of 84.62%. The most common AE was diarrhea (84.17%), but only 5 (4.17%) patients were reported grade ≥ 3 diarrhea which could be well controlled. Other AEs with an incidence higher than 20.00% were anemia (36.67%), leukopenia (25.83%), vomiting (25.00%), neutropenia (22.50%). No treatment-related death occurred. Conclusions: Pyrotinib demonstrated an encouraging efficacy and manageable safety in patients with advanced HER2+ breast cancer. More data would be analyzed and reported in the future. Clinical trial information: ChiCTR1900021819.

scholarly journals Preoperative Systemic Therapy Versus Upfront Surgery in HER2-Positive Breast Cancer in the Real World

2021 ◽  
Vol 11 ◽  
Author(s):  
Xingfei Yu ◽  
Chen Wang ◽  
Yabing Zheng ◽  
Beibei Miao ◽  
Jiejie Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real World ◽  
Systemic Treatment ◽  
Disease Free Survival ◽  
Her2 Positive ◽  
Free Survival ◽  
Inverse Probability ◽  
Surgery Group ◽  
Significant Difference ◽  
Disease Free

PurposeTo compare survival in different strategies, preoperative systemic treatment versus upfront surgery, in HER2-positive early breast cancer patients in the real world.MethodsAccording to the actual upfront treatment, eligible patients from 2012 to 2015 were classified as preoperative systemic treatment or upfront surgery group prospectively. The primary endpoint is disease-free survival; the second endpoint is overall survival. All the outcomes were examined in the propensity score matching model and inverse probability of treatment weighting model.ResultsIncluded in the analysis were 1,067 patients (215 in the preoperative systemic treatment group, 852 in the upfront surgery group). In the propensity score matching model (matching at 1:1 ratio), the disease-free survival of the preoperative systemic treatment group was significantly higher than that of the upfront surgery group (hazard ratio, 0.572, 95%CI, 0.371–0.881, P, 0.012). In the inverse probability of treatment weighting model, there was no significant difference in disease-free survival between the two groups (hazard ratio, 0.946, 95%CI, 0.763–1.172, P, 0.609). For overall survival, there was no significant difference between the two groups.ConclusionThe HER2-positive patients who accepted preoperative systemic treatment had better disease-free survival than those who underwent upfront surgery by real-world statistic methods.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT04249440.

HER2, TOP2A, and TIMP-1 and Responsiveness to Adjuvant Anthracycline-Containing Chemotherapy in High-Risk Breast Cancer Patients

2010 ◽  
Vol 28 (6) ◽  
pp. 984-990 ◽  
Author(s):  
Bent Ejlertsen ◽  
Maj-Britt Jensen ◽  
Kirsten V. Nielsen ◽  
Eva Balslev ◽  
Birgitte B. Rasmussen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Free Survival

Purpose To evaluate whether the combination of HER2 with TIMP-1 (HT) or TOP2A with TIMP-1 (2T) more accurately identifies patients who benefit from cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with cyclophosphamide, methotrexate, and fluorouracil (CMF) than these markers do when analyzed individually. Patients and Methods The Danish Breast Cancer Cooperative Group (DBCG) 89D trial randomly assigned 980 high-risk Danish breast cancer patients to CMF or CEF. Archival tumor tissue was analyzed TIMP-1, and HER2-negative and TIMP-1 immunoreactive tumors were classified as HT nonresponsive and otherwise HT responsive. Similarly, the 2T panel was constructed by combining TOP2A and TIMP-1; tumors with normal TOP2A status and TIMP-1 immunoreactivity were classified as 2T-nonresponsive and otherwise 2T-responsive. Results In total, 623 tumors were available for analysis, of which 154 lacked TIMP-1 immunoreactivity, 188 were HER2 positive, and 139 had a TOP2A aberration. HT status was a statistically significant predictor of benefit from CEF compared with CMF (Pinteraction = .036 for invasive disease–free survival [IDFS] and .047 for overall survival [OS]). The 269 (43%) patients with a 2T-responsive profile had a significant reduction in IDFS events (adjusted hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P < .001) and OS events (adjusted hazard ratio, 0.54; 95% CI, 0.38 to 0.77; P < .001). 2T status was a highly significant predictor of benefit from CEF compared with CMF (Pinteraction < .0001 for IDFS and .004 for OS). Conclusion The 2T profile is a more accurate predictor of incremental benefit from anthracycline-containing chemotherapy than HER2, TIMP-1, or TOP2A individually, and compared with these, 2T classifies a larger proportion of patients as sensitive to anthracyclines.

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