Early efficacy analysis of the AE37 vaccine in patients with HER2 low-expressing and triple-negative breast cancer.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 109-109 ◽  
Author(s):  
Elizabeth Ann Mittendorf ◽  
Sonia A. Perez ◽  
Diane F. Hale ◽  
Timothy J. Vreeland ◽  
Alan K. Sears ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Reduction ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Phase Iii ◽  
Control Group ◽  
Her2 Expression ◽  
Gm Csf ◽  
Helper Epitope ◽  
Disease Free

109 Background: Peptide vaccines comprised of HLA class II epitopes, which elicit CD4+ T cell responses, play a critical role in potentiating immune responses. We are conducting a randomized phase II trial of AE37, a hybrid peptide created by the addition of the Ii-Key moiety (LRMK) to the HER2 helper epitope, AE36 (HER2 aa776-790). Here, we present efficacy data focusing on outcomes in patients with low HER2 (IHC 1+ or 2+) expression and triple negative breast cancer (TNBC). Methods: The trial is enrolling node positive or high risk node negative breast cancer patients with any degree of HER2 expression (IHC 1+, 2+ or 3+ or FISH > 1.2) rendered disease-free following standard of care therapy. Patients are randomized to receive either AE37+GM-CSF or GM-CSF alone in 6 monthly intradermal inoculations followed by booster inoculations administered every 6 months. Results: The trial has enrolled 254 patients; 105 in the vaccine group (VG) and 149 in the control group (CG). After a median follow-up of 22.3 months, the disease-free survival (DFS) rate in the VG is 90.3% vs 81.1% in the CG (p=.46), a 49% risk reduction. Evaluating patients with low HER2 expression (IHC 1+ or 2+), there are 53 VG patients and 77 CG patients. The groups are well-matched with respect to the percentage of patients with high grade tumors, tumors > 2cm, the rate of node positivity and ER/PR status (all p>.5). The DFS rate in the VG of low HER2 expressers is 89.8% vs 68.2% in the CG (p=.12), a 68% risk reduction. When limiting analyses to patients with TNBC (ER/PR negative, HER2 1+ or 2+), there are 13 VG patients and 23 CG patients. The groups are again well-matched with the exception of control patients having a larger percentage of tumors > 2 cm (70% vs 31%; p=.02). The DFS rate in the VG of TNBC patients is 83.3% vs 47.6% in the CG (p=.23), a 68% risk reduction. Conclusions: Early analyses suggest clinical benefit to vaccination with AE37, particularly in patients with low HER2-expressing tumors. Importantly, the benefit appears to persist in TNBC patients. Patients will continue to be followed per protocol for 5 years; however, these data suggest that a subsequent phase III trial should evaluate the vaccine in patients with low HER2-expressing disease to include TNBC.

Subgroup efficacy evaluation of the AE37 HER2 vaccine in breast cancer patients in the adjuvant setting.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3088-3088 ◽  
Author(s):  
Kaitlin M. Peace ◽  
Elizabeth Ann Mittendorf ◽  
Sonia A. Perez ◽  
Panagiotis Tzonis ◽  
Nikolaos Fragkiskos Pistamaltzian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Her2 Expression ◽  
Breast Cancer Patients ◽  
Adjuvant Setting ◽  
Gm Csf ◽  
Significant Difference ◽  
Disease Free

3088 Background: AE37 is a Ii-Key hybrid of the HER2 peptide AE36 (HER2776-790), which stimulates peptide-specific T cells. We have completed the active phase of a prospective, randomized, multi-center, phase II trial of the AE37 vaccine in the adjuvant setting. The primary analysis, performed after a median follow up (f/u) of 25 months (mo), did not show a significant difference in disease free survival (DFS) between vaccinated and control patients (pts). However, demonstrating the efficacy of cancer vaccines may require more time than other therapies, especially in malignancies with relatively late recurrences like breast cancer. Here, we present updated efficacy data after extended f/u in subgroups of pts stratified by clinicopathologic characteristics. Methods: Clinically disease-free, node positive or high-risk node negative pts with any level of HER2 expression were randomized to receive AE37 + GM-CSF (VG) or GM-CSF alone (CG) following standard of care therapy. Pts received 6 monthly intradermal inoculations during the primary vaccine series (PVS) followed by 4 boosters administered every 6 mo. Kaplan Meier and log rank analyses were performed from the time of the first inoculation in pts who completed at least the PVS, according to stage, node status, tumor size, HER2 expression and ER/PR status. Results: There were no clinicopathologic differences between groups in the 298 enrolled pts (VG = 153, CG = 145). The vaccine is safe and well tolerated. After a median f/u of 55 mo, there was a trend toward improved DFS in the VG among stage IIB/III pts (VG, n = 73, DFS 82% vs CG, n = 61, 67%, HR = 0.48, p = 0.06) and those with low HER2 expression (HER2 LE, VG, n = 68, 89% vs CG, n = 66, 51%, HR = 0.47, p = 0.1). Improved DFS in the VG was documented in patients with both stage IIB/III disease and HER2 LE (VG, n = 39, 90% vs CG, n = 38, 32%, HR 0.3, p = 0.02) and triple negative (TNBC) pts (VG, n = 21, 89% vs CG, n = 21, 0%, HR 0.26, p = 0.05). Conclusions: The AE37 vaccine is safe and well tolerated and has statistically significant efficacy in stage IIB/III pts with HER2 LE and in TNBC pts. This justifies further evaluation in a phase III study enrolling stage IIb/III pts not eligible for trastuzumab treatment and the very high risk TNBC group. Clinical trial information: NCT00524277.

Development of prognostic nomograms using institutional data for patients with triple-negative breast cancer

2021 ◽  
Author(s):  
Jie-Yu Zhou ◽  
Kang-Kang Lu ◽  
Wei-Da Fu ◽  
Hao Shi ◽  
Jun-Wei Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Predictive Accuracy ◽  
Area Under The Curve ◽  
Disease Free Survival ◽  
Discriminative Ability ◽  
Free Survival ◽  
Disease Free

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

scholarly journals Alteration in Steroid Hormone and HER2/neu Receptor Status Following Neoadjuvant Chemotherapy in Triple Negative Breast Cancer. Is There Any Hope?

2021 ◽  
Author(s):  
Rama Das ◽  
Parna Basu ◽  
Suman Ghosh ◽  
Debasish Guha
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Control Group ◽  
Study Group ◽  
Residual Tumour ◽  
Receptor Status ◽  
Platinum Based Chemotherapy

Introduction: Breast cancer continues to be the most common cancers among women in India. The Triple Negative Breast Cancer (TNBC) is a heterogeneous group of malignancy which is often aggressive and has a worse prognosis. Aim: The aim of this study was to assess the hormone receptor and HER2/neu status with platinum based chemotherapy in TNBC. Materials and Methods: The study was analysed retrospectively in a tertiary care centre of West Bengal from Januay 2017 to December 2019. Forty TNBC patients of Locally Advanced Breast Cancer (LABC) cases who received carboplatin along with neoadjuvant chemotherapy (study group) were compared with other group of 64 TNBC patients (control group) who did not receive any chemotherapy making a total of 104 cases of TNBC patients who were selected for the study. All the patients in both the groups had modified radical mastectomy. The study group of 40 TNBC patients who received chemotherapy also showed pathological partial response. Masterchart was prepared comprising patient’s age, menopausal status, family history, therapy history, histo-morphological features, hormone receptor and HER2/neu status after platinum added chemotherapy. Oestrogen Receptor (ER)/Progesterone Receptor (PR) were considered positive, if >1% tumour cell nuclei were immunoreactive and negative, if it was otherwise. HER-2/neu score of 3+ was taken as positive by Immunohistochemistry (IHC) method. Statistical analysis for descriptive purposes, percentages and mean were calculated. Comparison of both the groups was done by Pearson’s Chi-squared and Fisher’s-exact test. Significance level was considered at p-value <0.05. Results: TNBC patients (NACT group) showed hormone receptor positivity of 21 cases (52.50%) after chemotherapy along with carboplatin. HER2/neu positivity was detected in 9 (22.5%) cases. Non-NACT (64) cases were considered as control group for comparison. The effect of NACT in TNBC patients was found to be statistically significant with respect to change in HER2/neu (p=0.033, p<0.05) and ER status (p<0.05) while change in PR status was found to be statistically insignificant. Conclusion: The study showed significant alteration in hormonal and HER2/neu receptor status in TNBC patients receiving platinum added neoadjuvant chemotherapy. This study found statistical significance and justifies re-evaluation of these Hormone Receptor (HR) and HER2/neu markers in residual tumour after chemotherapy.

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer

2020 ◽  
pp. 106002802096654
Author(s):  
John M. Seligson ◽  
Alexandra M. Patron ◽  
Michael J. Berger ◽  
R. Donald Harvey ◽  
Nathan D. Seligson
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
English Language ◽  
Triple Negative ◽  
Data Extraction ◽  
Phase Iii ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Topoisomerase 1 ◽  
Antibody Drug

Objective: To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease. Data Sources: A literature search was conducted utilizing PubMed and MEDLINE databases, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and September 3, 2020. Keywords included sacituzumab govitecan (-hziy), IMMU-132, Trop-2 (trophoblast cell-surface antigen 2), and TACSTD2. Study Selection and Data Extraction: All English-language trials involving sacituzumab govitecan for mTNBC were included and discussed. Data Synthesis: Sacituzumab govitecan is an antibody-drug conjugate targeted for Trop-2 and conjugated to the topoisomerase-1 inhibitor SN-38. It was granted accelerated Food and Drug Administration approval based on a phase I/II single-arm, multicenter study (n = 108), which reported an overall response rate of 33.3% and median duration of response of 7.7 months (95% CI = 4.9-10.8 months). Common adverse reactions include nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, abdominal pain, and respiratory infection. A confirmatory, randomized phase III clinical trial is ongoing (NCT02574455). Relevance to Patient Care and Clinical Practice: This review covers the efficacy, safety, and clinical use of sacituzumab govitecan, a third-line drug with activity in mTNBC. Conclusion: Sacituzumab govitecan is a novel targeted treatment with promising activity in mTNBC.

scholarly journals Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Claire H. Li ◽  
Vassiliki Karantza ◽  
Gursel Aktan ◽  
Mallika Lala
Keyword(s):  
Breast Cancer ◽  
Literature Review ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Meta Analysis ◽  
Phase Iii ◽  
Subgroup Analyses ◽  
Phase Iii Trials ◽  
Phase Iii Study ◽  
Locally Recurrent

Abstract Background Metastatic triple-negative breast cancer (mTNBC), an aggressive histological subtype, has poor prognosis. Chemotherapy remains standard of care for mTNBC, although no agent has been specifically approved for this breast cancer subtype. Instead, chemotherapies approved for metastatic breast cancer (MBC) are used for mTNBC (National Comprehensive Cancer Network Guidelines [NCCN] v1.2019). Atezolizumab in combination with nab-paclitaxel was recently approved for programmed death-ligand 1 (PD-L1)–positive locally advanced or metastatic TNBC. Published historical data were reviewed to characterize the efficacy of NCCN-recommended (v1.2016) agents as first-line (1L) and second-line or later (2L+) treatment for patients with locally recurrent inoperable or metastatic TNBC (collectively termed mTNBC herein). Methods A systematic literature review was performed, examining clinical efficacy of therapies for mTNBC based on NCCN v1.2016 guideline recommendations. Data from 13 studies, either published retrospective mTNBC subgroup analyses based on phase III trials in MBC or phase II trials in mTNBC, were included. Results A meta-analysis of mTNBC subgroups from three phase III trials in 1L MBC reported pooled objective response rate (ORR) of 23%, median overall survival (OS) of 17.5 months, and median progression-free survival (PFS) of 5.4 months with single-agent chemotherapy. In two subgroup analyses from a phase III study and a phase II trial (n = 40 each), median duration of response (DOR) to 1L chemotherapy for mTNBC was 4.4–6.6 months; therefore, responses were not durable. A meta-analysis of seven cohorts showed the pooled ORR for 2L+ chemotherapy was 11% (95% CI, 9–14%). Median DOR to 2L+ chemotherapy in mTNBC was also limited (4.2–5.9 months) per two subgroup analyses from a phase III study. No combination chemotherapy regimens recommended by NCCN v1.2016 for treatment of MBC showed superior OS to single agents. Conclusions Chemotherapies have limited effectiveness and are associated with unfavorable toxicity profiles, highlighting a considerable unmet medical need for improved therapeutic options in mTNBC. In addition to the recently approved combination of atezolizumab and nab-paclitaxel for PD-L1–positive mTNBC, new treatments resulting in durable clinical responses, prolonged survival, and manageable safety profile would greatly benefit patients with mTNBC.

scholarly journals Immunotherapy in Triple-Negative Breast Cancer: Present and Future

2019 ◽  
Vol 11 (4) ◽  
pp. 259-271 ◽  
Author(s):  
Isaac Kim ◽  
Katherine Sanchez ◽  
Heather L. McArthur ◽  
David Page
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Survival Benefit ◽  
Triple Negative ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Phase Iii ◽  
Breast Cancers ◽  
Effective Treatment Option

Abstract Purpose of Review Immunotherapy is emerging as an effective treatment option for metastatic triple-negative breast cancer. In this review, we summarize clinical data of immunotherapy in triple-negative breast cancer and comment on future directions in the field. Recent Findings IMpassion130 was a phase III trial that demonstrated progression-free survival benefit, and potentially overall survival benefit, of first-line chemotherapy (nab-paclitaxel) plus anti-programmed death ligand 1 (PD-L1) atezolizumab, among PD-L1-positive metastatic triple-negative breast cancers. Studies are ongoing to evaluate other combination therapies with immune checkpoint blockade in TNBC, and to evaluate efficacy in PD-L1-negative tumors and in later lines of therapy. Summary Immunotherapy is now a standard option in the treatment of triple-negative breast cancer. Ongoing trials may expand the degree of clinical benefit. Further work is ongoing to identify novel predictive biomarkers, which in the future may enable a personalized approach of combination immunotherapy.

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