Clinical factors associated with overall survival (OS) for patients with HER2-positive (HER2+) metastatic breast cancer (MBC) treated with HER2-targeting systemic therapy (HER2Tx)

2017 ◽  
Vol 72 ◽  
pp. S44
Author(s):  
G. Gullo ◽  
N. Walsh ◽  
A. Zacchia ◽  
L. Hammond ◽  
D. Fennelly ◽  
...  
2021 ◽  
Vol 9 (07) ◽  
pp. 422-428
Author(s):  
Rafaela Aparecida Dias de Oliveira ◽  
Lyvia Aparecida Dias de Oliveira ◽  
Marília Davoli Abella Goulart ◽  
Maria Clara Faustino Linhares

Introduction: In advanced breast cancer, local treatment is considered palliative. However, although there are some polemic opinions about the surgical treatment, some of the latest studies have emphasized that in advanced cases primary tumor resection (PTR) is related to better outcomes. This review aims to evaluate how resection of the original tumor impacts women with metastatic breast cancer, considering the most recent studies about this subject. Methods: The search was performed in MEDLINE, Scopus, PMC, Current Contents and Wiley Online Library databases; 23 articles - from 2016 to 2019 - were selected and 11 were included in this review. As inclusion criteria were considered: studies presenting outcomes about resection of the primary tumor, comparison between chemotherapy/ hormone therapy/ targeted cancer therapies and surgical intervention, studies published from 2016 to 2019 and available in English, Spanish or Portuguese. We excluded those which did not approach PTR, did not present outcomes of interest (progression-free survival comparison between PTR and systemic therapy) or only discussed systemic therapy, as well as those published before 2016. Results: It was reported in 6 studies that progression-free survival is better on those who underwent surgery. PTR was also related to longer median overall survival in women submitted to surgery, up to 16 months higher when compared to the ones who were not. Enhanced survival even pertained to surgical groups regardless of tumor size.  Conclusion: Based in the analysis, PTR in metastatic breast cancer can be related to higher overall survival.


Author(s):  
Toshiaki Iwase ◽  
Tushaar Vishal Shrimanker ◽  
Ruben Rodriguez-Bautista ◽  
Onur Sahin ◽  
Anjali James ◽  
...  

The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype, and exhibited a tendency toward improvement over time for the ER-negative (ER-)/HER2+ subtype. Median OS was significantly longer in patients with non-inflammatory breast cancer (P = .02) and in patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all P <.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11092-11092
Author(s):  
K. Leitzel ◽  
H. Y. Hou ◽  
V. Shrivastava ◽  
U. Anyanwu ◽  
S. M. Ali ◽  
...  

11092 Background: Approximately half of HER2-positive breast cancer patients will respond to first-line trastuzumab-containing therapy. However, in those patients with an initial trastuzumab response, most will progress within a year with acquired resistance. Since trastuzumab treatment is also now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a vexing clinical problem, and better predictive and prognostic biomarkers are urgently needed. Methods: Serum HER2, tissue inhibitor of metalloproteinase-1 (TIMP-1), urokinase-type plasminogen activator (uPA), CA9, VEGF-165, and endoglin were measured using ELISA assays in 66 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. The HER2, TIMP-1, uPA, CA9, and VEGF-165 ELISAs were from Oncogene Science/Siemens Healthcare Diagnostics, Cambridge, MA; and the endoglin ELISA was from R&D Systems, Minneapolis, MN. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with continuous pretreatment serum biomarker variables. Results: Pretreatment serum HER2 (p= 0.005), TIMP-1 (p< 0.0001), uPA (p= 0.006), endoglin (p= 0.008), and CA9 (p <0.0001) were all significant as univariate continuous biomarkers for predicting PFS to first-line trastuzumab-containing therapy, but VEGF was not. In multivariate analysis for PFS with all six biomarkers, only serum CA9 (p= 0.002) was a significant independent covariate. For OS, pretreatment serum HER2 (p= 0.018), TIMP-1 (p< 0.0001), uPA (p< 0.0001), endoglin (p= 0.002), and CA9 (p< 0.0001) were all significant as univariate continuous biomarkers for prognosis, but serum VEGF was not. In multivariate analysis for OS with all six biomarkers, only serum CA9 was a significant independent prognostic covariate (p= 0.001). Conclusions: Elevated pretreatment serum CA9 (a marker of hypoxia) predicts reduced progression-free survival and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. These serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment. Supported by a grant from Komen for the Cure. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1024-1024 ◽  
Author(s):  
Ayesha Ali ◽  
Laura Krecko ◽  
Kim Leitzel ◽  
Suhail M. Ali ◽  
Joseph J. Drabick ◽  
...  

1024 Background: Recently the immune checkpoint inhibitors (ICIs) have demonstrated efficacy across a wide variety of cancers, but have been less effective in breast cancer. PD-L1 (B7-H1, CD274) is a ligand produced by many tumor cells and some immune cells, and suppresses the T cell immune response. This allows tumor cells to escape immune detection. PD-L1 is used as a companion tumor tissue IHC biomarker for patient selection for some of the FDA-approved ICIs (pembrolizumab), but not for others (nivolumab, atezolizumab). Circulating PD-L1 has been detected in multiple myeloma, renal, lung, and gastric cancer, but not in breast cancer. Here we correlated serum PD-L1 levels with outcome in a HER2-positive metastatic breast cancer cohort treated with trastuzumab. Methods: Pretreatment serum was obtained from 63 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. A novel ELLA microfluidic channel immunoassay platform (ProteinSimple, San Jose, CA) was employed to quantitate serum PD-L1. Serum PD-L1 levels were analyzed using continuous, quartile, and dichotomous (25%, median, and 75%) cutpoints. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Results: On a continuous basis, patients with higher serum PD-L1 had a significantly reduced PFS (p = 0.045) and overall survival OS (p = 0.004) compared to patients with lower serum PD-L1 levels. Patients with the higher quartiles of serum PD-L1 also trended to have reduced PFS (0.11) and significantly reduced OS (p = 0.015) compared to the lower quartiles of serum PD-L1. Finally, using either the 25th or 75th percentile of serum PD-L1 as dichotomous cutpoint, patients with higher serum PD-L1 had significantly reduced OS (p = 0.04). Conclusions: Higher circulating PD-L1 levels were prognostic for reduced PFS and OS in HER2-positive metastatic breast cancer patients treated with first-line trastuzumab. Circulating PD-L1 deserves further study for prognostic and predictive biomarker utility in larger trials of immune checkpoint inhibitors and other immunotherapies in breast and other cancers. AA, LK contributed equally.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13034-e13034
Author(s):  
Robert Shenk ◽  
Lifen Cao ◽  
Jonathan T. Bliggenstorfer ◽  
James Michael Martin ◽  
Megan E. Miller

e13034 Background: Current ASCO guidelines recommend endocrine therapy as preferred primary treatment for hormone receptor positive (HR+) metastatic breast cancer (MBC). We assessed survival outcomes of HR+/HER2- MBC patients undergoing endocrine therapy with and without chemotherapy. Methods: The National Cancer Database was queried 2004-2016 for patients with de novo HR+/HER2- MBC. Exclusion criteria were treatment with surgery or radiation at the primary site and missing oncologic and follow up data. Overall survival was compared between systemic treatment groups using multivariable cox proportional hazards regression modes. Results: 19,317 patients met inclusion criteria, among whom 2,360 (12%) received no systemic therapy, 2,617 (14%) received chemotherapy only, 10,078 (52%) received endocrine therapy only and 4,262 (22%) received both chemotherapy and endocrine therapy. Patients treated with chemotherapy only more frequently had lung (38%, p<0.001) or liver (36%, p<0.001) metastasis while those undergoing endocrine therapy only presented primarily with bone metastasis (82%, p<0.001). Patients with multiple metastatic sites more often received endocrine therapy alone than combined therapy (44 vs. 25%, p<0.001). Median overall survival was similar after combination therapy and endocrine therapy, and poorest after chemotherapy alone (33.1 vs 31.4 vs 19.8 months, p<0.001). After controlling for patient, facility, and tumor characteristics, endocrine therapy alone provided superior survival benefit to chemotherapy only, though combination systemic therapy resulted in the greatest overall survival (p<0.001). Conclusions: Primary endocrine therapy provided significant survival benefit over chemotherapy alone for HR+/HER2- MBC. Though combination systemic therapy may be warranted in progressive disease, our results align with recommendations for endocrine therapy as first line treatment for HR+/HER2- MBC. [Table: see text]


2012 ◽  
Vol 30 (21) ◽  
pp. 2585-2592 ◽  
Author(s):  
Kimberly L. Blackwell ◽  
Harold J. Burstein ◽  
Anna Maria Storniolo ◽  
Hope S. Rugo ◽  
George Sledge ◽  
...  

Purpose Phase III EGF104900 data demonstrated that lapatinib plus trastuzumab significantly improved progression-free survival (PFS) and clinical benefit rate versus lapatinib monotherapy, offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer (MBC). Final planned overall survival (OS) analysis from EGF104900 is reported here. Patients and Methods Patients with HER2-positive MBC whose disease progressed during prior trastuzumab-based therapies were randomly assigned to receive lapatinib monotherapy or lapatinib in combination with trastuzumab. OS and updated PFS data are presented using Kaplan-Meier curves and log-rank tests stratified for hormone receptor and visceral disease status. Subgroup analyses were conducted to identify characteristics of patients deriving the greatest clinical benefit. Results In this updated final analysis of all patients randomly assigned with strata (n = 291), lapatinib plus trastuzumab continued to show superiority to lapatinib monotherapy in PFS (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .011) and offered significant OS benefit (HR, 0.74; 95% CI, 0.57 to 0.97; P = .026). Improvements in absolute OS rates were 10% at 6 months and 15% at 12 months in the combination arm compared with the monotherapy arm. Multiple baseline factors, including Eastern Cooperative Oncology Group performance status of 0, nonvisceral disease, < three metastatic sites, and less time from initial diagnosis until random assignment, were associated with improved OS. Incidence of adverse events was consistent with previously reported rates. Conclusion These data demonstrated a significant 4.5-month median OS advantage with the lapatinib and trastuzumab combination and support dual HER2 blockade in patients with heavily pretreated HER2-positive MBC.


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