scholarly journals Title Does Definitive Local Therapy Offer Cure in Select HER2+ De Novo Metastatic Breast Cancer Patients Treated with Dual Anti-HER2 Blockade?

Author(s):  
Luderve Rosier ◽  
Youth Wang ◽  
Jihyun Lee ◽  
Karen Daily

Abstract Purpose: The role of surgery with curative intent in HER2+ de novo metastatic breast cancer (dnMBC) is uncertain in the era of dual antibody therapy. We sought to determine from existing retrospective data current practice patterns and if an association exists between surgery to the primary tumor and improved survival in HER2+ dnMBC patients treated with dual anti-HER2 blockade, accounting for selection bias.Methods: This study employed data from the National Cancer Database (NCDB) from the years 2013 to 2015. Study inclusion was limited to adult women with HER2+ dnMBC, who received immunotherapy/biologic response modifier drugs (BRM) as a first line treatment. Patients who received both systemic therapy and surgery to the primary breast tumor and patients who received systemic therapy alone were analyzed in two groups. Chi-square test for discrete variables and Wilcox on Rank-Sum test for numeric variables was used to compare the two groups based on patient, tumor, and treatment characteristics. The primary endpoint was overall survival from the time of diagnosis to the time of death.Results: 928 women with HER2+ dnMBC treated with BRM were identified with 43.5% (n= 404) receiving surgery and 56.5% (n= 524) receiving systemic therapy alone. The 3-year overall survival was superior for the surgery group (74.1%, 95% CI 67.9-79.2%) compared to the no surgery group (53.3%; 95% CI 47.6-58.6%). The no surgery group had median overall survival of 39.8 months (95% CI 34.1-44.9), while the surgery group had not yet reached median overall survival.Conclusion: In a group of HER2+ dnMBC patients receiving systemic treatment in the era of dual antibody therapy, patients who underwent surgery had a superior 3-year survival rate than those who did not. There may be a role for HER2+ dnMBC patients with an excellent response to dual HER2 blockade to undergo curative intent local therapy to the primary tumor.

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.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 625-625
Author(s):  
Mark Danese ◽  
Deepa Lalla ◽  
Melissa Brammer ◽  
Eduardo Santos ◽  
Abraham Lee ◽  
...  

625 Background: Trastuzumab was approved in the United States (US) in September 1998 for the treatment of HER2+ metastatic breast cancer (MBC). This model estimates the total number of life years saved (LYS) in US women treated with trastuzumab over a 15-year period (1999-2013). Methods: Using US population estimates and cancer registry-based incidence data, we estimated the number of women with recurrent stage I-III or de novo stage IV HER2+ MBC by year, age, hormone receptor, and nodal status. Trastuzumab utilization was based on published studies of HER2 testing rates, true positive rates in the community, and treatment initiation rates. Survival was estimated by extrapolating survival data pooled across 5 trials and 2 observational studies separately for women treated with trastuzumab and with chemotherapy alone. Few studies reported survival in women with HER2+ MBC without trastuzumab (N=3). Sensitivity analyses were conducted by estimating overall survival from the initial phase 3 trial (67% of placebo patients crossed over to trastuzumab after progression; HR=0.80), and assuming a higher risk reduction to account for crossover effects in clinical trials (HR=0.60). Results: In the base case, approximately 83,462 women with HER2+ MBC were estimated to receive 1st line trastuzumab over a 15-year period. The pooled median overall survival across studies without and with trastuzumab was 21.2 and 35.5 months, respectively. Patients were projected to live a total of 216,290 life years if trastuzumab had not been available and if they received chemotherapy only. These same patients were estimated to live a total of 294,877 life years with first-line trastuzumab, for an incremental benefit of 78,587 LYS. In sensitivity analysis, total LYS ranged from 48,334-96,360. Conclusions: Real-world evidence supports a median overall survival of approximately 36 months in women with HER2+ MBC receiving 1st line trastuzumab. Using a population-based, conservative model, we found that trastuzumab use has resulted in > 75,000 life years over 15 years in women with HER2+ MBC. Future research is warranted to examine the characteristics, experiences, and outcomes among women living longer with HER2+ MBC.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 136-136 ◽  
Author(s):  
Gwenaelle Gravis ◽  
Jean-Marie Boher ◽  
Yu-Hui Chen ◽  
Glenn Liu ◽  
Karim Fizazi ◽  
...  

136 Background: Patients with a low burden of metastatic disease and who relapse after localized therapy with curative intent have a longer overall survival. It is unclear whether these patients benefit from early docetaxel (D). Methods: Patients in GETUG-AFU15 (N = 385, median follow-up 84 mo) and CHAARTED (N = 790, median follow up 54 mo) were randomized to ADT alone or ADT + D and outcomes described using the same definition of high volume (HV) and low volume (LV) disease. (HV: visceral metastases and/or 4 or more bone metastases with at least one outside the axis) and whether the patients had prior local therapy or not. Results: Table 1 details across both studies that de novo HV group treated with ADT alone has the shortest overall survival and D has a consistent effect in improving OS. In contrast, in both studies patients with LV disease had a much longer OS with no evidence that D improved OS. Conclusions: There was no apparent survival benefit in CHAARTED and GETUG-15 studies with D for LV whether patients had prior local treatment or not. Across both studies, early D had a consistent effect and improved OS in HV pts especially those with no prior local therapy. Partial Support and drug supply by Sanofi. Clinical trial information: NCT00104715, NCT00309985. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12549-e12549
Author(s):  
Giorgio Mustacchi ◽  
Paolo Pronzato ◽  
Grazia Arpino ◽  
Alessia D'Alonzo ◽  
Michela Piezzo ◽  
...  

e12549 Background: TNBC shows a very bad prognosis: median time to relapse is 18 months and median overall survival (OS) is less than 24 months. Methods: AMBRA is a longitudinal cohort study, describing the choice of 1st- and subsequent treatments in HER2-ve MBC pts in the years 2012-2015. The present analysis is focused on TNBC pts (127 out of 879 evaluable; 14.4%) and CHT strategies, overall and according to adj treatment. Kaplan Meyer probability of survival from primary (DFS), 1st (PFS1) and 2nd (PFS2) progression and Time from last CHT and death were calculated for the whole population and according the main adj regimens. Results: Median age at primary diagnosis was 53 years. The most used regimens in the adj setting were anthra/taxane(tax) 50.7%, anthra 22.1% or others (CMF included) 20.6%). Median time to events was: DFS 23.2, PFS16.5 and PFS2 4.3 months, respectively. CHT choices in the metastatic setting according to adj treatment were: Conclusions: Our results show that taxanes play a crucial role in MBC even if used in 50% of Adj. CAPE/VRL, Platinum regimens and Eribuline are also widely used. Time from last CHT administration and Death is very short in 30% of cases[Table: see text]


2020 ◽  
Author(s):  
Sun Jianna ◽  
Kong Lingjun ◽  
Feng Nana ◽  
Liu Hong ◽  
Ren Chongxi

Abstract Background: In an earlier analysis of this cohort study, local therapy based on surgical resection of the primary tumor might confer a survival benefit in women with de novo metastatic breast cancer (dnMBC). Here we report the survival outcomes of locoregional treatment (LRT), focusing on the association of surgical timings and surgical margins with survival in these patients. Methods: The retrospective study included patients with dnMBC in two Chinese tertiary hospitals, between March 1, 2007, and December 31, 2017. Overall survival (OS) was evaluated by means of a stratified log-rank test and summarized with the use of Kaplan–Meier methods. Results: A total of 153 patients were included, of whom 87 underwent LRT and 66 systemic therapy alone (STA). LRT showed a significant OS benefit over STA (HR, 0.47; 95% CI, 0.33 to 0.69; p<.0001). Median OS of LRT group and STA group were 42 months (95% CI, 35.0 to 48.9 months) and 21 months (95% CI, 16.1 to 25.9 months), respectively. The benefit was consistent across most subgroups. The OS of patients undergoing surgery was better than that of patients without surgery (HR, 0.48; 95% CI, 0.33 to 0.70; p=.0001), and there was difference in survival improvement at different surgical timings (surgery before chemotherapy, during chemotherapy and after chemotherapy) (HR, 0.79; 95% CI, 0.65 to 0.95; p=.013). The survival benefit of surgery after chemotherapy was the most, followed by surgery during chemotherapy (Median 56 months, 95% CI, 40.8 to 71.2 months). Moreover, compared with patients with positive margins, the OS of patients with negative margins was significantly improved (HR, 2.35; 95% CI, 1.65 to 3.35; p<.0001), with a median OS of 56 months (95% CI, 45.9 to 66.1 months). Conclusions: Our results suggest that LRT is associated with improved OS in women with dnMBC, and patients who had surgery after or during systemic chemotherapy with negative surgical margins, are expected to benefit more.


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]


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