scholarly journals US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments

2018 ◽  
Vol 36 (12) ◽  
pp. 1225-1231 ◽  
Author(s):  
Suparna B. Wedam ◽  
Julia A. Beaver ◽  
Laleh Amiri-Kordestani ◽  
Erik Bloomquist ◽  
Shenghui Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastases ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Differential Outcomes ◽  
Discordance Rate ◽  
Trial Outcomes ◽  
The Impact

Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5% (range: 4% to 26%), dependent on subtype. Investigator-assessed progression-free survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBM PFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.

scholarly journals Metastatic Breast Cancer: Is There a Differential Therapy Efficacy between Visceral and Non-Visceral Metastatic Breast Cancer?

Breast Care ◽  
2019 ◽  
Vol 15 (5) ◽  
pp. 527-533
Author(s):  
Thomas Kolben ◽  
Maximilian Bardenhewer ◽  
Theresa M. Kolben ◽  
Laura Rickerl ◽  
Tom Degenhardt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Phase Iii ◽  
Professional Information ◽  
The Impact ◽  
Visceral Disease

Purpose: Differential efficacy of newly registered therapies in subgroups of metastatic breast cancer (MBC) is an important consideration for subsequent use in clinical practice. Unfortunately, such subgroup analyses often are exploratory and rarely statistically adequately powered and may thus be misleading. This analysis aimed to explore a potentially different treatment response to i.v. therapies between visceral and non-visceral MBC. Methods: In a systematic literature analysis (PubMed) comprising phase III registration studies for MBC from 1994 to 2014, differences in outcome were evaluated regarding progression-free survival, time to progression, overall survival (OS), and visceral versus non-visceral disease. The impact of HER2 and hormone receptor status was also considered. A total of 16 studies comprising 13,083 patients were selected by considering the information given in the medical product’s professional information and the decision of the US Food and Drug Administration or the European Medicine Agency for approval of the respective therapeutic agents now used in the treatment of MBC. Results: No statistically significant differences regarding treatment response and therapy benefit were found in MBC patients with visceral versus non-visceral metastases based on reported hazard ratios and confidence intervals in registration trials. Interesting but nonsignificant differences were found regarding a distinct therapy benefit regarding different metastasis locations in 4 studies. Conclusion: For targeted i.v. therapies based on biomarker selection, there is a trend – although not significant – toward a benefit (OS) from combination therapies favoring visceral disease. However, at the present time, metastasis localization should not be used as a predictive marker for choice of systemic therapy in MBC.

Impact of loco-regional treatment including radiotherapy in patients presenting with metastatic breast cancer

2021 ◽  
pp. 1-6
Author(s):  
Budhi Singh Yadav ◽  
Rubu Sunku ◽  
Divya Dahiya
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Hormone Treatment ◽  
Rank Test ◽  
Factors Affecting ◽  
The Impact ◽  
Regional Treatment

Abstract Background: The impact of loco-regional treatment (LRT) with radiotherapy (RT) in patients presenting with metastatic breast cancer (MBC) has not been widely studied. The aim of this study was to review the treatment outcomes of LRT including RT in patients with MBC. Materials and methods: Patients who presented with MBC were included in this retrospective study. Analysis was undertaken to determine the difference in local disease control, overall survival (OS) and progression-free survival (PFS) with systemic treatment alone, surgery alone, surgery plus RT and RT alone with long-rank test. Multivariate analysis was done, using the cox regression for factors affecting PFS and OS. Results: From 2007 to 2014, data of 257 patients with MBC were collected. Totally, 185 patients received LRT and 72 did not. LRT was surgery plus RT, surgery only and RT only in 113, 47 and 25 patients, respectively. Cytotoxic chemotherapy and hormone therapy were received by 205 and 166 patients, respectively. Median follow-up was 36 months (6–120 months). PFS and OS at 3 years with and without LRT were 31% versus 6% (p < 0·001) and 41% versus 17% (p < 0·001), respectively. PFS at 3 years with surgery plus RT, RT alone and surgery was 40, 33 and 6%, respectively. OS at 3 years with surgery plus RT, RT alone and surgery was 50, 38 and 17%, respectively. Patients without LRT had worse PFS and OS, 6 and 17%, respectively. RT had significant impact on PFS and OS along with chemotherapy and hormone treatment. Conclusion: In patients with MBC, improved local control, PFS and OS were achieved with loco-regional RT. Loco-regional RT along with chemotherapy and hormones were significant factors for PFS and OS irrespective of surgery.

The impact of radiological assessment schedules on progression-free survival in metastatic breast cancer: A systemic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1086-1086
Author(s):  
Dor Reuven Dabush ◽  
Daniel Shepshelovich ◽  
Tzippy Shochat ◽  
Eitan Amir ◽  
Ariadna Tibau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Standard Treatment ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Systemic Review ◽  
Radiological Assessment ◽  
Free Survival ◽  
The Impact

1086 Background: The impact of the interval of radiological assessment on the magnitude of benefit observed in randomized trials (RCTs) in metastatic breast cancer is undefined. Methods: All RCTs investigating anti-neoplastic drugs for metastatic breast cancer published between 2006 and 2019 were identified. Intervals for restaging were categorized as short ( < 9 weeks) or long (≥9 weeks). Hazard ratios (HRs) and 95% confidence intervals for progression-free survival (PFS) and overall-survival (OS) were pooled in a meta-analysis and compared between trials employing short and long restaging intervals assessed as subgroup analyses. Analyses were repeated for pre-specified subgroups according to disease subtype, drug type, whether experimental therapy was added to or replaced standard treatment and whether HR for PFS was < 1 or ≥1. Results: Eighty-nine studies comprising 95 comparisons and 44,901 patients were included. The magnitude of PFS benefit was non-significantly larger in trials which employed short compared to long restaging intervals (HR 0.79 vs. 0.86, p = 0.15). Short restaging interval was associated with significantly higher magnitude of effect on PFS in pre-specified subgroups including non-first line studies (HR 0.78 vs. 0.92, p = 0.04), studies with drugs replacing standard treatment (HR 0.86 vs. 1.04, p = 0.02) and studies performed exclusively in human epidermal growth factor receptor 2 (HER2) positive disease (HR 0.72 vs. 0.90, p = 0.02). Restaging interval was not associated with OS for all included studies (HR 0.92 vs. 0.93, p = 0.66) or for any of the pre-specified subgroups. Conclusions: Shorter restaging intervals are associated with a higher magnitude of effect of PFS, but not OS. Awareness of the impact of the restaging interval on quantification of intermediate endpoints such as PFS is important for the design and interpretation of RCTs.

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