Impact of routine tumor genotyping on enrollment in targeted therapy trials for metastatic breast cancer (MBC): 4-year review.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 145-145
Author(s):  
Aditya Bardia ◽  
Dejan Juric ◽  
Steven J. Isakoff ◽  
Darrell R. Borger ◽  
Dora Dias-Santagata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Driver Mutations ◽  
Oncogenic Driver ◽  
Her 2 ◽  
Clinical Trial Enrollment ◽  
Tumor Genotyping

145 Background: Major barriers to enrollment in therapeutic clinical trials (<5% in United States) include low response rate in phase I/II trials and low enthusiasm among oncologists. Stratified clinical trial enrollment based on molecular profiling of tumors represents a potential paradigm shift in drug development. Here we assess the clinical utility of tumor genotyping for identification of oncogenic driver mutations and enrollment in therapeutic clinical trials for patients with metastatic breast cancer (MBC). Methods: A robust, high-throughput tumor genotyping assay (Snapshot), was developed at our institution to assess for presence of potentially actionable oncogenic driver mutations (15 genes, 130 mutations) using DNA derived from formalin-fixed, paraffin-embedded (FFPE) tissue. The tumor genotyping assay was ordered by oncologists in clinic for patients with MBC. Relevant clinical information was gathered from chart reviews. Descriptive statistics were used for analysis. Results: From 2009-2012, 347 breast tumors were prospectively genotyped in the study population (median age = 50, range 27-90). The common oncogenic mutations were seen in all breast cancer subtypes. PIK3CA mutation (23.3%) was the most common mutation detected overall, albeit at varying frequency in tumor subtypes: HR+ (29.1%, N= 210), HER-2+ (21.5%, N = 65), TN (8.3%, N = 72). Unanticipated mutations in KRAS, BRAF, IDH, and HER-2 were also discovered. Clinical genotyping helped identify breast origin for carcinomas of unknown primary and revealed changes in mutation profile in metastatic tumors from primary tumors. Enrollment in clinical trials for MBC almost quadrupled from 2005-2008 to 2009-2012, with approximately one-third of patients undergoing tumor genotype testing enrolling in clinical trials, particularly phase-I genotype-directed targeted therapy, such as PI3K inhibitor, Akt inhibitor, and PI3K/MEK inhibitor combination. Conclusions: Routine tumor genotyping can be successfully incorporated into clinical practice to significantly enhance therapeutic clinical trial enrollment and potentially accelerate development of genotype-directed targeted therapies for MBC.

Impact of routine tumor genotyping on enrollment in targeted therapy trials for metastatic breast cancer (MBC): 4-year review.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 533-533
Author(s):  
Aditya Bardia ◽  
Steven J. Isakoff ◽  
Dejan Juric ◽  
Darrell R. Borger ◽  
Dora Dias-Santagata ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Phase 1 ◽  
Driver Mutations ◽  
Genotyping Assay ◽  
Oncogenic Driver ◽  
Her 2 ◽  
Clinical Trial Enrollment ◽  
Tumor Genotyping

533 Background: Major barriers to enrollment in therapeutic clinical trials (<5% in United States) include low response rate in phase 1/2 trials and low enthusiasm among oncologists. Stratified clinical trial enrollment based on molecular profiling of tumors represents a potential paradigm shift in drug development. Here we assess the clinical utility of tumor genotyping for identification of oncogenic driver mutations and enrollment in therapeutic clinical trials for patients with MBC. Methods: A robust, high-throughput tumor genotyping assay (Snapshot), was developed at our institution to assess for presence of potentially actionable oncogenic driver mutations (15 genes, 130 mutations) using DNA derived from formalin-fixed, paraffin-embedded (FFPE) tissue. The tumor genotyping assay was ordered by oncologists in clinic for patients with MBC. Relevant clinical information was gathered from chart reviews. Descriptive statistics were used for analysis. Results: From 2009-2012, 347 breast tumors were prospectively genotyped in the study population (median age = 50, range 27-90). PIK3CA mutation (23.3%) was the most common mutation detected overall, albeit at varying frequency in tumor subtypes: HR+ (29.1%, N= 210), HER-2+ (21.5%, N = 65), TN (8.3%, N = 72). Unanticipated mutations in KRAS, BRAF, IDH, and HER-2 were also discovered. Clinical genotyping helped identify breast origin for carcinomas of unknown primary and revealed changes in mutation profile in metastatic tumors from primary tumors. Enrollment in clinical trials for MBC almost quadrupled from 2005-2008 to 2009-2012, with 35.5% of patients undergoing tumor genotype testing enrolling in trials, particularly phase-1 genotype-directed targeted therapy, such as PI3K inhibitors, Akt inhibitors, and combined PI3K/MEK inhibitors. Conclusions: Routine tumor genotyping can be successfully incorporated into clinical practice to significantly enhance therapeutic clinical trial enrollment and potentially accelerate development of genotype-directed targeted therapies for MBC.

scholarly journals Enrollment of Older Metastatic Breast Cancer Patients in First Line Clinical Trials: 9-Year Experience of the Large-Scale Real-Life Multicenter French ESME Cohort

2021 ◽  
Author(s):  
Michael Bringuier ◽  
Matthieu Carton ◽  
christelle Levy ◽  
Anne Patsouris ◽  
David Pasquier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Large Scale ◽  
Multivariable Analysis ◽  
Real Life ◽  
Metastatic Breast ◽  
First Line

Abstract Purpose: Older cancer patients are underrepresented in clinical trials. We aimed to understand barriers to clinical trial recruitment in women aged 70 years old (yo) or over with metastatic breast cancer (MBC).Methods: We used the national Epidemio-Strategy and Medical Economics MBC Data Platform, a French multi-center real life database. We selected MBC women over 70yo, without central nervous system metastases, with at least one line of systemic treatment, between January 1st, 2008 and December 31st, 2016, and had no other cancer in the 5 years before MBC. The primary objective was to evaluate the proportion of patients enrolled in clinical trials according to their age. Secondary objective was to identify variables associated with enrollment.Results: 5552 women were aged ≥ 70 (median 74yo; IQR72-77). 14611 were less than 70. Of the older ones, 239 (4%) were enrolled in a clinical trial during first line of treatment, compared with 1529 (10.5%) for younger ones. Multivariable analysis of variables predicting for enrollment during first line of treatment in older patients were younger age (OR 0.50 [95%CI; 0.33-0.76] for the 80-85yo class; OR 0.17 [95%CI; 0.06-0.39] for the 85yo and more class), good ECOG Performance Status (PS 0-1) (OR 0.15 [95%CI; 0.08-0.27] for the PS 2-4 class), HER2+ disease (OR 1.78 [95%CI; 1.27-2.48]), type of treatment (chemotherapy/targeted therapy/immunotherapy OR 5.01 [95%CI; 3.13-8.18]), and period (OR 1.65 [95%CI; 1.22–2.26] for 2012-2016, compared to 2008-2011).Conclusions: In this large database, few older MBC patients were enrolled in a trial compared with younger ones.

scholarly journals A systematic review and meta-analysis of nab-paclitaxel mono-chemotherapy for metastatic breast cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Haili Lu ◽  
Siluo Zha ◽  
Wei Zhang ◽  
Qiang Wang ◽  
Daozhen Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
First Line ◽  
Line Therapy ◽  
Her 2 ◽  
Meta Regression

Abstract Background Although various clinical trials and real-life studies have tried to explore the value of nab-paclitaxel mono-chemotherapy for metastatic breast cancer (MBC), the safety and efficacy of nab-paclitaxel remain unclear which need to be systematically evaluated. Methods Electronic searches for prospective clinical trials evaluating nab-paclitaxel monotherapy for MBC were performed. Requisite data were extracted, integrated and analysed from the included studies according to the different study designs using systematic review and meta-analysis. Meta-regression and subgroup analysis were further performed to explore the potential risk factors affecting each individual outcome of interest following nab-paclitaxel monotherapy. Results Twenty-two studies with 3287 MBC patients were included. A total of 1685 MBC patients received nab-paclitaxel as first-line therapy, 640 patients as further-line therapy, and 962 patients as mixed-line therapy. A total of 1966 MBC patients (60.40%) received nab-paclitaxel weekly, 1190 patients (36.56%) received nab-paclitaxel triweekly and 99 patients (3.04%) received nab-paclitaxel biweekly. The overall incidence rates of all-grade neutropenia, leukopenia, peripheral sensory neuropathy, and fatigue were 52% (95% CI, 38–66%, I2 = 98.97%), 58% (95% CI, 43–73%, I2 = 97.72%), 58% (95% CI, 48–68%, I2 = 97.17%), and 49% (95% CI, 41–56%, I2 = 94.39%), respectively. The overall response rate (ORR) was 40% (95% CI, 35–45%, I2 = 98.97%), and the clinical benefit rate (CBR) was 66% (95% CI, 59–73%, I2 = 98.97%) following nab-paclitaxel monotherapy. The median progression-free survival (PFS) was 7.64 months (95% CI, 6.89–8.40 months, I2 = 92.3%), and the median overall survival (OS) was 24.51 months (95% CI, 21.25–27.78 months, I2 = 92.7%). Treatment line, human epidermal growth factor receptor-2(Her-2)-negative status and dosage were found to be sources of heterogeneity among the included studies. According to the meta-regression and subgroup analysis, grade 3/4 neutropenia occurred less frequently in Her-2-negative patients than in the entire population (P = 0.046). Patients who received first-line nab-paclitaxel monotherapy showed a higher ORR (P = 0.006) and longer PFS (P = 0.045). Efficacy outcomes were not affected by the administration schedule. However, within the same schedule, patients appeared to have a superior ORR (P = 0.044) and longer PFS (P = 0.03) with an increasing dosage of nab-paclitaxel administered. Conclusions The benefits brought by nab-paclitaxel mono-chemotherapy in the treatment of MBC are considerable while the harm is generally manageable. Further study and validation are needed to figure out the roles which the dosage, schedule and other factors play actually in nab-paclitaxel chemotherapy.

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