scholarly journals Enzalutamide for the Treatment of Androgen Receptor–Expressing Triple-Negative Breast Cancer

2018 ◽  
Vol 36 (9) ◽  
pp. 884-890 ◽  
Author(s):  
Tiffany A. Traina ◽  
Kathy Miller ◽  
Denise A. Yardley ◽  
Janice Eakle ◽  
Lee S. Schwartzberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
End Points ◽  
Free Survival ◽  
Intent To Treat

Purpose Studies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC. Patients and Methods Tumors were tested for AR with an immunohistochemistry assay optimized for breast cancer; nuclear AR staining > 0% was considered positive. Patients received enzalutamide 160 mg once per day until disease progression. The primary end point was clinical benefit rate (CBR) at 16 weeks. Secondary end points included CBR at 24 weeks, progression-free survival, and safety. End points were analyzed in all enrolled patients (the intent-to-treat [ITT] population) and in patients with one or more postbaseline assessment whose tumor expressed ≥ 10% nuclear AR (the evaluable subgroup). Results Of 118 patients enrolled, 78 were evaluable. CBR at 16 weeks was 25% (95% CI, 17% to 33%) in the ITT population and 33% (95% CI, 23% to 45%) in the evaluable subgroup. Median progression-free survival was 2.9 months (95% CI, 1.9 to 3.7 months) in the ITT population and 3.3 months (95% CI, 1.9 to 4.1 months) in the evaluable subgroup. Median overall survival was 12.7 months (95% CI, 8.5 months to not yet reached) in the ITT population and 17.6 months (95% CI, 11.6 months to not yet reached) in the evaluable subgroup. Fatigue was the only treatment-related grade 3 or higher adverse event with an incidence of > 2%. Conclusion Enzalutamide demonstrated clinical activity and was well tolerated in patients with advanced AR-positive TNBC. Adverse events related to enzalutamide were consistent with its known safety profile. This study supports additional development of enzalutamide in advanced TNBC.

scholarly journals Prediction of Response to Atezolizumab Plus Nab-Paclitaxel in Unresectable Locally Advanced Triple Negative Breast Cancer (TNBC): the ClinicalUsefulness of PD-L1 mRNA Expression in Plasma-Derived Exosomes

2021 ◽  
Author(s):  
Lucrezia Raimondi ◽  
Gian Paolo Spinelli ◽  
Paolo Ciracì ◽  
Filippo Maria Raimondi ◽  
Rachele Lazzeroni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Free Survival ◽  
Non Invasive ◽  
Droplet Pcr ◽  
First Time

Patients diagnosed with unresectable locally advanced Triple Negative Breast Cancer (TNBC) usually have poor outcome for its aggressive clinical behaviour. Atezolizumab plus nanoparticle albumin-bound (nab)-Paclitaxel prolonged progression-free survival (PFS) and overall survival (OS) among patients with unresectable locally advanced TNBC but its use is hampered by the lack of reliable predictors of tumor response. Seventy-seven consecutive patients with unresectable locally advanced TNBC treated with Atezolizumab plus nab-Paclitaxel were studied by blood draws at baseline, 28 days and 56 days after initiation of treatment. Exosomal PD-L1 mRNA in plasma was determined using Bio-Rad QX100 digital droplet PCR system and exoRNeasy kit and objective responses were defined following the RECIST criteria v.1.1. The study evaluates whether PD-L1 mRNA copies per ml in plasma-derived exosomes may predict response to anti-PD-L1 antibodies early in the course of therapy. Our data showed patients with unresectable locally advanced TNBC and higher levels of PD-L1 mRNA expression in plasma-derived exosomes at baseline demonstrated greater response to atezolizumab plus nab-paclitaxel. Furthermore, the levels of mRNA decreased with successful treatment while the copy number increased in patients experiencing disease progression following atezolizumab plus nab-paclitaxel. For the first time, our data showed the usefulness of assessment of exosomal PD-L1 as non-invasive real-time biopsy in patients diagnosed with TNBC suggesting exosomal PD-L1 is significantly associated with outcome and response to Atezolizumab plus nab-Paclitaxel.

Impact of androgen receptor on chemotherapy efficacy in patients with metastatic triple negative breast cancer

2020 ◽  
pp. 80-84
Author(s):  
S.A. Lyalkin ◽  
◽  
L.A. Syvak ◽  
N.O. Verevkina ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Second Line ◽  
Free Survival ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

The objective: was to determine the impact of androgen receptor (AR) expression on the effectiveness of the first and second line chemotherapy in patients with metastatic triple negative breast cancer (mTNBC). Materials and methods. The impact of AR expression on treatment results was evaluated in patients with mTNBC received the first (n=122) and second (n=87) line chemotherapy in open randomized studies. The status of AR was evaluated by immunohistochemistry, AR positive patients were defined as having AR more than 10%. Results. From 116 patients with mTBNC 44 (38%) were AR positive, 72 (62%) – AR negative. Median progression free survival in patients received the first line chemotherapy was 8 months in AR positive and 6 months in AR negative, p=0.27. The incidence of objective tumor response in mTNBC patients received the second line chemotherapy was 71.1% in AR negative and 76.92% in AR positive, p=0.48. Median progression free survival in patients received the second line chemotherapy was 6 months in AR positive and 4 months in AR negative, p=0.0045. Median overall survival in AR positive patients was statistically significantly higher (12 months versus 9 months, р=0.04). Conclusions. Impact of AR expression on progression free and overall survival was proved for mTNBC patients received the second line chemotherapy. Keywords: metastatic triple negative breast cancer, androgen receptor, chemotherapy, progression free survival, overall survival.

Immediate and long-term results of the first line chemotherapy in patients with metastatic triple negative breast cancer. Final analysis of randomized study

2020 ◽  
pp. 75-80
Author(s):  
S.A. Lyalkin ◽  
◽  
L.A. Syvak ◽  
N.O. Verevkina ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Randomized Study ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Group 2 ◽  
Line Chemotherapy ◽  
Group 1

The objective: was to evaluate the efficacy of the first line chemotherapy in patients with metastatic triple negative breast cancer (TNBC). Materials and methods. Open randomized study was performed including 122 patients with metastatic TNBC. The efficacy and safety of the first line chemotherapy of regimens АТ (n=59) – group 1, patients received doxorubicine 60 мг/м2 and paclitaxel 175 мг/м2 and ТР (n=63) – group 2, patients received paclitaxel 175 мг/м2 and carboplatin AUC 5 were evaluated. Results. The median duration of response was 9.5 months (4.5–13.25 months) in patients received AT regimen and 8.5 months (4.7–12.25 months), in TP regimen; no statistically significant differences were observed, р=0.836. The median progression free survival was 7 months (95% CI 5–26 months) in group 1 and 7.5 months (95% CI 6–35 months) in group 2, p=0.85. Both chemotherapy regimens (AT and TP) had mild or moderate toxicity profiles (grade 1 or 2 in most patients). No significant difference in gastrointestinal toxicity was observed. The incidence of grade 3–4 neutropenia was higher in patients of group 2 (TP regimen): 42.8% versus 27% (р<0.05). Conclusions. Both regimens of chemotherapy (AT and TP) are appropriate to use in the first line setting in patients with metastatic TNBC. Key words: metastatic triple negative breast cancer, chemotherapy, progression free survival, chemotherapy toxicity.

Metaplastic progression free survival compared to triple negative breast cancer, a retrospective analysis.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e12552-e12552
Author(s):  
Maryam B. Lustberg ◽  
Amanda Luff ◽  
Gregory S. Young ◽  
Rachel M. Layman ◽  
Ewa Mrozek ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retrospective Analysis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Free Survival

scholarly journals Basal-Like Subgroup is Associated with Younger Age, Increased Expression of Androgen Receptor, and Worse Prognosis, while Non-basal-like Subtype is Associated with Higher BMI in Triple-Negative Breast Cancer Patients

2020 ◽  
Vol 12 (4) ◽  
pp. 349-354
Author(s):  
Ibnu Purwanto ◽  
Didik Setyo Heiyanto ◽  
Ahmad Ghozali ◽  
Irianiwati Widodo ◽  
Iwan Dwiprahasto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Locally Advanced ◽  
Clinicopathologic Feature ◽  
Younger Age ◽  
Depth Analysis ◽  
Worse Prognosis

BACKGROUND: Triple-negative breast cancer (TNBC) represents a heterogenous disease which differ in characteristic, treatment response and prognosis. We aim to perform in-depth analysis on the clinicopathologic feature and the prognostic value of basal-like and non-basal-like TNBC patients in an Indonesian tertiary hospital.METHODS: We retrospectively included patients diagnosed with TNBC between 2014-2017. Clinical variables were collected from medical record. Expression of epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), p53 mutant and androgen receptor (AR) were examined by using immunohistochemistry (IHC).RESULTS: We included 67 subjects, 67.1% were basal-like and the remaining 32.9% were non-basal-like, with mean age of 51 years old, 59.7% subjects had BMI <25 and 40.3% subjects had BMI ≥25; 16.4%, 65.7%, and 17.9% subjects presented with early stage, locally advanced stage, and distant metastasis respectively; T<5 cm was found in 29.9% subjects, while 70.1% subjects had T≥5; 67.2% subjects presented with N-, while 32.8% subjects were N+. The most common histological type was infiltrating ductal (82% of subjects). P53 mutant and AR expressions were positive in 44.8% and 15% subjects, respectively. Basal-like subtype presented with younger age at and had higher expression of AR, while non-basal-like subtype is associated with BMI ≥25 (p<0.05). Basal-like subjects had shorter overall survival (23.9 months (95% CI: 21.9-25.9) vs. 26.1 months (95% CI: 23-29.2).CONCLUSION: Basal-like subtype is associated with worse prognosis, younger age at diagnosis and increased expression of AR, while non-basal-like subtype is associated with higher BMI in Indonesian TNBC.KEYWORDS: TNBC, subtype; basal-like, young age, Indonesia

scholarly journals Real-world effectiveness outcomes in patients diagnosed with metastatic triple-negative breast cancer

2020 ◽  
Author(s):  
Karen E Skinner ◽  
Amin Haiderali ◽  
Min Huang ◽  
Lee S Schwartzberg
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
Unmet Need ◽  
Progression Free Survival ◽  
Free Survival ◽  
Regression Methods ◽  
Kaplan Meier ◽  
Community Oncology

Aim: This study examined treatment patterns and effectiveness outcomes of patients with metastatic triple-negative breast cancer (mTNBC) from US community oncology centers. Materials & methods: Eligible patients were females, aged ≥18 years, diagnosed with mTNBC between 1 January 2010 and 31 January 2016. Kaplan–Meier and Cox regression methods were used. Results: Sample comprised 608 patients with average age of 57.5 years and 505/608 patients (83.1%) received systemic treatment. Overall survival (OS) from first-line treatment found that African–American patients had shorter OS than White (9.3 vs 13.7 months; hazard ratio: 1.35; p = 0.006). Conclusion: More than 15% of women with mTNBC were not treated, indicating a high unmet need. Overall prognosis remains poor, which highlights the opportunity for newer therapies to improve progression-free survival and OS.

Ixabepilone efficacy and tolerability in metastatic breast cancer (MBC) patients in a real-world setting.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13067-e13067
Author(s):  
Tara Hyder ◽  
Margaret Q. Rosenzweig ◽  
Adam Brufsky
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Real World ◽  
Triple Negative ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Real World Setting

e13067 Background: Ixabepilone is a microtubule stabilizing agent that was approved as monotherapy and in combination with capecitabine for the treatment of refractory metastatic or locally advanced breast cancer. With limited options for refractory MBC, especially in triple negative breast cancer (TNBC), ixabepilone has demonstrated an increase in progression free survival (PFS) in randomized control trials. We assess the effectiveness and safety of the drug in a real-world setting. Methods: A large, ongoing clinical database of over 1800 women (1999 to present) was used to identify 91 patients who had received ixabepilone during their treatment course. Clinical outcomes were retrospectively analyzed utilizing descriptive and comparative statistics. Results: Treatment was late in the disease course; median line of treatment was 5.3. At the time of receiving ixabepilone, the patients PFS was 3.5 months with n = 4 patients attaining a PFS > 12 months. Overall survival (OS) was 11.3 months. A subset of patients that had triple negative breast cancer (N = 37) had similar PFS, 3.6 months, and OS, 10.2 months, as the total population. Most common adverse events of any grade were fatigue (37%), nausea (32%), and peripheral sensory neuropathy (28%). Grade 3 or higher anemia was present in 10% of the patients. Conclusions: Ixabepilone has demonstrated efficacy in the treatment of patients with MBC, including the challenging population of TNBC patients in this real-world example. It is also well tolerated. These findings make ixabepilone a reasonable chemotherapeutic agent for refractory MBC and TNBC patients. [Table: see text]

scholarly journals Subgroup analysis of Japanese patients in a Phase 3 study of atezolizumab in advanced triple-negative breast cancer (IMpassion130)

2019 ◽  
Vol 49 (12) ◽  
pp. 1083-1091 ◽  
Author(s):  
Hiroji Iwata ◽  
Kenichi Inoue ◽  
Koji Kaneko ◽  
Yoshinori Ito ◽  
Koichiro Tsugawa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Treatment Withdrawal ◽  
Phase 3 ◽  
Intention To Treat ◽  
Primary Endpoints

Abstract Background In the randomised Phase 3 IMpassion130 trial, atezolizumab combined with nab-paclitaxel (atezo + nab-P) in 902 patients with triple-negative breast cancer (TNBC) showed prolonged progression-free survival (PFS) in both the intention-to-treat (ITT) population and programmed death-ligand 1 (PD-L1)–positive subgroup compared with placebo plus nab-P (plac + nab-P). This study assessed the efficacy and safety of atezo + nab-P in the IMpassion130 Japanese subpopulation. Methods Eligible patients had unresectable locally advanced or metastatic TNBC previously untreated with chemotherapy for metastatic disease. Patients were randomised 1:1 to receive either atezo + nab-P or plac + nab-P. Co-primary endpoints were investigator-assessed PFS and overall survival (ITT population and PD-L1–positive subgroup). These were also assessed in the Japanese subpopulation. Results There were 65 Japanese patients (34 atezo + nab-P; 31 plac + nab-P). The PD-L1–positive subgroup included 25 patients (12 atezo + nab-P; 13 plac + nab-P). Median PFS was 7.4 months (atezo + nab-P) versus 4.6 months (plac + nab-P; hazard ratio [HR], 0.47; 95% CI, 0.25–0.90). In the PD-L1–positive subgroup, median PFS was 10.8 months (atezo + nab-P) versus 3.8 months (plac + nab-P; HR, 0.04; 95% CI, &lt;0.01–0.35). Safety results in the Japanese subgroup were consistent with those in the overall population. The Japanese subgroup had a lower incidence of adverse events leading to treatment withdrawal than the overall population. More patients in the atezo + nab-P arm had neutrophil count decreases and stomatitis than patients in the plac + nab-P arm. Conclusions Atezo + nab-P efficacy in Japanese patients was consistent with the overall IMpassion130 population. No new safety signals were observed, and tolerability was consistent with that of the overall population.

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