scholarly journals Carboplatin-Cyclophosphamide or Paclitaxel without or with Bevacizumab as First-Line Treatment for Metastatic Triple-Negative Breast Cancer (BOOG 2013-01)

Breast Care ◽  
2021 ◽  
pp. 1-9
Author(s):  
Annelot G.J. van Rossum ◽  
Ingrid A.M. Mandjes ◽  
Erik van Werkhoven ◽  
Harm van Tinteren ◽  
A. Elise van Leeuwen-Stok ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
First Line ◽  
Significant Treatment ◽  
Individual Agent ◽  
Efficacy Analysis

<b><i>Background:</i></b> The addition of bevacizumab to chemotherapy conferred a modest progression-free survival (PFS) benefit in metastatic triple-negative breast cancer (mTNBC). However, no overall survival (OS) benefit has been reported. Also, its combination with carboplatin-cyclophosphamide (CC) has never been investigated. <b><i>Methods:</i></b> The Triple-B study is a multicenter, randomized phase IIb trial that aims to prospectively validate predictive biomarkers, including baseline plasma vascular endothelial growth factor receptor-2 (pVEGFR-2), for bevacizumab benefit. mTNBC patients were randomized between CC and paclitaxel (P) without or with bevacizumab (CC ± B or P ± B). Here we report on a preplanned safety and preliminary efficacy analysis after the first 12 patients had been treated with CC+B and on the predictive value of pVEGFR-2. <b><i>Results:</i></b> In 58 patients, the median follow-up was 22.1 months. Toxicity was manageable and consistent with what was known for each agent separately. There was a trend toward a prolonged PFS with bevacizumab compared to chemotherapy only (7.0 vs. 5.2 months; adjusted HR = 0.60; 95% CI 0.33–1.08; <i>p</i> = 0.09), but there was no effect on OS. In this small study, pVEGFR-2 concentration did not predict a bevacizumab PFS benefit. Both the intention-to-treat analysis and the per-protocol analysis did not yield a significant treatment-by-biomarker test for interaction (<i>p</i><sub>interaction</sub> = 0.69). <b><i>Conclusions:</i></b>CC and CC+B are safe first-line regimens for mTNBC and the side effects are consistent with those known for each individual agent. pVEGFR-2 concentration did not predict a bevacizumab PFS benefit.

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.

scholarly journals Immunotherapy in Triple-Negative Breast Cancer: Present and Future

2019 ◽  
Vol 11 (4) ◽  
pp. 259-271 ◽  
Author(s):  
Isaac Kim ◽  
Katherine Sanchez ◽  
Heather L. McArthur ◽  
David Page
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Survival Benefit ◽  
Triple Negative ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Phase Iii ◽  
Breast Cancers ◽  
Effective Treatment Option

Abstract Purpose of Review Immunotherapy is emerging as an effective treatment option for metastatic triple-negative breast cancer. In this review, we summarize clinical data of immunotherapy in triple-negative breast cancer and comment on future directions in the field. Recent Findings IMpassion130 was a phase III trial that demonstrated progression-free survival benefit, and potentially overall survival benefit, of first-line chemotherapy (nab-paclitaxel) plus anti-programmed death ligand 1 (PD-L1) atezolizumab, among PD-L1-positive metastatic triple-negative breast cancers. Studies are ongoing to evaluate other combination therapies with immune checkpoint blockade in TNBC, and to evaluate efficacy in PD-L1-negative tumors and in later lines of therapy. Summary Immunotherapy is now a standard option in the treatment of triple-negative breast cancer. Ongoing trials may expand the degree of clinical benefit. Further work is ongoing to identify novel predictive biomarkers, which in the future may enable a personalized approach of combination immunotherapy.

scholarly journals Clinical Data on Immunotherapy in Breast Cancer

Breast Care ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. 450-469
Author(s):  
Julia Caroline Radosa ◽  
Lisa Stotz ◽  
Carolin Müller ◽  
Askin Canguel Kaya ◽  
Erich-Franz Solomayer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Adoptive Cell Therapy ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
First Line ◽  
Metastatic Setting ◽  
Epidermal Growth

<b><i>Background:</i></b> Breast cancer has traditionally been considered to have a low immunogenic potential compared to other tumor entities. <b><i>Summary:</i></b> The most extensively studied immunotherapeutic agents for breast cancer to date are immune checkpoint inhibitors, with the results of the IMpassion130 trial leading to the approval of atezolizumab plus nab-paclitaxel for first-line treatment of programmed cell death ligand 1-positive, metastatic, triple-negative breast cancer, and studies in earlier stages have yielded promising results. Other immunotherapeutic options being assessed in phases 2 and 3 trials include vaccine-based therapies and treatment with anti-human epidermal growth factor receptor 2 (H-directed immune-linked antibodies) and substances evaluated in early clinical trials as cellular therapies (adoptive cell therapy and chimeric antigen receptor T cells). <b><i>Key Messages:</i></b> Immunotherapy is an emerging modality for the treatment of breast cancer, as evidenced by the plethora of preclinical and clinical concepts and ongoing trials. Early studies established the role of immunotherapeutic agents in the metastatic setting. Ongoing studies will expand our knowledge about the timing of administration, best partners for combination therapy, and predictive biomarkers to guide immunotherapy for breast cancer.

scholarly journals How I treat metastatic triple-negative breast cancer

ESMO Open ◽  
2019 ◽  
Vol 4 (Suppl 2) ◽  
pp. e000504 ◽  
Author(s):  
Rafael Caparica ◽  
Matteo Lambertini ◽  
Evandro de Azambuja
Keyword(s):  
Breast Cancer ◽  
Disease Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Single Agent ◽  
Treatment Algorithm ◽  
Predictive Biomarkers ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Triple-negative breast cancer (TNBC) is associated with a high risk of recurrence and generally a bad prognosis. More than one-third of patients with TNBC will present distant metastases during the course of their disease. Although chemotherapy has been the main treatment option for metastatic TNBC for a long time, this scenario has changed recently with the advent of the polyadenosine diphosphate-ribose polymerase inhibitors (PARPis) for patients harbouring a mutation in the BRCA genes (BRCAmut) and also with the results of immunotherapy in patients with PD-L1-positive tumours. The present manuscript proposes a treatment algorithm for patients with metastatic TNBC based on the currently available, most relevant literature on the topic. For patients with a BRCAmut and able to tolerate chemotherapy, we recommend initiating treatment with platins (carboplatin/cisplatin) and to start PARPis at disease progression. For patients with PD-L1-positive tumours (PD-L1 expression on tumour-infiltrating immune cells ≥1%), we recommend first-line treatment with nab-paclitaxel and atezolizumab, when available. In patients without a BRCA mutation and with PD-L1-negative tumours, we recommend single-agent chemotherapy with taxanes (paclitaxel or docetaxel) as a first-line treatment. In patients with a high disease burden or who are very symptomatic, combinations such as anthracyclines plus cyclophosphamide or platins with taxanes are valid options. Chemotherapy should be maintained until the occurrence of disease progression or limiting toxicities. After progression to first-line chemotherapy, anthracyclines are an option for patients who received taxanes and vice versa. For patients who progressed to taxanes and anthracyclines, or who present contraindications to these agents, fluorouracil/capecitabine, eribulin, gemcitabine, cisplatin/carboplatin, vinorelbine and ixabepilone are alternatives. The treatment of TNBC is constantly evolving, and the inclusion of patients in ongoing trials evaluating new targeted agents, immunotherapy and predictive biomarkers should be encouraged, in an attempt to improve metastatic TNBC treatment outcomes.

scholarly journals Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial

2020 ◽  
Vol 38 (5) ◽  
pp. 423-433 ◽  
Author(s):  
Peter Schmid ◽  
Jacinta Abraham ◽  
Stephen Chan ◽  
Duncan Wheatley ◽  
Adrian Murray Brunt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Akt Inhibitor ◽  
First Line ◽  
Double Blind ◽  
Significance Level ◽  
First Line Therapy ◽  
Line Therapy

PURPOSE The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is frequently activated in triple-negative breast cancer (TNBC). The AKT inhibitor capivasertib has shown preclinical activity in TNBC models, and drug sensitivity has been associated with activation of PI3K or AKT and/or deletions of PTEN. The PAKT trial was designed to evaluate the safety and efficacy of adding capivasertib to paclitaxel as first-line therapy for TNBC. PATIENTS AND METHODS This double-blind, placebo-controlled, randomized phase II trial recruited women with untreated metastatic TNBC. A total of 140 patients were randomly assigned (1:1) to paclitaxel 90 mg/m2 (days 1, 8, 15) with either capivasertib (400 mg twice daily) or placebo (days 2-5, 9-12, 16-19) every 28 days until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), PFS and OS in the subgroup with PIK3CA/ AKT1/ PTEN alterations, tumor response, and safety. RESULTS Median PFS was 5.9 months with capivasertib plus paclitaxel and 4.2 months with placebo plus paclitaxel (hazard ratio [HR], 0.74; 95% CI, 0.50 to 1.08; 1-sided P = .06 [predefined significance level, 1-sided P = .10]). Median OS was 19.1 months with capivasertib plus paclitaxel and 12.6 months with placebo plus paclitaxel (HR, 0.61; 95% CI, 0.37 to 0.99; 2-sided P = .04). In patients with PIK3CA/ AKT1/ PTEN-altered tumors (n = 28), median PFS was 9.3 months with capivasertib plus paclitaxel and 3.7 months with placebo plus paclitaxel (HR, 0.30; 95% CI, 0.11 to 0.79; 2-sided P = .01). The most common grade ≥ 3 adverse events in those treated with capivasertib plus paclitaxel versus placebo plus paclitaxel, respectively, were diarrhea (13% v 1%), infection (4% v 1%), neutropenia (3% v 3%), rash (4% v 0%), and fatigue (4% v 0%). CONCLUSION Addition of the AKT inhibitor capivasertib to first-line paclitaxel therapy for TNBC resulted in significantly longer PFS and OS. Benefits were more pronounced in patients with PIK3CA/ AKT1/ PTEN-altered tumors. Capivasertib warrants further investigation for treatment of TNBC.

scholarly journals Relationship About KI67 and Chemotherapy Regimens About Progression Free Survival in Triple Negative Breast Cancer

2021 ◽  
pp. 1-5
Author(s):  
Guzmán-Casta Jordi
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Public Institution ◽  
First Line ◽  
Free Survival ◽  
Relationship Of ◽  
The Relationship

Objective: To determine the experience in a public institution (Hospital General de México) the relationship of KI67% and chemotherapy regimens about the progression free survival. Design: It is a retrospective study in which a total of 64 patients with a 36-month follow-up were evaluated, evaluating the percentage of KI67 and the chemotherapy regimens, which were AC+TXL vs CBP/TXL+AC. Results: A progression-free survival of 11.9 months was demonstrated in the patients who started with the CBP / TXL-based chemotherapy regimen and sequentially AC versus the 9.7 months achieved with the conventional ACX4 scheme and later add Carboplatin and Paclitaxel, and a Overall in both arms of 10.8 months, the patients who demonstrated the presence of a higher KI67 demonstrated increased progression-free survival compared to those with a low KI67, and with an unexpected surrogate that despite being few patients, those who showed higher levels of Progesterone had a lower survival compared to percentages of 5% or negative. Conclusions: Despite the fact that the first-line scheme for triple negative breast cancer was sequential and that the sample was only 64 patients, it was shown that adding carboplatin in the first line together with Paclitaxel in patients with high KI67 and without or with a minimal percentage of progresterone receptors increases Progression Free Survival.

MiRNAs-181a/b as Predictive biomarkers for olaparib sensitivity in triple-negative breast cancer cells.

2017 ◽  
Vol 12 (1) ◽  
pp. 221-229
Author(s):  
Abeer M. Ashmawy ◽  
Mona A. Sheta ◽  
Faten Zahran ◽  
Abdel Hady A. Abdel Wahab
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Predictive Biomarkers

25 Line of therapy adjustment in a patient with advanced triple-negative breast cancer (TNBC) by using personalized ctDNA test for treatment response monitoring

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A24-A24
Author(s):  
Georges Azzi ◽  
Shifra Krinshpun ◽  
Antony Tin ◽  
Allyson Malashevich ◽  
Meenakshi Malhotra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ct Scan ◽  
Treatment Response ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Bilateral Mastectomy ◽  
First Line ◽  
Pet Ct ◽  
Line Of Therapy ◽  
Pet Ct Scan

BackgroundTriple negative breast cancer (TNBC) is an aggressive form of breast cancer that is most difficult to treat due to the absence of hormone/growth factor receptors.1 2 Metastatic TNBC (mTNBC) is particularly challenging, given the limited efficacy and duration of response to chemotherapy.3 The repertoire of therapeutic options for mTNBC patients continues to increase with chemotherapeutic and immuno oncology based treatments and now includes sacituzumab govitecan, a novel antibody-chemotherapy conjugate.4MethodsHere we present a case study of a 40-year-old female who on biopsy of her left breast mass was diagnosed with TNBC. The patient underwent neoadjuvant chemotherapy with weekly administration of paclitaxel and carboplatin followed by dose-dense doxorubicin with cyclophosphamide. Following one-month, the patient underwent bilateral mastectomy, showing pathological staging ypT2 pN0. The patient underwent periodic radiological imaging along with the assessment of circulating tumor DNA in blood using a personalized and tumor-informed multiplex PCR, next-generation sequencing assay (Signatera bespoke, mPCR NGS assay) to identify the minimal residual disease (MRD) and treatment response.ResultsAfter surgery, MRD assessment revealed ctDNA positive status (0.41 MTM/mL) prompting PET/CT scan that revealed liver metastasis. Continued ctDNA monitoring showed continuous increase in ctDNA concentration (287.09 MTM/mL). Separate analyses indicated MSI-high and PD-L1 positive tumor status, leading to the initiation of the first line of therapy (nab-paclitaxel and Atezolizumab), which resulted in ctDNA decline (39.62 MTM/ml). Weekly ctDNA monitoring noted a rapid increase a month later (178 MTM/ml to 833.69 MTM/ml) within a 2-week interval, which corresponded to disease progression on imaging. Given non-responsiveness with the first-line therapy, the patient was initiated with sacituzumab govitecan. Following this, a rapid decline in the ctDNA level was observed within a week (364.07 MTM/mL) with a downward trend to 73.03 MTM/ml by two weeks. An interval PET/CT scan showed a mixed response. Continued monitoring of ctDNA demonstrated ctDNA levels <5MTM/mL for a period of two months before serially rising again (to 89.27 MTM/ml). PET-CT ordered in response to increasing ctDNA levels confirmed progression involving hepatic and lung lesions. A new line of therapy with nivolumab and ipilimumab was subsequently initiated.ConclusionsSerial monitoring of ctDNA enables early detection of therapy resistance and provides a rationale for treatment change/optimization/discontinuation as compared to periodic imaging that is currently the standard of care. The ease and convenience of using ctDNA-based testing as frequently as every week clearly identified earlier non-responsiveness to IO and also identified earlier acquired resistance to antibody-drug conjugate, enabling a prompt switch to alternative therapy.Ethics ApprovalN/AConsentN/AReferencesAnders C, Carey LA. Understanding and treating triple-negative breast cancer. Oncology (Williston Park). 2008;22(11):1233–1243.Mehanna J, Haddad FG, Eid R, Lambertini M, Kourie HR. Triple-negative breast cancer: current perspective on the evolving therapeutic landscape. Int J Womens Health2019;11:431–437. Published 2019 Jul 31. doi:10.2147/IJWH.S178349Treatment of Triple-negative Breast Cancer. American Cancer Society Website. Updated 2020. Accessed August 10, 2020. https://www.cancer.org/cancer/breast-cancer/treatment/treatment-of-triple-negative.htmlBardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med 2019;380(8):741–751. doi:10.1056/NEJMoa1814213

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