scholarly journals Use of HER2-Directed Therapy in Metastatic Breast Cancer and How Community Physicians Collaborate to Improve Care

2020 ◽  
Vol 9 (6) ◽  
pp. 1984 ◽  
Author(s):  
Joanne E. Mortimer ◽  
Laura Kruper ◽  
Mary Cianfrocca ◽  
Sayeh Lavasani ◽  
Sariah Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Research Network ◽  
Her2 Positive ◽  
Community Partners ◽  
Significant Prolongation ◽  
Positive Breast Cancer

The development of new HER2-directed therapies has resulted in a significant prolongation of survival for women with metastatic HER2-positive breast cancer. Discoveries in the laboratory inform clinical trials which are the basis for improving the standard of care and are also the backbone for quality improvement. Clinical trials can be completed more rapidly by expanding trial enrollment to community sites. In this article we review some of the challenges in treating metastatic breast cancer with HER2-directed therapies and our strategies for incorporating our community partners into the research network.

scholarly journals Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takahiro Nakayama ◽  
Tetsuhiro Yoshinami ◽  
Hiroyuki Yasojima ◽  
Nobuyoshi Kittaka ◽  
Masato Takahashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Observational Study ◽  
Real World ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
The Real ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Abstract Background Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post–T-DM1 treatments is currently lacking. We evaluated the effectiveness of post–T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer. Methods In this multicenter, retrospective, observational study, real-world clinical data of female patients with HER2-positive breast cancer who had a history of T-DM1 treatment were consecutively collected from five sites in Japan. We investigated the effectiveness of post–T-DM1 therapy by evaluating the real-world progression-free survival (rwPFS), time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Tumor response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines. Subgroup and exploratory analyses according to background factors were also undertaken. Results Of the 205 patients who received T-DM1 treatment between 1 January 2014 and 31 December 2018, 128 were included in this study. Among the 128 patients analyzed, 105 (82%) patients received anti-HER2 therapy and 23 (18%) patients received regimens without anti-HER2 therapy. Median (95% confidence interval [CI]) rwPFS, TTF, and OS were 5.7 (4.8–6.9) months, 5.6 (4.6–6.4) months, and 22.8 (18.2–32.4) months, respectively. CBR and ORR (95% CI) were 48% (38.8–56.7) and 23% (15.1–31.4), respectively. Cox-regression analysis showed that an ECOG PS score of 0, a HER2 immunohistochemistry score of 3+, recurrent type, ≥12 month duration of T-DM1 therapy, and anti-HER2 therapy were independent variables for rwPFS. An exploratory subgroup analysis of regimens after T-DM1 showed that those with anti-HER2 therapy had a median rwPFS of 6.3 and those without anti-HER2 therapy had a median rwPFS of 4.8 months. Conclusions In the real-world setting in Japan, several post–T-DM1 regimens for patients with unresectable and/or metastatic HER2-positive breast cancer, including continuation of anti-HER2 therapy, showed some effectiveness; however, this effectiveness was insufficient. Novel therapeutic options are still needed for further improvement of PFS and OS in later treatment settings. Trial registration UMIN000038296; registered on 15 October 2019.

Real-World Evidence: A Comparison of the Australian Herceptin Program and Clinical Trials of Trastuzumab for HER2-Positive Metastatic Breast Cancer

2016 ◽  
Vol 34 (10) ◽  
pp. 1039-1050 ◽  
Author(s):  
Bonny Parkinson ◽  
Rosalie Viney ◽  
Marion Haas ◽  
Stephen Goodall ◽  
Preeyaporn Srasuebkul ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Real World Evidence

scholarly journals Trastuzumab for HER2-Positive Metastatic Breast Cancer: Clinical and Economic Considerations

2012 ◽  
Vol 6 ◽  
pp. CMO.S6460 ◽  
Author(s):  
Alwin Jeyakumar ◽  
Tallal Younis
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Drug Acquisition ◽  
Metastatic Breast ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Humanized Monoclonal Antibody ◽  
Clinical Benefits ◽  
Cellular Domain

Trastuzumab is a recombinant humanized monoclonal antibody that selectively targets the extra-cellular domain of the HER2 receptor. It was approved by the FDA in September 1998 as the first targeted therapy for HER2-positive metastatic breast cancer, and has since led to significant improvements in the overall prognosis for patients with HER2-positive metastatic disease. The favourable benefit/risk profile associated with palliative trastuzumab has been demonstrated in a number of clinical trials that examined trastusumab as monotherapy or in combination with chemotherapy, endocrine therapy and other HER2 targeted agents. The clinical benefits of trastuzumab, however should also be examined within the context of its significant drug acquisition costs. This review highlights the significant findings from the landmark clinical trials of trastuzumab for metastatic HER2-positive breast cancer, and the potential “value for money” associated with its use in clinical practice.

scholarly journals Long term continuous Trastuzumab use for HER2-positive advanced breast cancer

2020 ◽  
Vol 6 (5) ◽  
Author(s):  
Haider Y. Shukur
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Loading Dose ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Trastuzumab Therapy ◽  
Locally Recurrent ◽  
Positive Breast Cancer

Objectives: Trastuzumab is the standard of care for locally advanced / metastatic her2-positive breast cancer. However, most of these patients will progress within 12 months of trastuzumab therapy. In contrast, there is a paucity of data available on the long-term treatment of patients with Trastuzumab. Our study was conducted to report efficacy and safety data for patients with locally recurrent / metastatic her2-positive breast cancer who received long-term therapy with Trastuzumab (≥5 years). Methods: This study was a prospective single-arm study of continuous Trastuzumab in patients who were histologically her2-positive and radiologically confirmed inoperable locally recurrent or metastatic breast cancer after complete one year of Trastuzumab plus chemotherapy (in hormone negative/hormone resistance) treatment then continuous Trastuzumab alone , or with hormone therapy (in sensitive hormone positive) without progression [complete or partial response or stable disease].  A total of 50 inoperable local recurrent and metastatic breast cancer  patients were treated with continuous intravenous Trastuzumab therapy administered according to the standard Trastuzumab every 3-weeks (8 mg/kg loading dose followed by 3-weekly 6  mg/kg maintenance doses starting 3 weeks after the loading dose) schedule, from January 2014 to January 2019 at the Najaf Cancer Clinic (NCC). Results: All 50 patients were evaluated with CR occur only in 20% (10/50) with an OAR of 50% (25/50). The cardiac status of these patients remained stable over time for the majority of patients with no marked changes in LVEF%. No treatment-related death was observed. The median OS and median PFS is 61 months and 20 months, respectively. Conclusion: In her2-positive recurrent and metastatic breast cancer patients, who initially respond to palliative treatment with trastuzumab, continuous trastuzumab can achieve a long-term tumor remission of several years and had significantly improved survival with tolerated and acceptable adverse events.

scholarly journals New Therapeutic Strategies in Advanced Nonoperable or Metastatic HER2-positive Breast Cancer

2021 ◽  
Vol 81 (06) ◽  
pp. 666-678
Author(s):  
Diana Lüftner ◽  
Matthias Peipp
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Antibody Engineering ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
The Us ◽  
Positive Breast Cancer

AbstractDespite therapeutic gains in the treatment of HER2-positive (HER2: human epidermal growth factor receptor 2) advanced/metastatic breast cancer, there remains an urgent need for more effective treatment options. At present, there is no definitive approved standard therapy beyond second-line treatment. One of the major challenges is overcoming treatment resistance. Depending on the underlying resistance mechanism, different strategies are being pursued for new innovative treatment concepts in HER2-positive breast cancer. Specifically designed antibodies for targeted therapy are one important focus to successfully meet these challenges. Trastuzumab deruxtecan (T-DXd, DS-8201a), an optimised antibody drug conjugate (ADC) is in clinical trials, showing promising outcomes in patients with advanced, nonoperable or metastatic HER2-positive breast cancer who had already undergone intensive prior treatment. Based on this data, T-DXd has already been approved in the US and Japan for HER2-positive advanced nonoperable and metastatic breast cancer – in the US after at least two prior anti-HER2 targeted treatment lines and in Japan after prior chemotherapy. T-DXd represents successful “antibody engineering”. Since the beginning of the year, T-DXd has also been approved in Europe as monotherapy for inoperable or metastatic HER2-positive breast cancer in patients who are pretreated with at least two anti-HER2 directed therapies. This paper presents strategies for improving treatment options in advanced nonoperable and metastatic HER2-positive breast cancer, with the development of T-DXd as an example.

scholarly journals Pertuzumab and trastuzumab: the rationale way to synergy

2016 ◽  
Vol 88 (suppl 1) ◽  
pp. 565-577 ◽  
Author(s):  
SANDRINE RICHARD ◽  
FRÉDÉRIC SELLE ◽  
JEAN-PIERRE LOTZ ◽  
AHMED KHALIL ◽  
JOSEPH GLIGOROV ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Synergistic Activity ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Protein ◽  
New Class ◽  
Accelerated Approval

ABSTRACT It has now been 15 years since the HER2-targeted monoclonal antibody trastuzumab was introduced in clinical and revolutionized the treatment of HER2-positive breast cancer patients. Despite this achievement, most patients with HER2-positive metastatic breast cancer still show progression of their disease, highlighting the need for new therapies. The continuous interest in novel targeted agents led to the development of pertuzumab, the first in a new class of agents, the HER dimerization inhibitors. Pertuzumab is a novel recombinant humanized antibody directed against extracellular domain II of HER2 protein that is required for the heterodimerization of HER2 with other HER receptors, leading to the activation of downstream signalling pathways. Pertuzumab combined with trastuzumab plus docetaxel was approved for the first-line treatment of patients with HER2-positive metastatic breast cancer and is currently used as a standard of care in this indication. In the neoadjuvant setting, the drug was granted FDA-accelerated approval in 2013. Pertuzumab is also being evaluated in the adjuvant setting. The potential of pertuzumab relies in the dual complete blockade of the HER2/3 axis when administered with trastuzumab. This paper synthetises preclinical and clinical data on pertuzumab and highlights the mechanisms underlying the synergistic activity of the combination pertuzumab-trastuzumab which are essentially due to their complementary mode of action.

Trastuzumab emtansine (T-DM1) and ribociclib, an oral inhibitor of cyclin dependent kinase 4 and 6 (CDK 4/6), for patients with metastatic HER2-positive breast cancer: Phase 1b clinical trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1106-TPS1106 ◽  
Author(s):  
Laura Spring ◽  
Shom Goel ◽  
Dejan Juric ◽  
Steven J. Isakoff ◽  
Stephanie Haddad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Metastatic Breast ◽  
Clinical Activity ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

TPS1106 Background: Despite the availability of multiple effective therapies, most patients with metastatic HER2-positive breast cancer will experience disease progression and death. While traditionally the focus has been targeting the HER receptor family itself, combinations involving targets downstream of the HER2 pathway, particularly CDK 4/6, could potentially enhance therapeutic efficacy. In pre-clinical models of acquired resistance to HER2-targeted therapies, inhibition of CDK4/6 has been shown to result in tumor inhibition. Trial Design: This phase Ib, single arm, open-label clinical trialis investigating the combination of Trastuzumab emtansine (T-DM1) and the CDK4/6 inhibitor, ribociclib (LEE011). Eligible patients include patients age ≥ 18 years with HER2-positive metastatic breast cancer. Prior treatment with at least one regimen containing trastuzumab and a taxane is required. Ribociclib is given orally for two weeks of a 21-day cycle (days 8-21), with T-DM1 given at standard dose every 3 weeks on day 1. Trial Objectives: 1. To estimate the MTD and/or RP2D of ribociclib in combination with T-DM1. 2. To assess the safety and tolerability of ribociclib in combination with T-DM1. 3. To explore the clinical activity of T-DM1 and ribociclib in HER2-positive metastatic breast cancer. 4. To assess potential biomarkers of response to ribociclib in combination with T-DM1. Statistical Methods: A standard 3+3 dose escalation design is being used to evaluate various doses of ribociclib in combination with T-DM1 to determine the maximum tolerated dose (MTD) and/or recommended phase-2 dose (RP2D). Once MTD/RP2D is determined there will be a dose-expansion cohort (N = l5) to confirm the safety profile and evaluate preliminary evidence of efficacy, including objective response rate (ORR) by RECIST 1.1 and progression-free survival (PFS). Clinical trial information: NCT02657343.

scholarly journals Pharmacotherapeutics of capecitabine and trastuzumab in the treatment of metastatic breast cancer

2020 ◽  
Vol 29 (3) ◽  
pp. S4-S9 ◽  
Author(s):  
Sarah McCauley ◽  
Gillian Carter ◽  
Maggie Bennett ◽  
Oonagh McNally ◽  
Katherine MA Rogers
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Critical Appraisal ◽  
Metastatic Breast ◽  
Critical Discussion ◽  
Combination Regimen ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Incurable Disease ◽  
Positive Breast Cancer

Metastatic HER2-positive breast cancer is an incurable disease with a poor prognosis. This article presents a critical appraisal of two treatments commonly used in the treatment of metastatic HER2-positive breast cancer: the oral chemotherapy drug, capecitabine, and the monoclonal antibody, trastuzumab. What follows is a critical discussion of the pharmacotherapeutics of capecitabine and trastuzumab, which considers their use both as single agents and as a combination regimen in the treatment of metastatic breast cancer. The implications of side effects of these drugs are discussed, both individually and in combination, as are the challenges these bring to the prescriber. The article evaluates the use of these agents and concludes that the combination of capecitabine and trastuzumab is an attractive treatment option for patients and for the prescriber.

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