scholarly journals Pertuzumab in Combination with Trastuzumab and Chemotherapy in the Treatment of HER2-Positive Metastatic Breast Cancer: Safety, Efficacy, and Progression Free Survival

2014 ◽  
Vol 8 ◽  
pp. BCBCR.S9032 ◽  
Author(s):  
Joseph J. Maly ◽  
Erin R. Macrae
Keyword(s):  
Breast Cancer ◽  
Kinase Inhibitors ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Preclinical Research ◽  
Her2 Positive ◽  
Cancer Management ◽  
Improved Outcomes ◽  
Breast Cancer Management ◽  
Computer Based

Tyrosine kinase inhibitors have revolutionized the oncology community and were pioneered by the use in HER2-targeted therapies. Improved outcomes were seen with the advent of trastuzumab, leading investigators to develop newer agents to target the HER2 pathway such as the novel monoclonal antibody pertuzumab. In this paper, we describe the attributes of pertuzumab including: mechanism of action, pharmacokinetics and metabolism, safety/cardiotoxicity, drug interactions, efficacy, and role in HER2-positive breast cancer management. Newly reviewed here versus previously published reviews on pertuzumab oriented therapy are data of pertuzumab monotherapy as it is used in combination with other anti-HER2 agents derived from preclinical research and ongoing clinical trials. Materials and Methods A computer based literature search was carried out using PubMed data reported at international meetings (ASCO) up to September 2013 were included.

scholarly journals ASCO 2019: highlights in HER2-positive metastatic breast cancer

2019 ◽  
Vol 12 (4) ◽  
pp. 308-311 ◽  
Author(s):  
Rupert Bartsch ◽  
Elisabeth Bergen
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Kinase Inhibitors ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
High Rate ◽  
Phase Iii ◽  
Her2 Positive ◽  
Line Setting

Summary At the 2019 ASCO (American Society of Clinical Oncology) Annual Meeting, several interesting trial results were presented in the field of HER2-positive metastatic breast cancer. The end-of-study analysis of the pivotal CLEOPATRA trial indicated an overall survival of 57.1 months in patients receiving pertuzumab in addition to trastuzumab and docetaxel in the first-line setting. SOPHIA was the first phase III trial comparing the Fc-engineered antibody margetuximab plus chemotherapy by physician’s choice with trastuzumab plus chemotherapy in heavily pretreated patients; the novel antibody yielded a statistically significant albeit short prolongation of progression-free survival (PFS) over standard treatment. The phase III NALA trial compared the second-generation tyrosine-kinase inhibitors neratinib with lapatinib; both drugs were combined with capecitabine. In this study a clinically meaningful prolongation of PFS by 2.2 months was observed. In addition, the time to intervention for brain metastases was prolonged in the neratinib group and the cumulative incidence of brain metastases was lower as well. On the downside a high rate of grade 2 and 3 diarrhoea was observed.

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

scholarly journals Management of Breast Cancer in Nepal

2009 ◽  
Vol 48 (175) ◽  
Author(s):  
Yogendra P Singh ◽  
P Sayami
Keyword(s):  
Breast Cancer ◽  
Early Detection ◽  
Cancer Education ◽  
Tumor Biology ◽  
Metastatic Breast ◽  
Premenopausal Women ◽  
Clinical Breast Examination ◽  
Cancer Management ◽  
Breast Cancer Management ◽  
Clinical Breast

Breast cancer is the second most common malignancy among women in Nepal. It is more commonin young premenopausal women. Breast cancer continues to increase in incidence due to lifestylechanges in Nepalese women despite constant remarkable development in the management of thisdisease over the past three decades. Breast cancer was diagnosed solely clinically and surgery wasthe only treatment option until fi fty years ago. Multidisciplinary approach has been adopted fordiagnosis and treatment of breast cancer in Nepal. Imaging is required for the diagnosis, appropriatetreatment decision and proper follow up. Treatment modality depends upon the extent of thedisease and tumor biology. However, there is a strong need for standard guidelines for the propermanagement of breast cancer in Nepal so that surgeries, chemotherapy, hormone therapy andradiotherapy are standardized in the country. Palliative care has been initiated to provide to somepatients with metastatic breast cancer recently.The breast cancer management in Nepal is a little different when compared with the centers in thedeveloped countries. The reasons are socioeconomic status, lack of education and lack of facilities.Although cancer care is on the rise in Nepal, the optimal facility for centers managing breast cancerhas to be improved signifi cantly.Cancer education, screening and early detection are the keyelements to infl uence the diagnosis, treatment and prognosis of breast cancer in Nepal. Breast cancerawareness and clinical breast examination are important tools for early detection in our resourcelimited context. Breast cancer can be cured in majority of the cases if diagnosed in early stages.This review will focus on relevant patient data along with future recommendation regarding breastcancer treatment in Nepal.Key Words: Breast cancer, cancer education, chemotherapy, imaging, radiotherapy, surgery

Suggested modifications in the management of breast cancer patients in the era of COVID-19 pandemic: a web-based survey. (Preprint)

2021 ◽  
Author(s):  
Shereef Elsamany ◽  
Mohamed Elbaiomy ◽  
Ahmed Zeeneldin ◽  
Emad Tashkandi ◽  
Fayza Hassanin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
United Arab Emirates ◽  
Hormonal Therapy ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Web Based ◽  
Cancer Management ◽  
Breast Cancer Management ◽  
Positive Breast Cancer

BACKGROUND Management of cancer patients in the current era of COVID-19 pandemic poses a significant challenge on health care systems. OBJECTIVE We explored the views of oncologists for the management of breast cancer patients during COVID-19 pandemic. METHODS A web-based questionnaire using SurveyMonkey was submitted to licensed oncologists involved in breast cancer management in Saudi Arabia, Egypt and United Arab Emirates. The survey focused on characteristics of participants, infection risk among cancer patients and possible treatment modifications related to different types of breast cancer RESULTS The survey was completed by 82 participants. For early HR positive, HER2-negative breast cancer,74.4% supported using neoadjuvant hormonal therapy in selected patients, and 58.0% preferred giving 6 over 8 cycles of adjuvant chemotherapy when indicated. Only 42.7% preferred CDK4/6 inhibitor with hormonal therapy as first line in all patients with metastatic HR-positive disease. 67.1% of participants supported using adjuvant trastuzumab for 6 instead of 12 months in selected patients with HER2-positive breast cancer. For metastatic HER2-positive, HR-positive breast cancer, 80.5% of participants supported the use of hormonal therapy with dual anti-HER2 blockade in selected patients. The preferred choice of 1st line treatment in metastatic triple negative patients with BRCA mutation and PDL1<1%, was PARP inhibitor according to 42.5% of the participants, and atezolizumab with nabpaclitaxel if the PDL1>1% according to 70.4% of the participants. CONCLUSIONS Several modifications in breast cancer management is supported by the survey participants. These modifications need to be discussed on local basis taking into account the local infrastructure and available resources. CLINICALTRIAL none

scholarly journals Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial

2020 ◽  
Vol 38 (27) ◽  
pp. 3138-3149 ◽  
Author(s):  
Cristina Saura ◽  
Mafalda Oliveira ◽  
Yin-Hsun Feng ◽  
Ming-Shen Dai ◽  
Shang-Wen Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Her2 Positive ◽  
End Points ◽  
Cns Disease

PURPOSE NALA (ClinicalTrials.gov identifier: NCT01808573 ) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens. METHODS Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL). RESULTS A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P = .043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P = .0004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups. CONCLUSION N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.

Venous thromboembolism in breast cancer patients receiving cyclin-dependent kinase inhibitors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18184-e18184
Author(s):  
Lorenzo Gervaso ◽  
Alberto J. Montero ◽  
Xuefei Jia ◽  
Alok A. Khorana
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Kinase Inhibitors ◽  
Cleveland Clinic ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Cyclin Dependent Kinase ◽  
Breast Cancer Patients

e18184 Background: Venous thromboembolism (VTE) complicates several anti-cancer regimens including chemotherapy and anti-angiogenic agents. Cyclin-dependent kinase 4/6 inhibitors (CDKIs) are a new approach for hormone receptor positive (HR+) metastatic breast cancer (mBC). Reported VTE rates in randomized trials range from 0.6% for ribociclib (MONALEESA-2) to 2% for palbociclib (PALOMA-3) and 5% for abemaciclib (MONARCH-3) but these may underestimate actual rates compared to patients in clinical practice who are generally older and have greater comorbidities. Little is known about real world incidence or prevalence of VTE with CDKIs in mBC. The aim of this study was to evaluate rates of VTE in clinical practice and association with outcomes in mBC patients on CDKIs. Methods: We conducted a retrospective cohort study at Cleveland Clinic Taussig Cancer Institute, approved by the institutional review board. We identified consecutive mBC patients who received any of three FDA-approved CDKIs (palbociclib, ribociclib, abemaciclib) from 1/2015 through 12/2017. VTE including deep venous thrombosis (DVT) and pulmonary embolism (PE) were identified by electronic medical record review. Overall survival (OS), progression free survival (PFS) and time to VTE were estimated by the Kaplan-Meier method and evaluated for association with VTE using Cox proportional hazard regression. Results: The study population included 424 patients, with a median age at diagnosis of 54.76 yrs, (range 27 -85). Palbociclib was the most commonly used CDKI (n = 390, 91.8%); 27 patients (6.3%) received more than one drug. VTE during CDKI therapy occurred in 9% of patients (n = 38), including DVT in 52.6% (n = 20), PE in 18.5% (n = 7) and visceral vein thrombosis (VVT) in 15.8% (n = 6). Median time to VTE was 314 days, and 6-months rate was 4.1%. VTE was associated with numerically worse PFS and OS, but this was not statistically significant (PFS [HR 1.25, 95% CI 0.73 – 2.14, p = 0.42], OS [HR 1.60, 95% CI 0.89 – 2.87, p = 0.12]). Conclusions: VTE affected nearly 10% of breast cancer patients receiving CDKIs, 2- to 5-fold greater than reported in registration trials. Further work is necessary to identify pathophysiology, risk factors and benefit of thromboprophylaxis.

Sign in / Sign up

Export Citation Format

Share Document