Targeted Therapy in Brain Metastases: Ready for Primetime?

2016 ◽  
pp. e123-e130 ◽  
Author(s):  
Vyshak A. Venur ◽  
Manmeet S. Ahluwalia
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Targeted Therapies ◽  
Future Directions ◽  
Anaplastic Lymphoma ◽  
Cancer Breast ◽  
Current State ◽  
Her2 Mutation

Brain metastasis is a serious complication of cancer that causes significant morbidity for patients. Over the last decade, numerous new driver somatic mutations have been recognized and targeted therapies are changing the landscape of treatment in lung cancer, breast cancer, and melanoma, which are also the three most common cancers that result in brain metastases. The common actionable mutations include the EGFR mutation and anaplastic lymphoma kinase (ALK) translocations in non–small cell lung cancer, the HER2 mutation in breast cancer, and the BRAF mutation in melanoma. However, most of the early trials with targeted agents excluded patients with brain metastases. With a better understanding of the biology, several recent trials of targeted therapy that focus on brain metastases have been reported and others are ongoing. Novel agents with better penetration across the blood–brain barrier are currently being investigated for patients with brain metastases. In this review, we discuss the current state of use and future directions of targeted therapies in brain metastases.

Temozolomide therapy for patients with non-small cell lung cancer, breast cancer, or melanoma brain metastases.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e12539-e12539
Author(s):  
D. R. Naskhletashvili ◽  
V. A. Gorbunova ◽  
M. B. Bychkov ◽  
G. E. Chmutin ◽  
V. B. Karahan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cancer Breast ◽  
Melanoma Brain Metastases

scholarly journals THER-01. Targeted therapy and intracranial metastatic disease: a population-based retrospective cohort study

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii12-iii12
Author(s):  
Anders Erickson ◽  
Steven Habbous ◽  
Frances Wright ◽  
Aisha Lofters ◽  
Katarzyna Jerzak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Retrospective Cohort ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Intracranial Metastatic Disease ◽  
Positive Breast Cancer

Abstract Background Targeted therapies have been hypothesized to prolong survival in the management of patients with intracranial metastatic disease (IMD), but, paradoxically, to increase IMD incidence by improving systemic disease control and prolonging survival from the primary tumor. The real-world benefits of targeted therapy in management of patients with IMD are unclear, as clinical trials have excluded patients with IMD and lacked endpoints reporting intracranial outcomes. Methods This retrospective cohort study included all patients in Ontario, Canada, diagnosed with IMD from 2005 to 2018 with primary diagnoses of breast cancer, lung or bronchus cancer, or melanoma, and control patients matched by primary disease without IMD. Kaplan-Meier and multivariable Cox regression analyses were performed to compare overall survival (OS) between patient sub-cohorts divided by primary disease and stratified by targeted therapy receipt or IMD status. Results Post-IMD targeted therapy was associated with prolonged OS in patients with HER2-positive breast cancer (HR 0.41; 95% CI, 0.33–0.5), EGFR-positive lung cancer (HR 0.28; 95% CI, 0.23–0.34), and BRAF-positive melanoma (HR 0.2; 95% CI, 0.14–0.29), compared to those who did not receive post-IMD targeted therapy. Presence of IMD was associated with shorter OS in patients with metastatic HER2-positive breast cancer (HR 1.8; 95% CI, 1.56–2.08) and metastatic EGFR-positive lung cancer (HR 1.22; 95% CI, 1.08–1.39) but not metastatic BRAF-positive melanoma (HR 1.11; 95% CI, 0.77–1.61), compared to those without IMD. Conclusions Our findings show that real-world use of targeted therapies was associated with prolonged OS in patients with IMD in the setting of HER2-positive breast cancer, EGFR-positive lung cancer, and BRAF-positive melanoma. Inclusion of patients with IMD in clinical trials and use of endpoints that interrogate IMD will be critical to determine the role of targeted therapies in the management of patients with IMD.

scholarly journals Systemic therapy of brain metastases: non–small cell lung cancer, breast cancer, and melanoma

2016 ◽  
Vol 19 (1) ◽  
pp. i1-i24 ◽  
Author(s):  
Marc C. Chamberlain ◽  
Christina S. Baik ◽  
Vijayakrishna K. Gadi ◽  
Shailender Bhatia ◽  
Laura Q.M. Chow
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Systemic Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cancer Breast

scholarly journals Tumor microenvironment differences between primary tumor and brain metastases

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Bernardo Cacho-Díaz ◽  
Donovan R. García-Botello ◽  
Talia Wegman-Ostrosky ◽  
Gervith Reyes-Soto ◽  
Elizabeth Ortiz-Sánchez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Brain Metastases ◽  
Primary Tumor ◽  
Scientific Literature ◽  
Metastatic Cancer ◽  
Primary Site ◽  
Cancer Breast

AbstractThe present review aimed to discuss contemporary scientific literature involving differences between the tumor microenvironment (TME) in melanoma, lung cancer, and breast cancer in their primary site and TME in brain metastases (BM). TME plays a fundamental role in the behavior of cancer. In the process of carcinogenesis, cells such as fibroblasts, macrophages, endothelial cells, natural killer cells, and other cells can perpetuate and progress carcinogenesis via the secretion of molecules. Oxygen concentration, growth factors, and receptors in TME initiate angiogenesis and are examples of the importance of microenvironmental conditions in the performance of neoplastic cells. The most frequent malignant brain tumors are metastatic in origin and primarily originate from lung cancer, breast cancer, and melanoma. Metastatic cancer cells have to adhere to and penetrate the blood–brain barrier (BBB). After traversing BBB, these cells have to survive by producing various cytokines, chemokines, and mediators to modify their new TME. The microenvironment of these metastases is currently being studied owing to the discovery of new therapeutic targets. In these three types of tumors, treatment is more effective in the primary tumor than in BM due to several factors, including BBB. Understanding the differences in the characteristics of the microenvironment surrounding the primary tumor and their respective metastasis might help improve strategies to comprehend cancer.

THE PREVALENCE OF HEPATITIS B REACTIVATION (HBV) IN CANCER PATIENTS TREATING WITH CHEMOTHERAPY

2016 ◽  
pp. 74-80
Author(s):  
Phuong Phung ◽  
Thi Thuy Nguyen
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Hepatitis B ◽  
Cancer Patients ◽  
Positive Control ◽  
High Dose ◽  
Hbv Reactivation ◽  
Endemic Region ◽  
Hepatitis B Reactivation ◽  
Cancer Breast

ackground and Objectives: Nowadays, the incidence of cancer is constantly increasing in the world as well as in Vietnam. The treatment of cancer is based on multimodality principle. Among those principal modalities, chemotherapy is widely used for different purposes such as neoadjuvant, andjuvant and palliation. However, chemotherapy can induce activation of latent infections, including hepatitis B. Vietnam is in the endemic region of hepatitis B so the reactivation of hepatitis B on cancer patients with chemotherapy has emerged a concerned problem. However, few interests were gained on this problem in the aspect of clinical setting or researching. Aims: to determine the prevalence of hepatitis B reactivation (HBV) in cancer patients treating with chemotherapy and to detect some risks factors of this situation. Subjects and methods: descriptive prospective. The study included 33 cancer patients with inactive HBV infection who are treating with chemotherapy. We define HBV reactivation by ALT > 3 ULN and HBV DNA copies > 10 positive control limit. Results: We found 6 patients with reactivated HBV, accounting for 18.18 %. Among reactivated HBV patients, age less than 60 accounts 83,33%. Rate of reactivated HBV in males was 25,00% while this rate in females was 14,28%. Rate of reactivated HBV in lymphoma, lung cancer and breast cancer was 33,33%, 25% và 22,22% respectively. Clinial manifestation of reactivated HBV includes jaundice (33,33%), fulminant hepatic failure (6%) and death (5%). The reactivated rate was higher in patients got high dose of corticoid (28,57%) vs low dose (15,38%). This rate was 29,41% in patients treated with anthracyclines which was higher than in group without anthracyclines. The reactivated rate of HBV was dramatically higher in patients treated with rituximab (75%). Conclusion: the reactivation of hepatitis B on cancer patients with chemotherapy is common. We found 6 patients with reactivated HBV of 33 subjects of the study which accounts 18.18 %. We recognized that reactivated HBV rate was higher subgroups of age < 60 years old, males, patients with lymphoma, lung cancer, breast cancer. Reactivated HBV may be more prevalent in patients with high-dose corticotherapy, anthracyclines and Rituximab. Key words: HBV reactivation, chemotherapy, cancer, hepatitis B

scholarly journals Does lung cancer mutation status and targeted therapy predict for outcomes and local control in the setting of brain metastases treated with radiation?

2015 ◽  
Vol 17 (7) ◽  
pp. 1022-1028 ◽  
Author(s):  
Tony J. C. Wang ◽  
Shumaila Saad ◽  
Yasir H. Qureshi ◽  
Ashish Jani ◽  
Tavish Nanda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Local Control ◽  
Mutation Status ◽  
Cancer Mutation

Brigatinib is a cost-effective treatment in first-line anaplastic lymphoma kinase mutation-positive (ALK + ) advanced non-small cell lung cancer (NSCLC) with brain metastases

2022 ◽  
pp. 107815522110734
Author(s):  
Jacopo Giuliani
Keyword(s):  
Lung Cancer ◽  
Cost Effectiveness ◽  
Brain Metastases ◽  
Cost Effective ◽  
Small Cell ◽  
Control Group ◽  
Small Cell Lung ◽  
First Line ◽  
Anaplastic Lymphoma ◽  
Kinase Mutation

Introduction The aim of this paper was to assess the cost-effectiveness of alectinib and brigatinib in first-line for anaplastic lymphoma kinase mutation-positive (ALK+) advanced non-small cell lung cancer (NSCLC). Pivotal phase III RCTs were considered. Four hundred and eighty-two patients were included. Both trials, which compared alectinib and brigatinib versus (vs.) crizotinib (control group), respectively, showed a gain in pharmacological costs, compared to the control group, of 194.80 € for alectinib and 648.48 € for brigatinib for an entire treatment of a single patient. Brigatinib was the less expensive, with a cost of 269.78 € for each month of PFS for both intention-to-treat (ITT) population that patients with baseline brain metastases (BBM). In conclusion, combining pharmacological costs of drugs with the measure of efficacy represented by PFS, both alectinib and brigatinib are cost-effective treatments in first-line for ALK+ NSCLC. In the BBM population brigatinib seems to be the most cost-effectiveness.

scholarly journals Synthesis of Novel 1,2,3-Triazole-Dihydropyrimidinone Hybrids Using Multicomponent 1,3-Dipolar Cycloaddition (Click)–Biginelli Reactions: Anticancer Activity

Synlett ◽  
2020 ◽  
Vol 31 (06) ◽  
pp. 615-621
Author(s):  
Elisabete P. Carreiro ◽  
Ana M. Sena ◽  
Adrián Puerta ◽  
José M. Padrón ◽  
Anthony J. Burke
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Heterocyclic Ring ◽  
Small Cell ◽  
Dipolar Cycloaddition ◽  
Cancer Cervix ◽  
Small Cell Lung ◽  
Methyl Group ◽  
Cancer Breast ◽  
Biginelli Reactions

In this work, 21 novel (1,4-disubstituted 1,2,3-triazole)-dihydropyrimidinone (1,2,3-trzl-DHPM) type hybrids were synthesized and characterized. These were divided into two types: hybrids A (5 in total) containing the dihydropyrimidinone heterocyclic ring decorated with a 1,4-disubstituted 1,2,3-triazole in the C-5 position [these compounds were accessed by a multicomponent copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) (or click)–Biginelli reactions with satisfactory yields (39–57%)] and hybrids B (16 in total) containing two 1,2,3-triazole units in the C-5 and C-6 methyl position of the DHPM. Hybrids B were synthesized via functionalization of the C-6 methyl group of hybrids A, a multistep sequence of reactions was used that included bromination, azidation, and a CuAAC. Hybrids B were obtained in very good to excellent yields (up to 99%). Some hybrids A and B were evaluated for their antiproliferative activity against different cancer cell lines that included A549 and SW1573 (non-small-cell lung), HBL-100 and T-47D (breast), HeLa (cervix) and WiDr (colon). Three of these hybrids were potent cell proliferation inhibitors of non-small-cell lung cancer, cervix cancer, breast cancer, and colon cancer.

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