scholarly journals TRLS-09. RTOG1119: PHASE II RANDOMIZED STUDY OF WHOLE BRAIN RADIOTHERAPY / STEREOTACTIC RADIOSURGERY IN COMBINATION WITH CONCURRENT LAPATINIB IN PATIENTS WITH BRAIN METASTASIS FROM HER2-POSITIVE BREAST CANCER

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i10-i10
Author(s):  
In Ah Kim ◽  
Kathryn Winter ◽  
David Peereboom ◽  
Paul Sperduto ◽  
Jennifer De Los Santos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Disease Control ◽  
Stereotactic Radiosurgery ◽  
Surgical Resection ◽  
Response Rate ◽  
Her2 Positive ◽  
Positive Breast Cancer

Abstract The addition of trastuzumab to cytotoxic chemotherapy has improved outcomes for patients with HER2 positive breast cancer. Increased survival coupled with limited blood-brain barrier (BBB) penetration of trastuzumab may contribute to the increased incidence of brain metastasis in these patients. Half of these patients die of intracranial disease progression rather than extracranial disease. Therefore, strategies to improve survival must include increased CNS disease control in these patients. Lapatinib crosses the BBB and demonstrates modest activity against intracranial metastases. Based upon preclinical data and results of a phase I study, we hypothesized that lapatinib plus WBRT /SRS can improve the intracranial disease control compared to WBRT / SRS alone. A randomized phase II trial of WBRT (37.5 Gy/3 weeks) or SRS plus or minus concurrent lapatinib (daily 1000 mg for 6 weeks) was initiated. CNS penetrating HER2 targeted therapy is permitted throughout the study, but patients not on trastuzumab, pertuzumab or any other breast cancer therapy at study entry are not permitted to begin this therapy while on protocol treatment, but may begin it 24 hours after completion of protocol treatment. Eligibility includes HER2+ breast cancer with at least one measurable, unirradiated parenchymal brain metastasis. The two populations targeted for accrual include patients with 1) newly diagnosed, multiple brain metastases or 2) progressive brain metastases after stereotactic radiosurgery (SRS) or surgical resection of 1–3 metastases. Prior lapatinib is allowed. Patients are stratified by breast-specific graded prognostic assessment; use of non-CNS penetrating HER2 targeted therapy; and prior SRS or surgical resection. The primary endpoint is complete response rate in the brain 12 weeks after WBRT. Secondary endpoints include objective response rate, lesion-specific response rate, CNS progression-free survival, and overall survival. 140 of 143 target accrual have enrolled (4/22/2019).

RADT-03. OUTCOMES OF PATIENTS WITH HER2-POSITIVE BREAST CANCER METASTATIC TO BRAIN TREATED WITH HER2-TARGETED SYSTEMIC THERAPY AND STEREOTACTIC RADIOSURGERY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi41-vi41
Author(s):  
John Shumway ◽  
Marina Torras ◽  
Katherine Reeder-Hayes ◽  
Trevor Jolly ◽  
Elizabeth Dees ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Stereotactic Radiosurgery ◽  
Systemic Therapy ◽  
Survival Outcomes ◽  
Maximal Dimension ◽  
Her2 Positive ◽  
Intracranial Metastasis ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Abstract OBJECTIVE For patients with HER2-positive breast cancer metastatic to brain, HER2-directed systemic therapies are increasingly used with stereotactic radiosurgery (SRS). These include monoclonal antibodies such as trastuzumab (H) and pertuzumab (P), antibody-drug conjugates such as ado-trastuzumab emtansine (T-DM1), and tyrosine kinase inhibitors such as lapatinib. Limited data exist regarding appropriate timing with SRS and outcomes of this treatment regimen. METHODS A single-institution retrospective review collected clinical data on patients with breast cancer metastatic to brain who were treated with SRS from 2009-2020. Statistical analyses were performed using the Kaplan-Meier method and chi-square statistic. RESULTS Of 82 patients with breast cancer metastatic to brain treated with SRS, 33 (40%) were HER2-positive, 18 of whom were hormone receptor-positive. At brain metastasis diagnosis, 15 patients (45%) had >1 intracranial metastasis (range 2-7), and the median brain metastasis maximal dimension was 2.0 cm. Fifteen patients had uncontrolled extracranial disease. After brain metastasis diagnosis, 9 patients (27%) were treated with systemic therapy first (T-DM1+/-HP, lapatinib+HP, chemotherapy+/-HP) followed by SRS at a median of 18.6 months after starting systemic therapy. Seven patients (21%) were treated with SRS first, followed by systemic therapy in 6 of these patients (multi-agent regimens, 4 including T-DM1 or lapatinib). Seventeen (52%) received concurrent systemic therapy and SRS (T-DM1+/-chemotherapy, lapatinib, HP, hormone therapy, chemotherapy). Median follow-up time was 21.1 months. Median overall survival was 24.8 months and not statistically different between treatment groups. Four patients (12%) developed symptomatic radionecrosis; 3 were on T-DM1 concurrent with SRS. CONCLUSION In this small patient sample, we noted favorable survival outcomes for patients with HER2-positive breast cancer metastatic to brain when treated with HER2-targeted therapies together with SRS. The sequence of systemic therapy and SRS does not appear to impact survival outcomes. Concurrent treatment with T-DM1 and SRS may be associated with higher rates of radionecrosis.

scholarly journals HER2-targeted therapy prolongs survival in patients with HER2-positive breast cancer and intracranial metastatic disease: a systematic review and meta-analysis

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Anders W Erickson ◽  
Farinaz Ghodrati ◽  
Steven Habbous ◽  
Katarzyna J Jerzak ◽  
Arjun Sahgal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Metastatic Disease ◽  
Response Rate ◽  
Meta Analysis ◽  
Adverse Event Rate ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Intracranial Metastatic Disease ◽  
Positive Breast Cancer

Abstract Background Intracranial metastatic disease (IMD) is a serious and known complication of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The role of targeted therapy for patients with HER2-positive breast cancer and IMD remains unclear. In this study, we sought to evaluate the effect of HER2-targeted therapy on IMD from HER2-positive breast cancer. Methods We searched MEDLINE, EMBASE, CENTRAL, and gray literature sources for interventional and observational studies reporting survival, response, and safety outcomes for patients with IMD receiving HER2-targeted therapy. We pooled outcomes through meta-analysis and examined confounder effects through forest plot stratification and meta-regression. Evidence quality was evaluated using GRADE (PROSPERO CRD42020161209). Results A total of 97 studies (37 interventional and 60 observational) were included. HER2-targeted therapy was associated with prolonged overall survival (hazard ratio [HR] 0.47; 95% confidence interval [CI], 0.39–0.56) without significantly prolonged progression-free survival (HR 0.52; 95% CI, 0.27–1.02) versus non-targeted therapy; the intracranial objective response rate was 19% (95% CI, 12–27%), intracranial disease control rate 62% (95% CI, 55–69%), intracranial complete response rate 0% (95% CI, 0–0.01%), and grade 3+ adverse event rate 26% (95% CI, 11–45%). Risk of bias was high in 40% (39/97) of studies. Conclusion These findings support a potential role for systemic HER2-targeted therapy in the treatment of patients with IMD from HER2-positive metastatic breast cancer.

scholarly journals 34. TARGETED THERAPY FOR HER2-POSITIVE BREAST CANCER BRAIN METASTASES: A SYSTEMATIC REVIEW AND META-ANALYSIS

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
Anders Erickson ◽  
Farinaz Ghodrati ◽  
Sunit Das
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Meta Analyses ◽  
Positive Breast Cancer

Abstract INTRO One in three women with HER2-positive breast cancer will develop brain metastases, or intracranial metastatic disease (IMD). Historically, treatment of IMD has been confined to surgery and radiotherapy, with a limited role for chemotherapy. However, recent interest has burgeoned in a role for targeted therapy for treatment of IMD. The lack of high-level evidence, such as meta-analyses, regarding the role of targeted therapy in the management of IMD has prevented its inclusion in guidelines directing treatment. We performed a systematic review and meta-analysis to clarify the role of targeted therapy for IMD in women with HER2-positive breast cancer. METHODS Following PRISMA guidelines, a search of MEDLINE, CENTRAL, EMBASE, Google Scholar, and grey literature sources was conducted by two independent reviewers. Controlled trials and cohort studies that reported survival, safety, or response outcomes for patients receiving HER2-targeted therapy following IMD diagnosis were included. Meta-analyses using a random-effects model were conducted for OS and PFS. RESULTS 111 studies reporting on 8226 patients were included. Primary analysis of only RCTs found that HER2-targeted therapy was associated with improved OS (HR 0.63; 95% CI, 0.46–0.86; n = 392) but not PFS (HR 0.75; 95% CI, 0.30–1.85; n = 392) following IMD diagnosis. Secondary analysis combining RCTs and comparative observational studies found that HER2-targeted therapy was associated with improved OS (HR 0.42; 95% CI, 0.35–0.51; n = 2756) but not PFS (HR 0.58; 95% CI, 0.27–1.21; n = 460) following IMD diagnosis. Full analysis will be conducted for all 111 studies for pre-specified outcomes including intracranial PFS. CONCLUSION These findings support a potential role for HER2-targeted therapy in the management of IMD from HER2-positive breast cancer. Final analysis will synthesize current evidence for outcomes of intracranial response, survival, and safety.

scholarly journals Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3540
Author(s):  
Hamid Maadi ◽  
Mohammad Hasan Soheilifar ◽  
Won-Shik Choi ◽  
Abdolvahab Moshtaghian ◽  
Zhixiang Wang
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Cancer Patients ◽  
Mechanism Of Action ◽  
Mechanisms Of Action ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Insight Into ◽  
Positive Breast Cancer

Trastuzumab as a first HER2-targeted therapy for the treatment of HER2-positive breast cancer patients was introduced in 1998. Although trastuzumab has opened a new avenue to treat patients with HER2-positive breast cancer and other types of cancer, some patients are not responsive or become resistant to this treatment. So far, several mechanisms have been suggested for the mode of action of trastuzumab; however, the findings regarding these mechanisms are controversial. In this review, we aimed to provide a detailed insight into the various mechanisms of action of trastuzumab.

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