Effect of type and timing of systemic therapy on risk of radiation necrosis in patients with HER2+ breast cancer brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14002-e14002
Author(s):  
Christine Park ◽  
Evan Buckley ◽  
Amanda E.D. Van Swearingen ◽  
Will Giles ◽  
James Emmett Herndon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Radiation Necrosis ◽  
Treatment Modalities ◽  
Conformity Index ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis ◽  
The Impact ◽  
Systemic Therapies

e14002 Background: It is estimated that 30% of patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer will develop brain metastases. Current standard of care options for HER2+ breast cancer brain metastasis (BCBrM) includes radiation therapy (stereotactic radiosurgery [SRS] or whole brain radiation), brain permeable systemic therapies, and in select cases, neurosurgical resection. A multimodal approach combining these different treatment modalities has improved the overall survival and functional outcomes of patients with BCBrM. Some HER2-directed systemic therapies, however, may increase the risk of radiation necrosis (RN), a longer-term consequence of SRS. This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ BCBrM. Methods: This was a single-institution, retrospective study including patients ≥18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 at Duke University with at least 12-month post-SRS follow-up. Presence of RN was determined at one-year post-SRS. Demographics, radiotherapy parameters (total dose, fractions, clinical target volume [CTV], gross tumor volume [GTV], conformity index [CI], volume receiving 12 gray [V12Gy]), and timing (during [within 4 weeks of SRS] vs. not during SRS) and type of systemic therapy (HER2-directed therapy, mitosis inhibitors, DNA synthesis inhibitors, others) were evaluated. Results: Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not. Age at time of SRS did not differ between those who developed RN and those who did not (mean 53.3 vs 50.4 years, respectively). There was a higher percentage of African Americans in the RN group (28.6% vs 11.1%, p = 0.3). There were no significant differences between the measured radiotherapy parameters—including dose, fraction, CTV, GTV, CI, V12Gy—between the two groups (all p > 0.05). Receipt of any type of systemic therapy during SRS did not differ between patients who did or did not develop RN (60.7% vs 55.6%, p = 0.97). However, patients who developed RN more commonly received more than one line of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p = 0.08). In fact, a significantly higher proportion of those who developed RN received more than one line of HER2-directed therapy during SRS compared to those did not develop RN (35.7% vs 5.6%, p<0.05). Conclusions: Patients with HER2 BCBrM who receive multiple lines of HER2-directed therapy during SRS for BCBrM may be at higher risk of RN. This data supports a practice of holding HER2-directed therapy during SRS if medically acceptable. Further investigation of next generation HER2-directed therapies in a larger cohort of patients should be investigated to help guide best practice to minimize RN.

scholarly journals RADI-13. Systemic Therapy Type and Timing Effects on Radiation Necrosis Risk in HER2+ Breast Cancer Brain Metastases Patients Treated with Stereotactic Radiosurgery

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii20-iii20
Author(s):  
Christine Park ◽  
Evan Buckley ◽  
Amanda Van Swearingen ◽  
Will Giles ◽  
James Herndon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stereotactic Radiosurgery ◽  
Systemic Therapy ◽  
Radiation Necrosis ◽  
Standard Of Care ◽  
Current Standard ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis ◽  
The Impact ◽  
Systemic Therapies

Abstract Background Current standard of care options for HER2+ breast cancer brain metastasis (BCBrM) include radiation therapy, brain permeable systemic therapies, and in select cases, neurosurgical resection. There is a concern that HER2-directed systemic therapies when administered concurrently with stereotactic radiosurgery (SRS) may increase the risk of radiation necrosis (RN). This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ BCBrM. Methods This was a single-institution, retrospective study including patients ≥18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 with at least 12-month post-SRS follow-up. Presence of RN was determined at one-year post-SRS. Demographics, radiotherapy parameters, and timing (“during” defined as four weeks before/after SRS) and type of systemic therapy were evaluated. Results Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not. Age (mean 53.3 vs 50.4 years, respectively), radiotherapy parameters (dose, fraction, CTV, GTV, CI, V12Gy, all p&gt;0.05), and receipt of any type of systemic therapy during SRS (60.7% vs 55.6%, p = 0.97) did not differ between patients who did or did not develop RN. However, patients who developed RN more commonly received more than one line of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p = 0.08). In fact, a significantly higher proportion of those who developed RN received more than one line of HER2-directed therapy during a given SRS treatment compared to those did not develop RN (35.7% vs 5.6%, p&lt;0.05). Conclusions Patients with HER2+ BCBrM who receive multiple lines of HER2-directed therapy during SRS for BCBrM may be at higher risk of RN. Collectively, this data supports a practice of holding HER2-directed therapy during treatment with SRS if medically acceptable.

scholarly journals Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood–tumor barrier disruption

2018 ◽  
Vol 115 (37) ◽  
pp. E8717-E8726 ◽  
Author(s):  
Costas D. Arvanitis ◽  
Vasileios Askoxylakis ◽  
Yutong Guo ◽  
Meenal Datta ◽  
Jonas Kloepper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Experimental Data ◽  
Drug Delivery ◽  
Brain Metastases ◽  
Focused Ultrasound ◽  
Xenograft Model ◽  
Convective Transport ◽  
Pbpk Modeling ◽  
Breast Cancer Brain Metastasis ◽  
The Impact

Blood–brain/blood–tumor barriers (BBB and BTB) and interstitial transport may constitute major obstacles to the transport of therapeutics in brain tumors. In this study, we examined the impact of focused ultrasound (FUS) in combination with microbubbles on the transport of two relevant chemotherapy-based anticancer agents in breast cancer brain metastases at cellular resolution: doxorubicin, a nontargeted chemotherapeutic, and ado-trastuzumab emtansine (T-DM1), an antibody–drug conjugate. Using an orthotopic xenograft model of HER2-positive breast cancer brain metastasis and quantitative microscopy, we demonstrate significant increases in the extravasation of both agents (sevenfold and twofold for doxorubicin and T-DM1, respectively), and we provide evidence of increased drug penetration (>100 vs. <20 µm and 42 ± 7 vs. 12 ± 4 µm for doxorubicin and T-DM1, respectively) after the application of FUS compared with control (non-FUS). Integration of experimental data with physiologically based pharmacokinetic (PBPK) modeling of drug transport reveals that FUS in combination with microbubbles alleviates vascular barriers and enhances interstitial convective transport via an increase in hydraulic conductivity. Experimental data demonstrate that FUS in combination with microbubbles enhances significantly the endothelial cell uptake of the small chemotherapeutic agent. Quantification with PBPK modeling reveals an increase in transmembrane transport by more than two orders of magnitude. PBPK modeling indicates a selective increase in transvascular transport of doxorubicin through small vessel wall pores with a narrow range of sizes (diameter, 10–50 nm). Our work provides a quantitative framework for the optimization of FUS–drug combinations to maximize intratumoral drug delivery and facilitate the development of strategies to treat brain metastases.

EGF105084, a phase II study of lapatinib for brain metastases in patients (pts) with HER2+ breast cancer following trastuzumab (H) based systemic therapy and cranial radiotherapy (RT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1012-1012 ◽  
Author(s):  
N. U. Lin ◽  
V. Dieras ◽  
D. Paul ◽  
D. Lossignol ◽  
C. Christodoulou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Phase Ii ◽  
Systemic Therapy ◽  
Preliminary Data ◽  
Brain Lesion ◽  
Stage Iv ◽  
Cranial Radiotherapy ◽  
Cns Disease ◽  
Her2 Breast Cancer

1012 Background: CNS disease is a major problem among pts treated with H for stage IV HER2+ breast cancer with a reported incidence of 28–43%. This study was designed to characterize further the activity reported with lapatinib in an initial phase II trial in women with HER2+ disease metastatic to brain (Lin et al ASCO ‘06). Methods: Eligible pts had HER2+ breast cancer, prior H therapy and cranial RT, ECOG PS 0–2, and radiographic evidence of progressive brain metastases with at least one measurable (LD = 10mm) brain lesion. Pts received lapatinib 750 mg PO BID. Brain MRIs were obtained at 3.0 mm slices without gaps in the axial dimension. The primary endpoint was CNS response as defined by a = 50% volumetric (vol) reduction of CNS lesions in the absence of: new lesions, need for increased dose of steroids, progressive neurological signs/symptoms (NSS), or progressive extra-CNS disease. CNS disease progression was defined as either a = 40% vol increase from nadir, increase in steroid requirements, or progression of NSS. Results: The study exceeded its accrual goal of 220 pts in < 1 year; 238 pts were enrolled from Jan-Nov 06. Preliminary data from the initial 104 pts have undergone independent radiology review. 8 pts (7.7%) met vol criteria for partial response with a median absolute vol reduction of CNS disease of 3.6 cm3 (range 0.4 to 29.7 cm3). Exploratory analysis revealed that 17 of the initial 104 pts (16.3%) experienced a = 20% vol reduction of CNS disease with a median absolute vol reduction of 3.3cm3. The median time to vol progression in these 17 pts was 16 wks (range 12 -24 wks). Analysis of efficacy and tolerability based upon protocol defined criteria from all 238 pts will be presented. Conclusions: Preliminary data from this large multicenter trial provides evidence that lapatinib has activity based on vol reductions in pts with progressive HER2+ CNS disease following prior H-based systemic therapy and cranial RT. Definitive conclusions will be based on the entire database. Additional studies are warranted incorporating lapatinib in combination with other therapies and/or in a less refractory setting to optimize its use in HER2+ CNS disease. [Table: see text]

scholarly journals 143P The impact of de-escalation of adjuvant systemic therapy on the outcome of women with early ER+/HER2+ breast cancer

2021 ◽  
Vol 32 ◽  
pp. S423
Author(s):  
V. Jerič Horvat ◽  
D. Manevski ◽  
M. Pohar Perme ◽  
B. Gazić ◽  
P. Drev ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Therapy ◽  
Adjuvant Systemic Therapy ◽  
Her2 Breast Cancer ◽  
The Impact

EXTH-02. AAV MEDIATED BRAIN DELIVERY OF AN ADCC-ENHANCED ANTIBODY OBVIATES XENOGRAFT GROWTH IN MOUSE MODELS OF HER2+ BREAST CANCER BRAIN METASTASIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi163-vi163
Author(s):  
Dan Laks ◽  
Kenny Chen ◽  
Xiaoqin Ren ◽  
Ishan Shah ◽  
Usman Hameedi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Tumor Growth ◽  
Cancer Patients ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Aav Vector ◽  
Orthotopic Xenograft ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis

Abstract BACKGROUND HER2+ tumors constitute approximately 20% of breast cancer patients and are characterized by overexpression of the growth factor receptor HER2 (ERBB2), a cell proliferation driver. Effective anti-HER2 therapies confer prolonged patient survival necessitating the need for transformative treatments targeting brain metastases, a major cause of mortality in ~30-50% of HER2+ metastatic breast cancer patients. HER2-directed antibody immunotherapy, while efficacious for peripheral disease, has limited central nervous system exposure (CNS). To overcome these challenges, we transduced CNS cells with a novel AAV vector carrying an anti-HER2 antibody payload. METHODS We assessed the biochemical equivalence and functional effectiveness of AAV vector-encoded antibodies using in vitro assays. After selecting promising vector-encoded antibody candidates, a novel, blood-brain barrier penetrant AAV capsid was administered via i.v. dosing to an orthotopic xenograft mouse model of HER2+ brain metastases. Bioluminescent imaging provided a longitudinal measure of brain tumor burden. At study termination, we measured antibody biodistribution in cerebrospinal fluid (CSF), serum, and brain homogenates with AlphaLISA assays. RESULTS Using HER2+ breast cancer cell lines, we determined that an antibody-dependent cell cytotoxicity (ADCC) enhanced anti-HER2 antibody was most effective and demonstrated that AAV-vector encoded forms of the antibody performed comparably to recombinant reference antibodies. Following i.v. administration of a HER2 antibody encoding AAV vector, we measured &gt;1 ug/mL of the antibody in CSF. Importantly, AAV-mediated expression of the ADCC-enhanced HER2-directed antibody significantly abrogated tumor growth in orthotopic xenograft models. CONCLUSIONS Peripheral administration of an AAV vector was able to transduce brain tissue such that efficacious levels of HER2-directed antibodies were produced. This strategy was successful at preventing tumor growth in our physiologically relevant model of breast cancer brain metastases. Such a treatment modality should be further evaluated in patient derived PDX models to validate translational efficacy for human patients.

scholarly journals Outcomes of changing systemic therapy in patients with relapsed breast cancer and 1 to 3 brain metastases

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Omar Alhalabi ◽  
Zaid Soomro ◽  
Ryan Sun ◽  
Elshad Hasanov ◽  
Aya Albittar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Hazard Ratios ◽  
Significant Difference ◽  
Extracranial Disease ◽  
Initiation Of Therapy ◽  
The Impact

AbstractThe development of brain metastases (BMs) in breast cancer (BC) patients remains a challenging complication. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable extracranial disease. We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) following the diagnosis and management of oligometastatic (1–3) BMs in patients without extracranial metastases on the progression-free survival time (PFS), and overall survival (OS). Hazard ratios (HRs) were calculated using the Cox proportional hazard model. Among the 2645 patients with BC and BMs treated between 2002 and 2015, 74 were included for analysis. 40.5% of patients had HER2 + disease. Median time from diagnosis of BC to BMs was 17.6 months. 54%, 8%, and 38% of BMs were managed by radiation, craniotomy, or combination, respectively. Following the primary management of BMs, we observed that CST occurred in 26 (35.5%) patients, consisting of initiation of therapy in 13.5% and switching of ongoing adjuvant therapy in 22%. Median PFS was 6.6 months among patients who had CST compared to 7.1 months in those who did not (HR = 0.88 [0.52–1.47], p = 0.62). Median OS was 20.1 months among patients who had CST compared to 15.1 months in those who did not (HR = 0.68 [0.40–1.16], p = 0.16). Upon the successful local management of oligometastatic BMs in patients without extracranial disease, we did not find a significant difference in survival between patients who experienced a change in systemic therapy as compared to those who did not.

Systemic therapy for patients with breast cancer and one to three brain metastases (BM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1090-1090
Author(s):  
Zaid A Soomro ◽  
Omar Alhalabi ◽  
Ryan Sun ◽  
Aya Albittar ◽  
Limin Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Brain Metastases ◽  
Survival Time ◽  
Systemic Therapy ◽  
Local Therapy ◽  
Extracranial Disease ◽  
The Impact ◽  
Extracranial Metastases

1090 Background: Despite advances in systemic therapies and improved overall survival of metastatic breast cancer (MBC) patients, the development of brain metastases (BMs) remains a challenging complication that affects quality of life and increases morbidity and mortality. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable systemic disease. Methods: We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) after diagnosis of the initial 1-3 BMs on the patient’s progression-free survival time (PFS), defined as time to death, to a second BMs or to extracranial metastases. All MBC patients with 1 to 3 BMs only (without extracranial disease) treated at our institution between 2002 and 2017 were identified. For each patient, full information on follow-up and administered therapies were mandatory for inclusion. Hazard ratios (HR) were calculated using the Cox proportional hazard model. We also computed the restricted mean survival time (RMST) up to 5 years of follow-up. Results: Among the 2645 patient with BM treated at our institution, 80 were included for analysis. In regards to primary BMs management in patients, 46 of 80 (57%) were treated by radiation therapy, 6 of 80 (7.5%) underwent surgical resection, and 28 of 80 (35%) were managed by a combination of surgery and radiation therapy. All patients had staging imaging documenting lack of extracranial metastases at the time of local therapy of BMs. Following the primary management of BM, we observed that providers changed systemic therapy in 32 of 80 (40%), defined as the CST group. CST included both initiation of therapy in 16 of 80 (20%) and switching of adjuvant therapy in 16 of 80 (20%). Median PFS among CST was 7.7 months vs. 7.2 months among no CST (HR = 0.855, 95% confidence interval (CI) 0.53-1.38, p = 0.52). 5-year RMST for the CST group was 16.6 months vs. 12.8 months in no CST group. The difference of 3.8 months (95% CI 4.3-11.8) was not statistically significant. Conclusions: Patients with 1-3 BMs without extracranial disease had a median PFS close to 7.5 months after local therapy. Consistent with current standard of care of maintaining the same systemic therapy approach upon developing isolated BMs, our findings did not demonstrate a significant difference in PFS between patients who experienced a change in systemic therapy compared to those who did not.

scholarly journals Systemic treatment of HER2-positive breast cancer patients with brain metastases: current status and exploratory case study in a Portuguese cohort

2021 ◽  
Vol 18 (1) ◽  
pp. 1-14
Author(s):  
Paulo Luz ◽  
Elsa Campoa ◽  
Rita Gameiro ◽  
Marta Vaz ◽  
Isabel Fernandes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Systemic Treatment ◽  
Local Treatment ◽  
Current Status ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
The Impact

Over the last years, the incidence of brain metastases in HER2 breast cancer patients has increased. Surgery and radiotherapy are the current standard local therapies. Nevertheless, it is unclear which and when systemic treatment should be applied in addition to local treatment. This work aims to present an updated review of current systemic treatment options for patients with HER2+ metastatic breast cancer with brain metastases and to present a case study of clinical cases that occurred in a Portuguese population. The methodology of this work included a literature search in PubMed for the impact of HER2-targeting agents, such as pertuzumab, trastuzumab emtansine (T-DM1), lapatinib, neratinib, trastuzumab deruxtecan, and tucatinib in the treatment of patients with HER2+ breast cancer with brain metastases. Then, a cohort of Portuguese patients with HER2+ breast cancer (n=44) was analyzed. In this exploratory study, considering a follow-up of 23.9 months, three patients (6.8%) developed brain metastases despite having shown a complete pathological response. The role of systemic treatment for patients with HER2 breast cancer with brain metastases has rapidly evolved following recent successes in phase II and III clinical trials. The biggest challenge is how to integrate systemic and local treatment in the management of these patients.

Trends in diagnosis and treatment of early breast cancer (eBC) in the United States (US) during the COVID-19 era.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 227-227
Author(s):  
Benjamin Ackerman ◽  
Catherine Keane ◽  
Julia A. Beaver ◽  
Paul Gustav Kluetz ◽  
Donna Rivera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Screening ◽  
Systemic Therapy ◽  
Initial Treatment ◽  
The United States ◽  
Stage I ◽  
Treatment Modalities ◽  
Research Database ◽  
Cancer Outcomes ◽  
The Impact

227 Background: Recent studies have demonstrated a decline in cancer screening and diagnosis during the COVID-19 pandemic. This study explored trends in the diagnosis and management of eBC at a sample of cancer clinics across the US early on in the pandemic. Methods: Patients were selected from the Flatiron Health Research Database (FHRD), an electronic health record-derived de-identified database comprising approximately 280 US cancer clinics (̃800 sites of care). Eligible patients had an ICD code for breast cancer, at least two clinical encounters, and a confirmed eBC (Stage I-III) diagnosis from unstructured documents. Patients were selected into two cohorts based on diagnosis date: a) COVID-19 era cohort diagnosed between February 1, 2020 through June 30, 2020 and b) pre-COVID-19 era cohort diagnosed from February 1, 2019 through June 30, 2019. Descriptive statistics were used to assess diagnosis trends in each time frame. Initial treatment received following eBC diagnosis was categorized as surgery, radiation or systemic therapy and was compared between the two cohorts. Initial treatment modalities for each cohort were further stratified by clinical stage and biomarker subtype (HER2+, HR+/HER2-, triple negative [TN] or unknown). Results: A total of 278 and 253 patients were selected for the pre-COVID-19 era and COVID-19 era cohorts, with a median age at diagnosis of 65 and 64 years, respectively. A 35% decrease in the number of eBC diagnoses was observed in April/May 2020 compared to March 2020, yet this reduction in diagnoses was not observed during the equivalent months in the pre-COVID-19 era cohort. Compared to the pre-COVID-19 era, a greater proportion of patients diagnosed with eBC during the COVID-19 era initiated systemic therapy as their first treatment modality (16.5% vs 29.6%) including patients with HER2+ (27.5% vs. 60%), HR+/HER2- (13.5% vs. 24.9%) and TN (30.8% vs. 40.0%) disease. This trend was observed in patients with stage I (11.7% vs. 24.1%) or II (55.9% vs. 73.0%) but not in patients with stage III (81.2% vs. 77.3%) eBC. Notably, among patients with HR+/HER2- eBC who received systemic therapy as their first treatment, endocrine therapy was most commonly used in keeping with recent recommendations from professional societies due to COVID-related anticipated surgical delays. Conclusions: This study demonstrates that COVID-19 was associated with a decreased incidence of eBC which could be, at least in part, attributed to previously reported delays in routine screening and pandemic healthcare utilization. Further efforts are required to understand who was affected by these delays and the impact on cancer outcomes. Follow-up data are needed to understand if the observed trends in cancer screening and treatment persist and their impact on long-term cancer outcomes.

Stereotactic radiosurgery with concurrent lapatinib is associated with improved local control for HER2-positive breast cancer brain metastases

2020 ◽  
Vol 132 (2) ◽  
pp. 503-511 ◽  
Author(s):  
Shireen Parsai ◽  
Jacob A. Miller ◽  
Aditya Juloori ◽  
Samuel T. Chao ◽  
Rupesh Kotecha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Brain Metastases ◽  
Local Control ◽  
Radiation Necrosis ◽  
Growth Factor Receptor ◽  
Local Failure ◽  
Her2 Breast Cancer ◽  
Epidermal Growth ◽  
Breast Cancer Brain Metastases

OBJECTIVEWith increasing survival for patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer in the trastuzumab era, there is an increased risk of brain metastasis. Therefore, there is interest in optimizing intracranial disease control. Lapatinib is a small-molecule dual HER2/epidermal growth factor receptor inhibitor that has demonstrated intracranial activity against HER2+ breast cancer brain metastases. The objective of this study was to investigate the impact of lapatinib combined with stereotactic radiosurgery (SRS) on local control of brain metastases.METHODSPatients with HER2+ breast cancer brain metastases who underwent SRS from 1997–2015 were included. The primary outcome was the cumulative incidence of local failure following SRS. Secondary outcomes included the cumulative incidence of radiation necrosis and overall survival.RESULTSOne hundred twenty-six patients with HER2+ breast cancer who underwent SRS to 479 brain metastases (median 5 lesions per patient) were included. Among these, 75 patients had luminal B subtype (hormone receptor-positive, HER2+) and 51 patients had HER2-enriched histology (hormone receptor-negative, HER2+). Forty-seven patients received lapatinib during the course of their disease, of whom 24 received concurrent lapatinib with SRS. The median radiographic follow-up among all patients was 17.1 months. Concurrent lapatinib was associated with reduction in local failure at 12 months (5.7% vs 15.1%, p < 0.01). For lesions in the ≤ 75th percentile by volume, concurrent lapatinib significantly decreased local failure. However, for lesions in the > 75th percentile (> 1.10 cm3), concurrent lapatinib did not significantly improve local failure. Any use of lapatinib after development of brain metastasis improved median survival compared to SRS without lapatinib (27.3 vs 19.5 months, p = 0.03). The 12-month risk of radiation necrosis was consistently lower in the lapatinib cohort compared to the SRS-alone cohort (1.3% vs 6.3%, p < 0.01), despite extended survival.CONCLUSIONSFor patients with HER2+ breast cancer brain metastases, the use of lapatinib concurrently with SRS improved local control of brain metastases, without an increased rate of radiation necrosis. Concurrent lapatinib best augments the efficacy of SRS for lesions ≤ 1.10 cm3 in volume. In patients who underwent SRS for HER2+ breast cancer brain metastases, the use of lapatinib at any time point in the therapy course was associated with a survival benefit. The use of lapatinib combined with radiosurgery warrants further prospective evaluation.

Sign in / Sign up

Export Citation Format

Share Document