Clinical Outcomes of Breast Leptomeningeal Disease Treated with Intrathecal Trastuzumab, Intrathecal Chemotherapy, or Whole Brain Radiation Therapy

Figura, Nicholas; Mohammadi, Homan; Rizk, Victoria T.; Evernden, Brittany; Mokhtari, Sepideh; Yu, Hsiang‐Hsuan Michael; Robinson, Timothy J.; Etame, Arnold B.; Tran, Nam; Díaz, Roberto; Soliman, Hatem; Han, Heather; Sahebjam, Solmaz; Ahmed, Kamran A.

doi:10.1016/s0360-3016(19)30416-x

Cited by 3 publications

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“…In those reports, PFS6 was reported of 26%, and median OS, 3.3-5.4 mo). [17][18][19][20][21][22][23][24][25][27][28][29][30][31][32] The number of long-term survivors in our group (OS12, 35.5%, OS24, 19.4%) also compares favorably with that previously reported(OS12, 8%-31%). 19,22,23,31 Note is made that preliminary data for intra-CSF trastuzumab in treatment of Her2 + LM patients has been promising (median PFS, 5.7-7.5 months; PFS6 = 41%; median OS, 13.5-10.6 months).…”

Section: Discussionsupporting

confidence: 76%

“…10 When topotecan is administered by intraventricular route in humans at the MTD of 0.4 mg, the AUC is 21 micromolar-hour, T 1/2α is 26 ± 9 minutes, and T 1/2β is 174 ± 72 minutes. 5,10,14 Following intra-CSF treatment of patients with LM and breast cancer, survival has typically ranged from 2.9-5.4 months, 4,[15][16][17][18][19][20][21][22][23][24] and up to 13.6 months in HER2+ patients treated with intra-CSF trastuzumab. 25 Prior studies with intra-CSF TOPO treatment have reported clearing of malignant CSF cells in 38% of children with refractory leptomeningeal leukemia 6 and 82% (9/11) of patients with primary CNS tumors 8 ; however, the duration of CSF clearing in those studies was not reported.…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that local-field radiation therapy at baseline for bulky or symptomatic disease (74%), concomitant hormonal (50%) or systemic chemotherapy (46%) might have influenced outcome; however, it is noted that these concomitant therapies have been provided in conjunction with intra-CSF therapy in previously reported studies. 4,[17][18][19]21,22,[27][28][29][30][31][32] Given that 74% of our patients received local field RT at baseline, we acknowledge that the results likely reflect that achievable with the combination of RT (when clinically warranted) followed by intraventricular topotecan, and not just due to topotecan alone. In our study, the observed neurologic PFS6 of 39% and median OS 6.9 months are notable, particularly when compared with prior reports involving breast cancer patients with LM treated with a variety of systemic or intra-CSF agents, given alone or in combination with systemic therapy and/or radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

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Intra‐CSF topotecan in treatment of breast cancer patients with leptomeningeal metastases

et al. 2020

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Background There are few treatment options for patients with leptomeningeal metastases (LM). Methods We report a case series of patients with breast cancer and LM treated with intra‐CSF topotecan (TOPO). Outcome was assessed by clinical exam and MRI at baseline, at end of induction (4‐5 weeks), then every 3 months; CSF cytology was determined at baseline and with each treatment. Results Thirty‐one women [median age, 58 (37‐81); median KPS 60 (40‐100)] received treatment. At baseline, 68% had positive CSF cytology, and 90%, leptomeningeal enhancement on MRI. 84% of patients also received focal RT (not during TOPO) and 77% received concomitant systemic hormonal or chemotherapy. Median number of TOPO treatments was 14.5 (range, 3‐71); median duration of treatment, 11 weeks (1‐176); and median OS, 6.9 months (range, 0.9‐48.8). Patients remaining progression‐free during 4‐6 weeks of induction (81%) had a median OS of 11.5 months (range, 1.8‐48.8). Overall neurologic PFS at 6, 12, and 24 months was 39%, 26%, and 6%, respectively. Clearing of CSF malignant cells for >3 consecutive samples occurred in 10/21 (48%) patients with positive CSF cytology at baseline, remaining clear for a median duration of 15.9 months (range, 1.4‐34.5). Grade 3 adverse events included headache or vomiting (3pts), T2 hyperintensity surrounding the ventricular catheter (2 pts), and meningitis (2 pts). Conclusions Intra‐CSF TOPO, with focal RT as needed for symptomatic areas of enhancement produced durable clearing of CSF malignant cells in 48% of patients positive at baseline, with promising median PFS and OS.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Intra‐CSF topotecan in treatment of breast cancer patients with leptomeningeal metastases

et al. 2020

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“…In this trial, although approximately 50% of these patients had luminal ABC, only a small minority received ET. However, evidence shows that if BC-LMD is treated according to its molecular characteristics, better results are achieved [3,40,55,65,68].…”

Section: Discussionmentioning

confidence: 99%

Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review

et al. 2020

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Leptomeningeal disease (LMD) represents a devastating complication of advanced breast cancer (ABC), with survival of <5 months with multimodal treatment. The role of endocrine therapy (ET), due to its favorable toxicity profile and first-line indication in luminal ABC, appears promising in the setting of LMD, where symptom stabilization and quality-of-life preservation are the main goals; however, evidenced-based data are lacking. We conducted a thorough review of published evidence, aiming to investigate the role of ET in LMD treatment in luminal ABC. Twenty-one of 342 articles, evaluating 1302 patients, met inclusion criteria. ET use was rarely reported. New targeted agents show CNS activity. Research is lacking on the role of ET and targeted agents in BC-LMD treatment.

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“…A single institution retrospective review of breast cancer LM treatments found a 6-month CNS-PFS of 44% for intrathecal trastuzumab, 18% for intrathecal chemotherapy, and 26% for WBRT. OS was also longer among the intrathecal trastuzumab cohort (54% alive at 12 months compared to 10% for intrathecal chemotherapy and 19% for WBRT, respectively), although confounded by the enrichment of systemic disease and triple-negative breast cancer among the intrathecal chemotherapy and WBRT cohorts [98]. A subsequent meta-analysis of intrathecal trastuzumab across 24 articles calculated a CNS-PFS of 5.2 months (N = 39) and median OS of 13.2 months (N = 54) [99].…”

Section: Her2-positive Breast Cancermentioning

confidence: 96%

Leptomeningeal Metastases: New Opportunities in the Modern Era

Wilcox

Boire

2022

Neurotherapeutics

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Leptomeningeal metastases arise from cancer cell entry into the subarachnoid space, inflicting significant neurologic morbidity and mortality across a wide range of malignancies. The modern era of cancer therapeutics has seen an explosion of molecular-targeting agents and immune-mediated strategies for patients with breast, lung, and melanoma malignancies, with meaningful extracranial disease control and improvement in patient survival. However, the clinical efficacy of these agents in those with leptomeningeal metastases remains understudied, due to the relative rarity of this patient population, the investigational challenges associated with studying this dynamic disease state, and brisk disease pace. Nevertheless, retrospective studies, post hoc analyses, and small prospective trials in the last two decades provide a glimmer of hope for patients with leptomeningeal metastases, suggesting that several cancer-directed strategies are not only active in the intrathecal space but also improve survival against historical odds. The continued development of clinical trials devoted to patients with leptomeningeal metastases is critical to establish robust efficacy outcomes in this patient population, define drug pharmacokinetics in the intrathecal space, and uncover new avenues for treatment in the face of leptomeningeal therapeutic resistance.

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Clinical Outcomes of Breast Leptomeningeal Disease Treated with Intrathecal Trastuzumab, Intrathecal Chemotherapy, or Whole Brain Radiation Therapy

Cited by 3 publications

References 0 publications

Intra‐CSF topotecan in treatment of breast cancer patients with leptomeningeal metastases

Intra‐CSF topotecan in treatment of breast cancer patients with leptomeningeal metastases

Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review

Leptomeningeal Metastases: New Opportunities in the Modern Era

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