Phase I feasibility study for intrathecal administration of trastuzumab in patients with HER2 positive breast carcinomatous meningitis

Bonneau, Claire; Paintaud, Gilles; Trédan, Olivier; Dubot, Coraline; Desvignes, Céline; Dièras, Véronique; Taillibert, Sophie; Tresca, Patricia; Turbiez, Isabelle; Li, Jacques; Passot, Christophe; Mefti, F.; Mouret-Fourme, Emmanuelle; Rhun, Émilie Le; Gutierrez, Maya

doi:10.1016/j.ejca.2018.02.032

Cited by 79 publications

(47 citation statements)

References 21 publications

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“…To this effect, clinical trials are underway to administer immunotherapy intrathecally, with early reports suggesting that this approach is adequately safe to begin investigating efficacy compared to systemic treatments [91]. In addition, the intrathecal administration of trastuzumab has also been shown in multiple studies to be capable of eliciting responses in the treatment of HER2+ breast cancer LM [92][93][94].…”

Section: Systemic and Intrathecal Therapiesmentioning

confidence: 99%

The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers

Dankner

Lam

Degenhard

et al. 2021

Cancers

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Metastasis to the central nervous system occurs in approximately 20% of patients with advanced solid cancers such as lung cancer, breast cancer, and melanoma. While central nervous system metastases most commonly form in the brain parenchyma, metastatic cancer cells may also reside in the subarachnoid space surrounding the brain and spinal cord to form tumors called leptomeningeal metastases. Leptomeningeal metastasis involves cancer cells that reach the subarachnoid space and proliferate in the cerebrospinal fluid compartment within the leptomeninges, a sequela associated with a myriad of symptoms and poor prognosis. Cancer cells exposed to cerebrospinal fluid in the leptomeninges must contend with a unique microenvironment from those that establish within the brain or other organs. Leptomeningeal lesions provide a formidable clinical challenge due to their often-diffuse infiltration within the subarachnoid space. The molecular mechanisms that promote the establishment of leptomeningeal metastases have begun to be elucidated, demonstrating that it is a biological entity distinct from parenchymal brain metastases and is associated with specific molecular drivers. In this review, we outline the current state of knowledge pertaining to the diagnosis, treatment, and molecular underpinnings of leptomeningeal metastasis.

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Section: Systemic and Intrathecal Therapiesmentioning

confidence: 99%

The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers

Dankner

Lam

Degenhard

et al. 2021

Cancers

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“…Trastuzumab has been evaluated in a phase I study in patients with breast cancer with leptomeningeal metastases with Her2-positive tumours, with a good tolerance (NCT01373710). 9 Data of a second trial on safety of dose-escalated intrathecal trastuzumab are still pending (NCT01325207).…”

Section: Introductionmentioning

confidence: 99%

How we treat patients with leptomeningeal metastases

et al. 2019

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The goal of treatment of leptomeningeal metastasis is to improve survival and to maintain quality of life by delaying neurological deterioration. Tumour-specific therapeutic options include intrathecal pharmacotherapy, systemic pharmacotherapy and focal radiotherapy. Recently, improvement of leptomeningeal disease–related progression-free survival by adding intrathecal liposomal cytarabine to systemic treatment versus systemic treatment alone has been observed in a randomised phase III trial for patients with breast cancer with newly diagnosed leptomeningeal metastasis. Safety and efficacy of intrathecal administration of new agents such as trastuzumab are under evaluation. Systemic therapy using targeted agents and immunotherapy has also improved outcome in patients with brain metastasis, and its emerging role in the management of leptomeningeal metastasis needs to better studied in prospective series. Focal radiotherapy is commonly indicated for the treatment of macroscopic disease such as meningeal nodules or clinically symptomatic central nervous system structures, for example, base of skull with cranial nerve involvement or cauda equine syndrome. The role of whole brain radiotherapy is decreasing. An individualised combination of different therapeutic options should be used considering the presentation of leptomeningeal metastasis, as well as the histological and molecular tumour characteristics, the presence of concomitant brain and systemic metastases, and prior cancer-directed treatments.

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“…As treatment decisions mainly rely on primary tumor histology, it is essential to determine from which tumor entity LM originated, especially in patients with prior history of 2 or more solid tumors known to evoke LM. This will become increasingly of relevance since novel tumor-specific systemic and intrathecal therapeutics are being designed and studied in phase 1 LM trials (ClinicalTrials.gov Identifier: NCT03025256) [11]. Therefore, it is essential for the treating physician to consider the rare possibility of LM originating from different tumor types in the same patient.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous primary cancer occurrence of melanoma and pulmonary adenocarcinoma in leptomeningeal metastases: a case report

Stoppek¹,

Kebir²,

Junker³

et al. 2019

BMC Cancer

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BackgroundLeptomeningeal metastasis (LM) is a predominantly late stage, devastating complication of a variety of malignant solid tumors. Diagnosis relies predominantly on neurological, radiographic, and cerebrospinal fluid (CSF) assessments. Recently, liquid biopsy tests derived from CSF has shown to be a feasible, noninvasive promising approach to tumor molecular profiling for proper brain cancer diagnostic treatment, thereby providing an opportunity for CSF-based personalized medicine. However, LM is typically misleadingly assumed to originate from only one primary tumor type.Case presentationIn this case report, we provide first evidence of the co-occurrence of LM originating from more than one primary tumor types.Discussion and conclusionsBased on this patient case profile, the co-occurrence of LM from two or more primary tumor types should be accounted for when deriving diagnostic conclusions from liquid biopsy tests.

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Phase I feasibility study for intrathecal administration of trastuzumab in patients with HER2 positive breast carcinomatous meningitis

Cited by 79 publications

References 21 publications

The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers

The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers

How we treat patients with leptomeningeal metastases

Simultaneous primary cancer occurrence of melanoma and pulmonary adenocarcinoma in leptomeningeal metastases: a case report

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