Intrathecal trastuzumab versus alternate routes of delivery for HER2-targeted therapies in patients with HER2+ breast cancer leptomeningeal metastases

Lazaratos, Anna-Maria; Maritan, Sarah M.; Quaiattini, Andrea; Darlix, Amélie; Ratoša, Ivica; Ferraro, Emanuela; Griguolo, Gaia; Guarneri, Valentina; Pellerino, Alessia; Höfer, Silvia; Jacot, William; Stemmler, Hans-Joachim; Broek, Marcel P. H. van den; Dobnikar, Nika; Panet, François; Lahijanian, Zubin; Morikawa, Aki; Seidman, Andrew D.; Soffietti, Riccardo; Panasci, Lawrence C.; Petrecca, Kevin; Rose, April A.N.; Bouganim, Nathaniel; Dankner, Matthew

doi:10.1016/j.breast.2023.04.008

Cited by 9 publications

(5 citation statements)

References 38 publications

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“… 57 In humans, intrathecal delivery of trastuzumab (anti-HER2) has been tested against leptomeningeal disease, and rituximab (anti-CD20) for recurrent CNS lymphoma. 58 , 59 Unfortunately, the apparent CSF half-life of trastuzumab is only 4.1 ± 3.0 h, and also for rituximab, CSF concentration in these studies dropped to approximately 5% of the initial dose within three days post-application. 58 , 60 …”

Section: Strategies To Increase Antibody Delivery To the Brainmentioning

confidence: 74%

Exit pathways of therapeutic antibodies from the brain and retention strategies

Schellhammer,

Beffinger,

Salazar

et al. 2023

iScience

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Section: Strategies To Increase Antibody Delivery To the Brainmentioning

confidence: 74%

Exit pathways of therapeutic antibodies from the brain and retention strategies

Schellhammer,

Beffinger,

Salazar

et al. 2023

iScience

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“…A study is considered to be of good quality (i.e., low risk of bias) if it meets all five criteria, of moderate quality if it meets four criteria, and of poor quality (high risk of bias) if it meets three or fewer criteria ( Supplemental Fig. S1 ) [ 38 , 39 ].…”

Section: Methodsmentioning

confidence: 99%

Osimertinib is associated with improved outcomes in pre-treated non-small cell lung cancer leptomeningeal metastases: A systematic review and meta-analysis

Bian,

Lazaratos,

Maritan

et al. 2024

Heliyon

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“…To assess the methodological quality of individual studies included in the systematic review, we used a previously described tool that is adapted for evaluation of case reports and case series 31,32 . The tool includes 5 items that are derived from the Newcastle-Ottawa scale 33 .…”

Section: Quality Assessmentmentioning

confidence: 99%

Clinical activity of Mitogen-Activated Protein Kinase (MAPK) inhibitors in patients with MAP2K1 (MEK1)-mutated metastatic cancers

Dankner,

Rousselle,

Petrecca

et al. 2024

Preprint

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PURPOSEMAP2K1/MEK1 mutations are potentially actionable drivers in cancer. MAP2K1 mutations have been functionally classified into three groups according to their dependency on upstream RAS/RAF signaling. However, the clinical efficacy of MAPK pathway inhibitors (MAPKi) for MAP2K1 mutant tumors is not well defined. We sought to characterize the genomic and clinical landscape of MAP2K1 mutant tumors to evaluate the relationship between MAP2K1 mutation Class and clinical activity of MAPKi.METHODSWe interrogated AACR GENIE (v13) to analyze solid tumors with MAP2K1 mutations. We performed a systematic review and meta-analysis of published reports of patients with MAP2K1 mutant cancers treated with MAPKi according to PRISMA guidelines. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall response rate (ORR), duration of response (DOR), and overall survival (OS).RESULTSIn the AACR GENIE dataset, Class 2 MAP2K1 mutations (63%) were more prevalent than Class 1 (24%) and Class 3 (13%) mutations (P<0.0001). Co-occurring MAPK pathway activating mutations were more likely to occur in Class 1 versus Class 2 or 3 MAP2K1 mutant tumors (P<0.0001). Our systematic meta-analysis of the literature identified 46 patients with MAP2K1 mutant tumors who received MAPKi. In these patients, ORR was 28% and median PFS was 3.9 months. ORR did not differ according to MAP2K1 mutation class or cancer type. However, patients with Class 2 mutations experienced longer PFS (5.0 months) and DOR (23.8 months) compared to patients with Class 1, 3 or unclassified MAP2K1 mutations (PFS 3.5 months, P=0.04; DOR 4.2 months, P=0.02).CONCLUSIONPatients with Class 2 MAP2K1 mutations represent a novel subgroup that may derive benefit from MAPKi. Prospective clinical studies with novel MAPKi regimens are warranted in these patients.Highlights- A meta-analysis describing clinical outcomes with MAPK targeted therapy in MAP2K1 mutant tumors.- Clinical validation of MAP2K1 mutation Class as a predictive biomarker.- Class 2 MAP2K1 mutations are sensitive to MEK-inhibitor containing regimens.Graphical Abstract

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Intrathecal trastuzumab versus alternate routes of delivery for HER2-targeted therapies in patients with HER2+ breast cancer leptomeningeal metastases

Cited by 9 publications

References 38 publications

Exit pathways of therapeutic antibodies from the brain and retention strategies

Exit pathways of therapeutic antibodies from the brain and retention strategies

Osimertinib is associated with improved outcomes in pre-treated non-small cell lung cancer leptomeningeal metastases: A systematic review and meta-analysis

Clinical activity of Mitogen-Activated Protein Kinase (MAPK) inhibitors in patients with MAP2K1 (MEK1)-mutated metastatic cancers

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