Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: the DEBBRAH trial

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• dc.contributor.author Pérez-García, José Manuel
• dc.contributor.author Vaz Batista, Marta
• dc.contributor.author Cortez, Patricia
• dc.contributor.author Ruiz-Borrego, Manuel
• dc.contributor.author Cejalvo, Juan Miguel
• dc.contributor.author de la Haba-Rodríguez, Juan
• dc.contributor.author Garrigós, Laia
• dc.contributor.author Racca,Fabricio
• dc.contributor.author Servitja Tormo, Sonia
• dc.contributor.author Blanch, Salvador
• dc.contributor.author Gion, María
• dc.contributor.author Nave, Monica
• dc.contributor.author Fernández-Abad, María
• dc.contributor.author Martínez-Bueno, Alejandro
• dc.contributor.author Llombart-Cussac, Antonio
• dc.contributor.author Sampayo-Cordero, Miguel
• dc.contributor.author Malfettone, Andrea
• dc.contributor.author Cortés, Javier
• dc.contributor.author Braga, Sofía
• dc.date.accessioned 2022-11-28T07:57:31Z
• dc.date.issued 2023
• dc.description.abstract Background: trastuzumab deruxtecan (T-DXd) has shown durable antitumor activity in pretreated patients with HER2-positive advanced breast cancer (ABC), but its efficacy has not yet been evaluated in patients with active brain metastases (BMs). DEBBRAH aims to assess T-DXd in patients with HER2-positive or HER2-low ABC and central nervous system involvement. Methods: this ongoing, five-cohort, phase II study (NCT04420598) enrolled patients with pretreated HER2-positive or HER2-low ABC with stable, untreated, or progressing BMs and/or leptomeningeal carcinomatosis. Here, we report findings from HER2-positive ABC patients with non-progressing BMs after local therapy (n=8; cohort 1), asymptomatic untreated BMs (n=4; cohort 2), or progressing BMs after local therapy (n=9; cohort 3). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was 16-week progression-free survival (PFS) for cohort 1 and intracranial overall response rate (ORR-IC) for cohorts 2 and 3. Results: as of October 20, 2021, 21 patients received T-DXd. In cohort 1, 16-week PFS rate was 87.5% (95%CI, 47.3-99.7; P<.001). ORR-IC was 50.0% (95%CI, 6.7-93.2) in cohort 2 and 44.4% (95%CI, 13.7-78.8; P<.001) in cohort 3. Overall, the ORR-IC in patients with active BMs was 46.2% (95%CI, 19.2-74.9). Among patients with measurable intracranial or extracranial lesions at baseline, the ORR was 66.7% (12 out of 18 patients; 95%CI, 41.0-86.7), 80.0% (95%CI, 28.4-99.5) in cohort 1, 50.0% (95%CI, 6.7-93.2) in cohort 2, and 66.7% (95%CI, 29.9-92.5) in cohort 3. All responders had partial responses. The most common adverse events included fatigue (52.4%; 4.8% grade≥3), nausea (42.9%; 0% grade≥3), neutropenia (28.6%; 19% grade≥3), and constipation (28.6%; 0% grade≥3). Two (9.5%) patients suffered grade 1 interstitial lung disease/pneumonitis. Conclusions: T-DXd showed intracranial activity with manageable toxicity and maintained quality of life in pretreated HER2-positive ABC patients with stable, untreated, or progressing BMs. Further studies are needed to validate these results in larger cohorts.
• dc.format.mimetype application/pdf
• dc.identifier.citation Pérez-García JM, Batista MV, Cortez P, Ruiz-Borrego M, Cejalvo JM, de la Haba-Rodriguez J, et al. Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: the DEBBRAH trial. Neuro Oncol. 2023 Jan 5; 25(1): 157-66. DOI: 10.1093/neuonc/noac144
• dc.identifier.doi http://dx.doi.org/10.1093/neuonc/noac144
• dc.identifier.issn 1522-8517
• dc.identifier.uri http://hdl.handle.net/10230/55011
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.rights © Oxford University Press. This is a pre-copyedited, author-produced version of an article accepted for publication in Neuro-oncology following peer review. The version of record Pérez-García JM, Batista MV, Cortez P, Ruiz-Borrego M, Cejalvo JM, de la Haba-Rodriguez J, et al. Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: the DEBBRAH trial. Neuro Oncol. 2022 May 26: noac144. is available online at: https://academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noac144/6593857.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword HER2-positive
• dc.subject.keyword T-DXd
• dc.subject.keyword Trastuzumab deruxtecan
• dc.subject.keyword Advanced breast cancer
• dc.subject.keyword Brain metastases
• dc.title Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: the DEBBRAH trial
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion