Tucatinib Combination Treatment After Trastuzumab-Deruxtecan in Patients With ERBB2-Positive Metastatic Breast Cancer.

Autor:	Frenel JS; Department of Medical Oncology, Institut de Cancerologie de l'Ouest, Saint-Herblain, France., Zeghondy J; Department of Medical Oncology, Gustave Roussy Cancer Center, Villejuif, France., Guérin-Charbonnel C; Department of Biostatistics and Analytics, Institut de Cancerologie de l'Ouest, Saint-Herblain, France., Mailliez A; Department of Medical Oncology, Oscar Lambret Comprehensive Cancer Center, Lille, France., Volant E; Department of Medical Oncology, Institut de Cancerologie de l'Ouest, Saint-Herblain, France., Poumeaud F; Department of Medical Oncology, Oncopôle, Toulouse, France., Patsouris A; Department of Medical Oncology, Institut de Cancerologie de l'Ouest, Angers, France., Arnedos M; Department of Medical Oncology Bordeaux, Institut Bergonie, Bordeaux, France., Bailleux C; Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France., Cabal J; Department of Medical Oncology, Centre Eugene Marquis, Rennes, France., Galland L; Department of Medical Oncology, Centre Georges Francois Leclerc, Dijon, France., de Nonneville A; Department of Medical Oncology, Institut Paoli Calmette, Marseille, France., Guiu S; Department of Medical Oncology, Montpellier Cancer Institute, Montpellier, France., Dalenc F; Department of Medical Oncology, Oncopôle, Toulouse, France., Pistilli B; Department of Medical Oncology, Gustave Roussy Cancer Center, Villejuif, France., Bachelot T; Department of Medical Oncology, Centre Léon Bérard, Lyon, France., Pierga JY; Department of Medical Oncology, Institut Curie, Paris, France., Le Du F; Department of Medical Oncology, Centre Eugene Marquis, Rennes, France., Bocquet F; Data Factory, Institut de Cancerologie de l'Ouest, Saint-Herblain, France., Larrouquere L; Department of Medical Oncology, Centre Léon Bérard, Lyon, France., Loirat D; Department of Medical Oncology, Institut Curie, Paris, France.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2024 Apr 01; Vol. 7 (4), pp. e244435. Date of Electronic Publication: 2024 Apr 01.
DOI:	10.1001/jamanetworkopen.2024.4435
Abstrakt:	Importance: Little is known regarding the outcomes associated with tucatinib combined with trastuzumab and capecitabine (TTC) after trastuzumab-deruxtecan exposure among patients with ERBB2 (previously HER2)-positive metastatic breast cancer (MBC). Objective: To investigate outcomes following TTC treatment in patients with ERBB2-positive MBC who had previously received trastuzumab-deruxtecan. Design, Setting, and Participants: This cohort study included all patients with MBC who were treated in 12 French comprehensive cancer centers between August 1, 2020, and December 31, 2022. Exposure: Tucatinib combined with trastuzumab and capecitabine administered at the recommended dose. Main Outcomes and Measures: Clinical end points included progression-free survival (PFS), time to next treatment (TTNT), overall survival (OS), and overall response rate (ORR). Results: A total of 101 patients with MBC were included (median age, 56 [range, 31-85] years). The median number of prior treatment lines for metastatic disease at TTC treatment initiation was 4 (range, 2-15), including 82 patients (81.2%) with previous trastuzumab and/or pertuzumab and 94 (93.1%) with previous ado-trastuzumab-emtansine) exposure. The median duration of trastuzumab-deruxtecan treatment was 8.9 (range, 1.4-25.8) months, and 82 patients (81.2%) had disease progression during trastuzumab-deruxtecan treatment, whereas 18 (17.8%) had stopped trastuzumab-deruxtecan for toxic effects and 1 (1.0%) for other reasons. Tucatinib combined with trastuzumab and capecitabine was provided as a third- or fourth-line treatment in 37 patients (36.6%) and was the immediate treatment after trastuzumab-deruxtecan in 86 (85.1%). With a median follow-up of 11.6 (95% CI, 10.5-13.4) months, 76 of 101 patients (75.2%) stopped TTC treatment due to disease progression. The median PFS was 4.7 (95% CI, 3.9-5.6) months; median TTNT, 5.2 (95% CI, 4.5-7.0) months; and median OS, 13.4 (95% CI, 11.1 to not reached [NR]) months. Patients who received TTC immediately after trastuzumab-deruxtecan had a median PFS of 5.0 (95% CI, 4.2-6.0) months; median TTNT of 5.5 (95% CI, 4.8-7.2) months, and median OS of 13.4 (95% CI, 11.9-NR) months. Those who received TTC due to trastuzumab-deruxtecan toxicity-related discontinuation had a median PFS of 7.3 (95% CI, 3.0-NR) months. Best ORR was 29 of 89 patients (32.6%). Sixteen patients with active brain metastasis had a median PFS of 4.7 (95% CI, 3.0-7.3) months, median TTNT of 5.6 (95% CI, 4.4 to NR), and median OS of 12.4 (95% CI, 8.3-NR) months. Conclusions and Relevance: In this study, TTC therapy was associated with clinically meaningful outcomes in patients with ERBB2-positive MBC after previous trastuzumab-deruxtecan treatment, including those with brain metastases. Prospective data on optimal drug sequencing in this rapidly changing therapeutic landscape are needed.
Databáze:	MEDLINE
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