Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer

Yoshino, T. (Takayuki); Di-Bartolomeo, M. (Maria); Raghav, K. (Kanwal); Masuishi, T. (Toshiki); Loupakis, F. (Fotios); Kawakami, H. (Hisato); Yamaguchi, K. (Kensei); Nishina, T. (Tomohiro); Wainberg, Z. (Zev); Elez, E. (Elena); Rodríguez-Rodríguez, J. (Javier); Fakih, M. (Marwan); Ciardiello, F. (Fortunato); Saxena, F. (Kapil); Kobayashi, K. (Kojiro); Bako, E. (Emarjola); Okuda, Y. (Yasuyuki); Meinhardt, G. (Gerold); Grothey, A. (Axel); Siena, S. (Salvatore)

Keywords:

Área de Medicina Clínica y Epidemiología
Trastuzumab deruxtecan (T-DXd)
Metastatic colorectal cancer (mCRC)
Objective response rate (ORR)

Issue Date:

2023

Publisher Version:

https://pubmed.ncbi.nlm.nih.gov/37286557/

ISSN:

2041-1723

Note:

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.

Citation:

Yoshino, T.; Di Bartolomeo, M.; Raghav, K.; et al. "Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer". Nature communications. 14 (1), 2023, 3332

Abstract

DESTINY-CRC01 (NCT03384940) was a multicenter, open-label, phase 2 trial assessing the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-expressing metastatic colorectal cancer (mCRC) that progressed after >= 2 prior regimens; results of the primary analysis are published. Patients received T-DXd 6.4mg/kg every 3 weeks and were assigned to either: cohort A (HER2-positive, immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+), cohort B (IHC 2+/ISH-), or cohort C (IHC 1+). Primary endpoint was objective response rate (ORR) by independent central review in cohort A. Secondary endpoints included ORR (cohorts B and C), duration of response, disease control rate, progression-free survival, overall survival, pharmacokinetics, and safety of T-DXd. 86 patients were enrolled (53 in cohort A, 15 in cohort B, and 18 in cohort C). Results of the primary analysis are published, reporting an ORR of 45.3% in cohort A. Here, we report the final results. No responses occurred in cohorts B or C. Median progression-free survival, overall survival, and duration of response were 6.9, 15.5, and 7.0 months, respectively. Overall serum exposure (cycle 1) of T-DXd, total anti-HER2 antibody, and DXd were similar regardless of HER2 status. Most common grade >= 3 treatment-emergent adverse events were decreased neutrophil count and anemia. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 8 patients (9.3%). These findings support the continued exploration of T-DXd in HER2-positive mCRC.

URI:

https://hdl.handle.net/10171/67553

DOI:

10.1038/s41467-023-38032-4

Appears in Collections:

DA - CUN - Oncología médica - Capítulos de libros

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