Correlation between tumor growth rate and survival in patients with metastatic breast cancer treated with trastuzumab deruxtecan

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Abstract

Background

Previous studies in multiple metastatic tumors treated with diverse anticancer agents including immunotherapy, chemotherapy, mAb, and TKIs have suggested the rate of tumor growth (g‐score) is inversely associated with survival.

Methods

We performed a retrospective analysis of patients with metastatic breast cancer (mBC) treated with trastuzumab deruxtecan (T‐DXd), ado‐trastuzumab emtansine (T‐DM1), or chemotherapy to investigate the impact of those therapies on g‐score and explore the association of g‐score with clinical outcomes. This is the first report assessing g‐score in tumors treated with an ADC.

Results

We investigated the association of g‐score with progression‐free (PFS) and overall survival (OS) in 2 phase 3 studies in patients with HER2 + mBC (DESTINY‐Breast03 (DB-03)) and HER2‐low mBC (DESTINY‐Breast04 (DB-04)). After grouping patients according to quartiles of g‐scores, we explored the association between g‐score and PFS/OS using Kaplan‐Meier plots and Cox regression models. The median g‐score was higher for T‐DM1, suggesting a faster growth rate at 0.0009/day vs that for T‐DXd at 0.0002/day ( P < .0001). Additionally, with data collection stopped at the time of database lock, 23% and 48% of tumors demonstrated only regression without growth in the T‐DM1 and T‐DXd arms, respectively. In DB-04, median g was 0.0018/day and 0.0006/day ( P < .0001); with 17% and 32% of tumors demonstrating only regression with treatment of physician’s choice (TPC) and T‐DXd, respectively.

Conclusions

Compared to T‐DM1 and TPC therapies, T‐DXd significantly reduced the rate of tumor growth in the overall population and across subgroups. In both studies, the tumor growth rate was inversely associated with PFS and OS. In addition, it showed improved concordance with survival compared to ORR. The use of tumor growth rate as an intermediate endpoint may potentially accelerate drug development and reduce a patient’s exposure to agents with limited or no activity.

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Author and article information

Contributors

Philip He:

ORCID: https://orcid.org/0000-0001-6804-1501

Dhiraj Gambhire

Haiming Zhou

Xiaoyang Ma: Role: Data curation

Yoshihiro Emura

Abderrahmane Laadem

David Leung

Susan Bates

Antonio Tito Fojo

Olivier Rixe

Journal

Journal ID (nlm-ta): Oncologist

Journal ID (iso-abbrev): Oncologist

Journal ID (publisher-id): oncolo

Title: The Oncologist

Publisher: Oxford University Press (US )

ISSN (Print): 1083-7159

ISSN (Electronic): 1549-490X

Publication date Collection: May 2025

Publication date (Electronic): 11 May 2025

Publication date PMC-release: 11 May 2025

Volume: 30

Issue: 5

Electronic Location Identifier: oyaf057

Affiliations

Daiichi Sankyo Inc. , Basking Ridge, NJ, United States

Herbert Irving Comprehensive Cancer Center, Columbia University , New York, NY, United States

James J Peters VA Medical Center , Bronx, NY, United States

Herbert Irving Comprehensive Cancer Center, Columbia University , New York, NY, United States

James J Peters VA Medical Center , Bronx, NY, United States

Daiichi Sankyo Inc. , Basking Ridge, NJ, United States

Author notes

Corresponding author: Philip He, Biostatistics, Daiichi Sankyo Inc., 211 Mt Airy Road, Basking Ridge, NJ 07920, USA ( philipyihe2018@ 123456gmail.com ).

Author information

Philip He https://orcid.org/0000-0001-6804-1501

Article

Publisher ID: oyaf057

DOI: 10.1093/oncolo/oyaf057

PMC ID: 12065935

PubMed ID: 40349141

SO-VID: 3251bc8a-02c9-43a2-a124-0c5de8d16456

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 22 December 2024

Date accepted : 26 February 2025

Page count

Pages: 10

Funding

Funded by: Daiichi Sankyo, Inc;

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