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Observational Study
. 2025 Sep 1;30(9):oyaf229.
doi: 10.1093/oncolo/oyaf229.

Breast CancerTrastuzumab-deruxtecan and radiotherapy: a safety sub-analysis of combart prospective cohort study

Edy Ippolito  1   2 , Martina Benincasa  1 , Francesco Pantano  3   4 , Carlo Greco  1   2 , Marco Donato  4 , Carla Maria Gullotta  4 , Lucrezia Toppi  2 , Rita Alaimo  2 , Paola Martucci  2 , Guenda Meffe  2 , Michele Fiore  1   2 , Giuseppe Tonini  3   4 , Rolando Maria D'Angelillo  5 , Sara Ramella  1   2
Affiliations
Observational Study

Breast CancerTrastuzumab-deruxtecan and radiotherapy: a safety sub-analysis of combart prospective cohort study

Edy Ippolito et al. Oncologist. .

Abstract

Aim: This observational analysis, derived from the prospective mono-institutional COMBART cohort (stage IV breast cancer patients undergoing radiation therapy during novel systemic treatments), evaluates the safety of combining radiotherapy (RT) with Trastuzumab Deruxtecan (T-DXd) in metastatic breast cancer patients.

Material and methods: Patients eligible for this analysis received conventional RT or stereotactic radiotherapy (SRT) concurrently with T-DXd. RT was considered concurrent if administered on the same day as T-DXd or during the 3-week interval between cycles. T-DXd was given at a dose of 5.4 mg kg-1 via intravenous infusion every 3 weeks until progression or unacceptable toxicity. The primary endpoint was to assess RT-related acute and late toxicities, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

Results: Forty patients who underwent RT or SRT concurrently with T-DXd were selected from the cohort of 145 patients enrolled in the COMBART trial. A total of 98 lesions were treated. Palliative RT was performed in 50.0% of patients, while 50.0% underwent SRT. Acute toxicity of any grade was observed in 8/40 patients (20.0%) during RT. One patient developed grade 3 anemia (3.3%), leading to RT discontinuation. Late toxicity occurred in 4/40 patients (10%) consisting of 3 radiation pneumonitis (RP) and 3 radionecrosis. Among the 22 patients treated with SBRT for oligoprogressive disease, the time from the initiation of RT to second disease progression (progression-free survival 2 -PFS2) was 11.3 months (95% CI, 4.61-25.82), and the median time to systemic treatment change was 19.1 months (95% CI, 12.7-25.56).

Conclusions: The safety data for concurrent RT and T-DXd are promising. Most non-hematologic toxicities appear to be related to RT, while hematologic toxicities are likely influenced by T-DXd and should be closely monitored.

Keywords: Trastuzumab-Deruxtecan; breast cancer; radiotherapy; safety.

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Conflict of interest statement

E.I.: Speaking fees: Astrazeneca, Amgen, MSD; Francesco Pantano: Advisory Board relationship: Astrazeneca; G.T.: Advisory Board relationship: Astrazeneca; S.R.: Consulting/Advisory board: Astrazeneca; Speaking fees: Astrazeneca, Amgen, Roche, MSD; Research funding: Astrazeneca, Roche, MSD: R.M.D.: Consulting/Advisory board: Astellas Pharma, Bayer, Ferring, Ipsen, Johnson and Johnson; Research Funding: Johnson and Johnson. The other authors report no conflict of interest.

References

    1. Tamura K, Tsurutani J, Takahashi S, et al. Trastuzumab deruxtecan (DS- 8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019;20:816-826. - PubMed
    1. Enhertu (fam-trastuzumab deruxtecan-nxki) for injection, for intravenous use. Prescribing information. Basking Ridge (NJ): Daiichi Sankyo, Inc.; 2022. Available from: https://daiichisankyo.us/prescribing-information-portlet/getPIContent? p.... [Google Scholar]
    1. Modi S, Saura C, Yamashita T, et al. DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621. - PMC - PubMed
    1. Nakada T, Sugihara K, Jikoh T, Abe Y, Agatsuma T. The latest research and development into the antibody-drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy. Chem Pharm Bull (Tokyo). 2019;67:173-185. - PubMed
    1. Ogitani Y, Aida T, Hagihara K, et al. DS-8201a, a novel HER2-­targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res. 2016;22:5097-5108. - PubMed

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