Charting the Course in Sequencing Antibody-Drug Conjugates in Breast Cancer
Giuseppe Saltalamacchia1, Rosalba Torrisi1, Rita De Sanctis1,2
1IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, 20089 Rozzano, MI, Italy.
Abstract:
Based on the unprecedented results observed in recent clinical trials, antibody-drug conjugates (ADCs) have revolutionized the treatment algorithm of metastatic breast cancer (mBC). The strategy of sequencing different ADCs in other lines of therapy is highly attractive, but the proportion of patients who have undergone such a strategy in the context of published clinical trials is still limited, especially for modern ADCs. HER2-positive disease is primarily managed with a sequence of different ADCs. Historically, trastuzumab emtansine (T-DM1) has been the most commonly used ADC for both early and metastatic HER2-positive disease. Considering the recent evidence related to trastuzumab deruxtecan (T-DXd), it is expected to assume the role of the main ADC in our clinical practice. Herein, we report a retrospective analysis of the sequence of different ADCs relying on available published data from clinical trials.
Insights
Antibody-drug conjugates (ADCs) have transformed metastatic breast cancer treatment. This study retrospectively analyzes sequencing different ADCs in clinical trials, focusing on HER2-positive disease and emerging therapies like trastuzumab deruxtecan (T-DXd).
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Antibody-drug conjugates (ADCs) represent a significant advancement in metastatic breast cancer (mBC) treatment.
- Sequencing different ADCs is a promising therapeutic strategy, but data from clinical trials remain limited, particularly for newer agents.
- HER2-positive breast cancer management heavily relies on sequential ADC therapy, with trastuzumab emtansine (T-DM1) historically dominating.
Purpose of the Study:
- To retrospectively analyze the sequence of different antibody-drug conjugates (ADCs) used in metastatic breast cancer treatment.
- To evaluate the current landscape of ADC sequencing based on available published clinical trial data.
- To assess the evolving role of ADCs, including trastuzumab deruxtecan (T-DXd), in HER2-positive mBC management.
Main Methods:
- Retrospective analysis of published clinical trial data.
- Focus on treatment sequences involving various antibody-drug conjugates (ADCs).
- Inclusion of data pertaining to HER2-positive metastatic breast cancer.
Main Results:
- Limited patient data exists on sequential ADC strategies within published clinical trials.
- Trastuzumab emtansine (T-DM1) has been the predominant ADC in HER2-positive disease.
- Trastuzumab deruxtecan (T-DXd) is emerging as a key ADC, likely to become central in clinical practice.
Conclusions:
- The sequencing of antibody-drug conjugates (ADCs) is a critical aspect of modern metastatic breast cancer therapy.
- Further clinical data is needed to fully understand the optimal sequencing of ADCs, especially newer agents like T-DXd.
- The role of ADCs in HER2-positive mBC is evolving, with T-DXd poised to become a frontline treatment.
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