This study aims to evaluate whether the combination of Megestrol Acetate at the initiation of Trastuzumab Deruxtecan (T-DXd) treatment can effectively prevent and alleviate T-DXd-related fatigue, thereby improving the quality of life for advanced breast cancer patients.
Female, aged 18-75 years
Pathologically confirmed inoperable or metastatic breast cancer with complete ER, PR, and HER2 status
HER2-positive (IHC 3+ or IHC 2+ with FISH positive), HER2-low (IHC 1+ or IHC 2+ with FISH negative), or HER2-ultralow (IHC 0 with ≤10% weak incomplete membrane staining) [most recent specimen used]
Investigator-assessed indication for Trastuzumab Deruxtecan (T-DXd) therapy
Severe underlying disease, comorbidities, active infection, or severe metabolic disorders
Clinically significant severe fatigue at baseline (FACIT-F score <30)
Currently receiving other antitumor therapies
Pregnant or lactating patients
Parallel
Megestrol Acetate + Trastuzumab Deruxtecan
DrugMegestrol Acetate 160mg orally, days 1-5, every 3 weeks for 2 cycles; Combined with standard Trastuzumab Deruxtecan 5.4 mg/kg IV infusion every 3 weeks
Placebo + Trastuzumab Deruxtecan
DrugMatched placebo 160mg orally, days 1-5, every 3 weeks for 2 cycles; Combined with standard Trastuzumab Deruxtecan 5.4 mg/kg IV infusion every 3 weeks
Change in Fatigue Score (FACIT-Fatigue Scale)
Measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Scale Version 4. Total score range: 0-52, with higher scores indicating less fatigue and better quality of life.
Change in Brief Fatigue Inventory (BFI) Score
The Brief Fatigue Inventory (BFI) is a self-reported instrument designed to assess the severity and impact of cancer-related fatigue. It consists of 9 items: 3 items assess fatigue severity at its "worst," "usual," and "current" states over the past 24 hours. 1）6 items assess the degree to which fatigue interferes with daily activities (general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life). 2）Scoring Criteria: Each item is rated on a 0 to 10 numerical scale, where 0 represents "no fatigue" or "does not interfere" and 10 represents "as bad as you can imagine" or "completely interferes." The total score is calculated as the average of the 9 items (range: 0-10). Mild fatigue: 1 to 3 Moderate fatigue: 4 to 6 Severe fatigue: 7 to 10 Higher scores indicate greater fatigue severity and functional impairment.
Objective Response Rate (ORR)
Including Complete Response (CR) and Partial Response (PR) per RECIST 1.1 criteria
Patient Reported Outcomes (PRO)
EORTC QLQ-C30 is a 30-item questionnaire used to assess the quality of life of cancer patients. It includes: 5 Functional Scales: Physical, role, cognitive, emotional, and social functioning. 3 Symptom Scales: Fatigue, pain, and nausea/vomiting. A Global Health Status/Quality of Life (GHS/QoL) scale. 6 Single Items: Dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficultie EORTC QLQ-BR45 is a 45-item breast cancer-specific module used to assess quality of life. It consists of functional scales (e.g., body image, sexual functioning, breast satisfaction) and symptom scales (e.g., systemic therapy side effects, upset by hair loss, arm/breast symptoms, and skin/mucosal reactions to targeted therapies). Scores are linearly transformed to a range of 0 to 100. For functional scales, a higher score represents a higher level of functioning/better quality of life. For symptom scales, a higher score represents a greater symptom burden or more severe side effects
Safety and Tolerability
1\. Incidence of Adverse Events (AEs) graded by CTCAE v5.0
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