Real-World Treatment of ADC-Resistant HER2-Low Advanced Breast Cancer

Optimal Treatment Strategies for ADC-Resistant HER2-Low Advanced Breast Cancer: A Multicenter, Retrospective Real-World Study

This is a multicenter, retrospective real-world study aiming to evaluate the efficacy and safety of post-antibody-drug conjugate (post-ADC) treatment strategies in patients with HER2-low advanced breast cancer who have developed resistance to prior ADC therapy. The study plans to enroll approximately 220 eligible patients from three centers in China (Jiangsu Province Hospital, Nanjing Drum Tower Hospital, and Nanjing General Hospital of Nanjing Military Command) between January 2018 and December 2025. Key efficacy outcomes include progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Safety outcomes include the incidence of grade 3/4 adverse events and serious adverse events. Subgroup analyses will compare different post-ADC regimens (e.g., alternative ADC, chemotherapy, endocrine therapy, immunotherapy) and explore the impact of visceral metastasis and prior ADC treatment response on subsequent outcomes. This study seeks to identify optimal post-ADC treatment strategies and preferred patient populations for clinical benefit.

Study Overview

• Status: Completed
• Conditions: Breast Cancer

• Study Type: Observational
• Enrollment (Actual): 220

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • The First Affiliated Hospital with Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with histologically confirmed HER2-low advanced or metastatic breast cancer who received antibody-drug conjugate (ADC) therapy in the advanced setting and subsequently experienced disease progression.

Description

Inclusion Criteria:

• females aged ≥18 years.
• confirmed pathologic diagnosis of HER2-low MBC (defined as HER2 IHC 1+ or 2+ without gene amplification by FISH detection).
• patients had disease progression following ADC treatment in advanced setting and had undergone at least one available efficacy evaluation.
• patients received at least one subsequent anti-tumor treatment following ADC failure, with at least one available efficacy evaluation.

Exclusion Criteria:

• patients previously treated with ADC during neoadjuvant or adjuvant setting.
• patients who had not experienced disease progression on their first ADC (ADC1) regimen and remained on ADC1 treatment.
• patients with no documented subsequent anti-tumor therapy following ADC1 treatment.
• patients who lacked evaluable efficacy assessment data during ADC1 or post-ADC therapy.
• patients with incomplete clinicopathological information.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
real-world (rwPFS) of post-ADC therapy	the duration from the post-ADC treatment initiation to either disease progression or death from any cause, whichever came first	up to 12 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR)	ORR was defined as the percentage of patients achieving a best overall response of complete response (CR) or partial response (PR).	at 12 weeks
Clinical benefit rate (CBR) of post-ADC therapy	CBR was determined by the percentage of patients achieving disease control, defined as complete response (CR), partial response (PR), or stable disease (SD).	at 12 weeks
overall survival (OS) of post-ADC therapy	Overall survival was defined as the duration from post-ADC treatment initiation to death from any cause.	up to 24 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: May 8, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 2026-SR-247