Anlotinib-based Combination Therapy in Patients with Hormone Receptor-positive（HR+） Metastatic Breast Cancer(MBC) .

A New Option for Post-CDK4/6is Resistance Era: Multicenter Real-world Study of Anlotinib-based Combination Therapy in Hormone Receptor-positive Metastatic Breast Cancer Resistant to CDK4/6is.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors combined with hormonal therapy are the current standard frontline treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER-2)-negative metastatic breast cancer (MBC). However, the optimal treatment after progression on CDK4/6 inhibitors remains unknown. Anlotinib is an oral multi-target tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. This study aimed to evaluate the safety and efficacy of anlotinib-based combination therapy in patients with HR+ MBC previously treated with a CDK4/6 inhibitor.

Study Overview

• Status: Recruiting
• Conditions: HR+ Breast Cancer
• Intervention / Treatment: Other: Anlotinib+eribulin/nab-paclitaxel/etoposide/capecitabine/pembrolizumab/ sintilimab/ fulvestrant, etc

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Quchang Ouyang; Phone Number: 15676789890; Email: tgzybc@163.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Provincial Tumor Hospital
      • Contact: Li; Phone Number: 15616453102; Email: tgzybc@163.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

HR+ metastatic breast cancer previously treated with CDK4/6is

Description

Inclusion Criteria:

• Female patients aged 18 to 75 years, with an ECOG score of 0-1, and an expected survival of at least 3 months;
• Presence of measurable lesions as defined by RECIST 1.1 criteria;
• Histopathologically confirmed HR-positive/HER2-negative breast cancer. HER2 negativity is determined by an immunohistochemistry (IHC) result of HER2 (0/1+). If the result is HER2 (++), a FISH or CISH test is required to confirm the absence of HER2 amplification;
• Patients who have undergone multiple lines of advanced therapy with no remaining standard treatment options;
• Prior treatment with at least one line of CDK4/6 inhibitors and endocrine therapy;
• Disease progression following aromatase inhibitor (AI) or fulvestrant combined with CDK4/6 inhibitors, either as adjuvant therapy or as systemic treatment for advanced disease.

Exclusion Criteria:

• Patients with HER2-positive breast cancer confirmed by histology or cytology;
• Patients who discontinued therapy due to non-disease progression reasons, such as adverse events or other non-medical factors;
• Detection of a second primary malignant tumor at the time of enrollment;
• Failure to complete CDK4/6 inhibitor therapy;
• Pregnant or breastfeeding patients;
• Presence of third-space fluid accumulation (e.g., pleural effusion, ascites, pericardial effusion) that cannot be managed through drainage or other methods;
• Patients previously treated with anti-angiogenic agents, including small molecules such as anlotinib or apatinib, and large molecules such as bevacizumab;
• Patients currently receiving any other anti-tumor treatment for any other malignancies.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Progression-free survival estimated using Kaplan-Meier methods is defined as the time from the date of informed consent to the earlier of death or disease progression. Patients alive without disease progression are censored at the date of last disease evaluation. Progressive disease (PD) based on RECIST 1.1 is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Equivocal progression of non-target lesions also qualifies as PD.	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	The ORR will be defined as the proportion of patients in the Efficacy Evaluable patient Set who achieve complete response (CR) and partial response (PR)	through study completion, an average of 1 year
Disease control rate (DCR)	The DCR will be defined as the proportion of patients in the Efficacy Evaluable patient Set who achieve complete response (CR) or partial response (PR) or stable disease (SD).	through study completion, an average of 1 year
Overall survival(OS)	OS, defined as the time from the date of informed consent until to the date of death, regardless of the cause of death.	through study completion, an average of 5 year
Incidence of Treatment-Emergent Adverse Events (Safety)	All the treatment-related adverse events occurred as assessed by CTCAE v4.0	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 5, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: November 3, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormone Antagonists; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Estrogen Receptor Antagonists; Estrogen Antagonists; Capecitabine; Fulvestrant; Etoposide; Pembrolizumab; Paclitaxel
• Other Study ID Numbers: ALTER-BC-005

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No