Stereotactic Ablative Body Radiotherapy (SABR) with Maintenance of Systemic Therapy Versus Physicians' Choice of Systemic Therapy for Oligoprogressive ER-positive, Her-2 Negative Breast Cancer II

Launched by PETER MACCALLUM CANCER CENTRE, AUSTRALIA · Mar 12, 2025

Keywords

ClinConnect Summary

AVATAR II is a phase II multicentre open label, randomised trial. Following informed consent, eligible patients with ER-positive, HER2-negative advanced breast cancer receiving an ET (either AI or selective estrogen receptor degrader in combination with a CDK 4/6 inhibitor with newly diagnosed OPD amenable to SABR will be randomised to either:

Arm A: SABR to all known sites of OPD with continuation of first line therapy ET and CDK 4/6 inhibitor Arm B: Physician's choice of systemic treatment

Patients must have evidence of radiological response to ET and CDK 4/6 inhibitor for a minimum of ...

Gender

ALL

Eligibility criteria

• • INCLUSION CRITERIA
• Patients will be eligible for inclusion in this trial if all the following criteria apply:
• • 1. Patient has signed the AVATAR-II Patient Information and Consent Form (PICF)
• • 2. Male or female, ≥ 18 years of age at the time signing consent
• • 3. Patients with histologically proven ER-positive, HER2-negative advanced breast cancer receiving an ET in combination with a CDK 4/6 inhibitor. Biopsy of metastatic disease if technically feasible but not mandatory
• • 4. Patients must have evidence of extracranial metastatic disease, with no evidence of uncontrolled intracranial metastases
• • 5. Patients must have evidence of radiological response to ET and CDK 4/6 inhibitor for a minimum of six months prior to randomisation (defined as either stable disease or partial response) Note: Patient must have ongoing stability/response in at least one lesion at the time of randomisation.
• 6. Evidence of new or existing OPD, as determined by the Investigator and defined according to RECIST1.1 (33), via CT on a per-lesion basis (between 1-5 metastases, including the primary) as follows:
• • At least a 20% increase in the diameter of a lesion, taking as reference the smallest diameter on a previous CT scan with an absolute increase of at least 5 mm
• • Appearance of a new lesion(s) Note: A new lesion can be identified using various imaging modalities, such as PET-CT or WBBS, as long as the lesion is visible on serial CT scans.
• • 7. For patients with liver or lung metastases, maximum of 3 oligoprogressive lesions in single organ
• • 8. All OPD must be amenable to SABR, as per the radiotherapy guidelines in section 11.1 and Appendix 4 and 5
• • 9. ECOG performance status 0-2
• • 10. Life expectancy ≥ 6 months
• • 11. Clinician and patient are willing to continue current line of therapy
• • 12. Patient is able to complete QoL questionnaires, and other assessments required as part of the study
• • EXCLUSION CRITERIA
• Patients will not be eligible for inclusion in this trial if any of the following criteria apply:
• • 1. Is pregnant or lactating at the time of randomisation
• • 2. Evidence of more than one clone of metastatic disease e.g., a patient with both ER-positive and triple negative clones of disease And ER-negative and/or HER2-positive disease would be excluded from the study
• • 3. Evidence of leptomeningeal disease
• • 4. Evidence of malignant cord compression
• • 5. Evidence of lesion within femoral bone requiring surgical fixation
• • 6. Patients with risk of bone fracture are not candidate for SABR (Appendix 4 and 5)
• • 7. Previous chemotherapy for metastatic disease Note: chemotherapy for primary breast cancer is allowed
• • 8. Contraindications to radiotherapy
• • 9. Any condition deeming the patient unsuitable to comply with the study
• • 10. Substantial overlap with previously treated area. Reirradiation is permitted with the condition that the combined plan adheres to the specific dose constraints outlined in this protocol. It is advised to use biological effective dose (BED) calculations to correlate previous doses with the tolerance doses documented below

Trial Officials