Clinical trial NCT06704945: No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy
Official title: No Axillary Surgical Treatment in Clinically Lymph Node Negative Patients on Ultrasonography After Neoadjuvant Chemotherapy: a Prospective, Phase III Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Neoadjuvant Therapy
Sentinel Lymph Node Biopsy
Keywords: Omission of axillary surgery after neoadjuvant chemotherapy
Breast cancer
Neoadjuvant chemotherapy
De-escalation
Omission of surgery
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Asan Medical Center
First posted: 2024-11-26
Enrollment: 464
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: NEO-NAUTILUS is a prospective, multicenter, randomized phase III clinical trial to evaluate whether omitting axillary lymph node surgery (ALND or SLNB) in clinically lymph node-negative breast cancer patients after neoadjuvant chemotherapy is non-inferior to performing SLNB in terms of 5-year disease-free survival.

Detailed description: Background:

* No prospective studies have proven that axillary lymph node surgery improves survival in breast cancer patients.
* The ACOSOG Z0011 trial showed that additional axillary dissection did not improve recurrence or survival, even with a 23.7% incidence of non-sentinel node metastases.
* NSABP B-32 established the oncologic safety of SLNB, significantly reducing complications like lymphedema compared to axillary dissection. However, SLNB still carries risks of lymphedema, sensory changes, seromas, and infections.
* The trend has now shifted toward identifying candidates for omitting axillary surgery to minimize unnecessary complications.
* The SOUND trial demonstrated non-inferiority of omitting SLNB in early-stage breast cancer patients with negative axillary ultrasound. Five-year distant metastasis-free survival was comparable between SLNB and no-SLNB groups (97.7% vs. 98.0%).
* Improved ultrasound accuracy (e.g., FNR: 13.7% in SOUND; 11.3% in NAUTILUS) and the therapeutic contribution of whole-breast radiation likely support these findings.
* Patients with a complete pathological response (pCR) in the breast post-NAC rarely have residual lymph node metastases, reducing the need for axillary surgery.
* Single-arm studies (e.g., EUBREAST-01, ASICS, ASLAN) have explored omitting axillary surgery in patients with confirmed breast pCR. However, these studies face limitations due to small sample sizes, single-arm design, and the necessity of axillary surgery if pCR is not achieved.
* To address these limitations, the NEO-NAUTILUS trial proposes the first randomized trial to compare disease-free survival and local recurrence rates between patients who omit SLNB (experimental group) and those who undergo SLNB (control group) after NAC, focusing on patients deemed axillary node-negative by ultrasound.

Eligibility criteria: Inclusion Criteria:

* Women aged ≥19 years.
* Histologically confirmed invasive breast carcinoma treated with neoadjuvant chemotherapy.
* Clinical staging prior to NAC: cT1-3, cN0, M0 (AJCC 8th Edition).
* If pre-NAC staging is cT1-3, cN1, M0, must meet the following criteria:

  1. HER2-positive or triple-negative breast cancer (TNBC).
  2. At least 30% reduction in tumor size on MRI after NAC (comparing pre- and post-NAC MRI).
* Negative axillary lymph node status on ultrasound after NAC.
* Planned for breast-conserving surgery with completed neoadjuvant chemotherapy (at least half the planned regimen must be completed).
* ECOG performance status of 0-2.
* Signed written informed consent before enrollment.

Exclusion Criteria:

* History of any cancer within the past 5 years.
* Bilateral breast cancer.
* Patients requiring mastectomy.
* Tumor size \>5 cm after NAC.
* Male breast cancer.
* Pregnant or breastfeeding women.
* Inability to understand and complete questionnaires.

Primary outcomes:
measure: Invasive Disease Free Survival (iDFS)
timeFrame: 5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 5 years
measure: Distant Metastasis Free Survival (DMFS)
timeFrame: 5 years
measure: Axillary recurrence rate
timeFrame: 5 years
measure: Locoregional Recurrence Rate (LRR)
timeFrame: 5 years
measure: QoL
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
References:
citation: Jung JG, Ahn SH, Lee S, Kim EK, Ryu JM, Park S, Lim W, Jung YS, Chung IY, Jeong J, Chang JH, Shin KH, Chang JM, Moon WK, Han W. No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial. BMC Cancer. 2022 Feb 20;22(1):189. doi: 10.1186/s12885-022-09273-1.