Abstract OT2-02-01: Comparison of axillary sentinel lymph node biopsy versus no axillary surgery in patients with early-stage invasive breast cancer and breast-conserving surgery: A randomized prospective surgical trial. The intergroup-sentinel-mamma (INSEMA)-trial
Authors: Reimer T , von Minckwitz G , Loibl S , Hildebrandt G , Denkert C , Nekljudova V , Kundt G , Becker D , Gerber B 
Published: May 2016

Background:

Currently, axillary surgery for breast cancer is considered as staging procedure that does not seem to influence breast cancer mortality, since the risk of developing metastasis depends mainly on the biological behaviour of the primary. Based on this, the postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement.

Trial design:

The goal of INSEMA is to show that early-stage breast cancer patients with reduced extent of axillary surgery are not inferior regarding invasive disease-free survival (IDFS) outcome. Patients with planned breast-conserving surgery (BCS) will be first randomized (1:4 ratio) to either no axillary surgery or axillary sentinel lymph node biopsy (SLNB). Patients with SLNB and pN+(sn) status will be secondly randomized (1:1 ratio) to either SLNB alone or completion axillary lymph node dissection (ALND) in cases with less than three involved nodes (one or two macrometastases).

Primary objective:

-IDFS after BCS (non-inferiority question)

Inclusion criteria:

-Written informed consent

-Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy)

-Age at least 35 years

-Preoperative imaging techniques with estimated tumor size of maximal 5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status)

-Clinically and sonographically tumor-free axilla prior to core biopsy

-In cases with cN0 and iN+, a negative core biopsy or fine needle aspiration biopsy of the suspected lymph node is required

-No clinical evidence for distant metastasis (M0)

-Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation)

Statistics:

Assumptions for first randomization:

-The 5-year IDFS for women with cN0/iN0 axillary lymph nodes and T1/T2 disease is considered to be 88%

-Clinical non-inferiority is defined as the non-SLNB group having a 5-year IDFS of not less than 85% and if the hazard ratio (HR) is less than 1.271 when compared with the SLNB group

The total number of patients in the per-protocol set of the first randomization must be increased from 3,796 to 5,940 (936 events) due to unequal-sample-size design.

Assumptions for second randomization:

-The 5-year IDFS for women with pN+(sn) axillary lymph nodes (1-2 macrometastases) and T1/T2 disease is considered to be 81%

-Clinical non-inferiority is defined as the SLNB alone group having a 5-year IDFS of not less than 76.5% and if the hazard ratio (HR) is less than 1.271 when compared with the completion ALND group

The total number of patients to be included into the per-protocol set for the second randomization will be approximately 1,968. Finally, the calculated total case number for per-protocol analyses is 6,740 (5,940 German and 800 Austrian patients), the expected total number of randomized patients is 7,095.

Time lines:

-First patient in: September 2015

-Last patient in: August 2019

-Final analysis: End of 2024

Funding by Deutsche Krebshilfe (grant no. 110580).

Citation Format: Reimer T, von Minckwitz G, Loibl S, Hildebrandt G, Denkert C, Nekljudova V, Kundt G, Becker D, Gerber B. Comparison of axillary sentinel lymph node biopsy versus no axillary surgery in patients with early-stage invasive breast cancer and breast-conserving surgery: A randomized prospective surgical trial. The intergroup-sentinel-mamma (INSEMA)-trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-02-01.