Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial

Toralf Reimer; Angrit Stachs; Kristina Veselinovic; Thorsten Kühn; Jörg Heil; Silke Polata; Frederik Marmé; Thomas Müller; Guido Hildebrandt; David Krug; Beyhan Ataseven; Roland Reitsamer; Sylvia Ruth; Carsten Denkert; Inga Bekes; Dirk-Michael Zahm; Marc Thill; Michael Golatta; Johannes Holtschmidt; Michael Knauer; Valentina Nekljudova; Sibylle Loibl; Bernd Gerber

doi:10.1056/NEJMoa2412063

Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial

N Engl J Med. 2024 Dec 12. doi: 10.1056/NEJMoa2412063. Online ahead of print.

Authors

Toralf Reimer¹, Angrit Stachs¹, Kristina Veselinovic¹, Thorsten Kühn¹, Jörg Heil¹, Silke Polata¹, Frederik Marmé¹, Thomas Müller¹, Guido Hildebrandt¹, David Krug¹, Beyhan Ataseven¹, Roland Reitsamer¹, Sylvia Ruth¹, Carsten Denkert¹, Inga Bekes¹, Dirk-Michael Zahm¹, Marc Thill¹, Michael Golatta¹, Johannes Holtschmidt¹, Michael Knauer¹, Valentina Nekljudova¹, Sibylle Loibl¹, Bernd Gerber¹

Affiliation

¹ From the Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany (T.R., A.S., B.G.); University Hospital Ulm, Ulm, Germany (K.V., I.B.); Hospital Esslingen, Esslingen, Germany (T.K.); University Hospital Heidelberg, Heidelberg, Germany (J. Heil, M.G.); the Breast Unit, Sankt Elisabeth Hospital, Heidelberg, Germany (J. Heil, M.G.); Evang. Waldkrankenhaus Spandau, Berlin (S.P.); the Faculty of Medicine Mannheim, Department of Obstetrics and Gynecology, University of Heidelberg, Mannheim, Germany (F.M.); the Department of Obstetrics and Gynecology, Hanau City Hospital, Hanau, Germany (T.M.); the Department of Radiation Oncology, University Hospital Rostock, Rostock, Germany (G.H.); the Department of Radiotherapy and Radiation Oncology, University Hospital Hamburg-Eppendorf (UKE), Hamburg, Germany (D.K.); the Department of Radiation Oncology, University Medical Center Schleswig-Holstein, Kiel, Germany (D.K.); Medical School and University Medical Center OWL, Department of Gynecology and Obstetrics, Bielefeld University, Klinikum Lippe, Detmold, Germany (B.A.); Salzburg Regional Hospital, Salzburg, Austria (R.R.); Johanniter-Hospital Genthin-Stendal, Genthin, Germany (S.R.); the Institute of Pathology, Philipps-University Marburg and University Hospital Marburg (UKGM), Marburg, Germany (C.D.); Breast Center St. Gallen, Kantonsspital, St. Gallen, Switzerland (I.B.); SRH Wald-Klinikum Gera, Gera, Germany (D.-M.Z.); the Department of Gynecology and Gynecologic Oncology, Agaplesion Markus Hospital, Frankfurt am Main, Germany (M.T.); the German Breast Group, Neu-Isenburg, Germany (J. Holtschmidt, V.N., S.L.); and the Tumor and Breast Center Eastern Switzerland, St. Gallen, Switzerland (M.K.).

PMID: 39665649
DOI: 10.1056/NEJMoa2412063

Abstract

Background: Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear.

Methods: In this prospective, randomized, noninferiority trial, we investigated the omission of axillary surgery as compared with sentinel-lymph-node biopsy in patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size, ≤5 cm) who were scheduled to undergo breast-conserving surgery. We report here the per-protocol analysis of invasive disease-free survival (the primary efficacy outcome). To show the noninferiority of the omission of axillary surgery, the 5-year invasive disease-free survival rate had to be at least 85%, and the upper limit of the confidence interval for the hazard ratio for invasive disease or death had to be below 1.271.

Results: A total of 5502 eligible patients (90% with clinical T1 cancer and 79% with pathological T1 cancer) underwent randomization in a 1:4 ratio. The per-protocol population included 4858 patients; 962 were assigned to undergo treatment without axillary surgery (the surgery-omission group), and 3896 to undergo sentinel-lymph-node biopsy (the surgery group). The median follow-up was 73.6 months. The estimated 5-year invasive disease-free survival rate was 91.9% (95% confidence interval [CI], 89.9 to 93.5) among patients in the surgery-omission group and 91.7% (95% CI, 90.8 to 92.6) among patients in the surgery group, with a hazard ratio of 0.91 (95% CI, 0.73 to 1.14), which was below the prespecified noninferiority margin. The analysis of the first primary-outcome events (occurrence or recurrence of invasive disease or death from any cause), which occurred in a total of 525 patients (10.8%), showed apparent differences between the surgery-omission group and the surgery group in the incidence of axillary recurrence (1.0% vs. 0.3%) and death (1.4% vs. 2.4%). The safety analysis indicates that patients in the surgery-omission group had a lower incidence of lymphedema, greater arm mobility, and less pain with movement of the arm or shoulder than patients who underwent sentinel-lymph-node biopsy.

Conclusions: In this trial involving patients with clinically node-negative, T1 or T2 invasive breast cancer (90% with clinical T1 cancer and 79% with pathological T1 cancer), omission of surgical axillary staging was noninferior to sentinel-lymph-node biopsy after a median follow-up of 6 years. (Funded by the German Cancer Aid; INSEMA ClinicalTrials.gov number, NCT02466737.).

Associated data

ClinicalTrials.gov/NCT02466737

Abstract

Associated data

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