1423 - High-dose chemotherapy (HDCT) with hematopoietic stem cell transplantation (HSCT) in high-risk breast cancer (BC) patients with _4 involved axillary lymph nodes (ALN): 20-year follow-up of a randomized phase 3 study

Background

Adjuvant HDCT for high-risk BC is not beneficial overall compared to conventional chemotherapy at the cost of considerable toxicity. HDCT benefit, however, may be present in very high-risk patients (i.e. >9 involved ALN) and in triple negative (TN) BC patients, although long-term results are lacking for most initial studies. We evaluated long-term outcome of a randomized phase 3 study, conducted from 1993 to 99.

Methods

Patients aged <56 years with early BC and ≥4 involved ALN were randomized to either conventional chemotherapy or HDCT as adjuvant systemic treatment. The conventional arm consisted of 5x fluorouracil, epirubicin and cyclophosphamide (FEC) 3-weekly. In the HDCT arm, the 5^th FEC was replaced by cyclophosphamide 6000 mg/m², thiotepa 480 mg/m², carboplatin 1600 mg/m² and supported with autologous HSCT (Rodenhuis, NEJM 2003). We collected 20-year follow-up data from medical records, general practitioners, and the Netherlands Cancer Registry. Endpoints were relapse free survival (RFS), overall survival (OS), BC specific survival (BCSS), and safety based on intention to treat analyses.

Results

885 patients (64% 4-9 ALN, 36% >9 ALN; 53% ER+/HER2-, 23% HER2+, 16% TN, 8% unknown) were randomized to FEC (n = 443) or HDCT (n = 442). The table shows efficacy results of univariable Cox models. With 20 years median follow-up, relapse or death occurred in 272 patients (61%) who received FEC vs in 257 (58%) HDCT patients (HR 0.88; 95% CI 0.74-1.05). The effect of HDCT compared to FEC was most pronounced in patients with >9 involved ALN and in TNBC patients. In 138 TNBC patients the 20-year OS estimate was 52% after HDCT vs 39% after FEC. Long-term safety and BCSS will also be presented at the meeting.Table: 187O

Conclusions

Long-term follow-up confirms survival benefit of HDCT in BC patients with >9 involved ALN and suggests benefit in TNBC patients.

Clinical trial identification

NCT03087409.

Legal entity responsible for the study

High-risk breast cancer study group from the Netherlands Working Party on Autologous Transplantation in Solid Tumors.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

T.G. Steenbruggen: Financial support: Memidis Pharma unrelated to the submitted work. V.C.G. Tjan-Heijnen: Research funding through grants institution: Eisai, Roche, Pfizer, Novartis, and AstraZeneca; Compensation for service as a consultant: AstraZeneca, Pfizer, Novartis, and Roche; Honoraria: Pfizer, Roche, and Novartis; Travel expenses: Pfizer, Novartis, and Roche. S.C. Linn: Institutional research funding: AstraZeneca, Amgen, BMS, Genentech, Roche, and Sanofi; Advisory board member: AstraZeneca, Novartis, Roche and Sanofi. E.G.E. de Vries: Consulting/advisory board fees: Synthon, Pfizer and Sanofi; Grants: Novartis, Amgen, Roche/Genentech, Regeneron, Chugai, Synthon, AstraZeneca, Radius Health, CytomX Therapeutics and Nordic Nanovector, all to the hospital and unrelated to the submitted work. G.S. Sonke: Institutional research funding: AstraZeneca, Merck, Novartis, Roche, unrelated to the submitted work. All other authors have declared no conflicts of interest.