Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer

Conditions

Breast Cancer

Keywords

Stage III, HER2 negative, homologous recombination deficiency (HRD)

Brief summary

Investigator-initiated, international, multicentre, randomized, open-label, (neo)adjuvant phase III study in target population (stage III, HER2-negative, BRCA1-like breast cancer patients) comparing optimized standard-dose chemotherapy with intensified, alkylating chemotherapy with stem cell rescue.

Seefat RL, Vliek SB, de Jong VMT, Balduzzi S, Mandjes IA, Retèl VP, Eekhout I, Delfos M, Schot M, Holtkamp MJ, van Rosmalen MM, Leeneman B, Blommestein H, Huitema ADR, Rosenberg EH, Nederlof PM, Chan TWS, van Rhenen A, Wondergem MJ, Schaap NPM, Snijders TJF, Van der Poel MWM, Plattel WJ, van Werkhoven E, van Tinteren H, Smidt ML, Wesseling J, Jonkers J, Rottenberg S, Vrancken Peeters MTFD, Voermans C, Maduro JH, Kroep JR, Schroder CP, Kuip EJM, Gonçalves A, Nuver J, Wymenga ANM, Bijlsma RM, van der Wall E, Konings IRHM, Tjan-Heijnen VCG, Jongen-Lavrencic M, Jager A, Linn SC.

2026-07-01

10.1016/s1470-2045(26)00131-2

High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: the randomized phase III NeoTN trial.

Vliek S, Hilbers FS, van Werkhoven E, Mandjes I, Kessels R, Kleiterp S, Lips EH, Mulder L, Kayembe MT, Loo CE, Russell NS, Vrancken Peeters MTFD, Holtkamp MJ, Schot M, Baars JW, Honkoop AH, Vulink AJE, Imholz ALT, Vrijaldenhoven S, van den Berkmortel FWPJ, Meerum Terwogt JM, Schrama JG, Kuijer P, Kroep JR, van der Padt-Pruijsten A, Wesseling J, Sonke GS, Gilhuijs KGA, Jager A, Nederlof P, Linn SC.

2023-09-095 citations

10.1038/s41523-023-00580-9

Abstract OT2-07-08: Substantially improving the cure rate of high-risk BRCA1-like breast cancer patients with personalized therapy (SUBITO) - an international randomized phase III trial

S.B. Vliek, Agnes Jager, M. Jonge-Lavrencic, JP Lotz, Anthony Gonçalvès et al. (19 authors)

Cancer Research2018-02-154 citations

10.1158/1538-7445.sabcs17-ot2-07-08

Interventions

DRUGddAC-CP-Olaparib

ddAC-CP-Olaparib

DRUGddAC-mini CTC

ddAC - mini CTC

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

No

Inclusion criteria

* Women and men with stage III adenocarcinoma of the breast harboring signs of a breast cancer with features of homologous recombination deficiency (HRD) * Age of 18-65 years * The tumor must be HER2-negative * Treatment must start within 8 weeks after the last surgical resection * Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Exclusion criteria

* Previous radiation therapy * Previous chemotherapy * Any previous treatment with a PARP-inhibitor, including olaparib * Pre-existing neuropathy from any cause in excess of Grade 1 * Chronic concomitant use of known strong or moderate CYP3A inducers

Design outcomes

Primary

Measure	Time frame	Description
Overall survival in all patients	assessed up to 120 months	time from randomization to death from any cause in all patients

Secondary

Measure	Time frame	Description
Overall survival in patients without a germline BRCA1/2 mutation	assessed up to 120 months	time from randomization to death from any cause in without a germline BRCA1/2 mutation
Recurrence free interval in all patients	assessed up to 120 months	time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first in all patients
Recurrence free interval in patients with an HR impaired tumor	assessed up to 120 months	time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first in patients with an HR impaired tumor
Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03	up to 30 days after end of treatment	Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03
cost-effectiveness measured by costs per quality-adjusted life years (QALYs)	assessed up to 120 months	cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
Patient reported outcomes	assessed up to 24 months	Patient reported outcomes; including quality of life (QoL) determined by a comprehensive panel of QoL questionnaires
cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)	assessed up to 120 months	cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)

Countries

France, Netherlands

Contacts

PRINCIPAL_INVESTIGATORSabine Linn, Prof. MD

NKI-AvL

Outcome results

None listed