31 oktober 2022: Bron: Annals of Oncology VOLUME 33, ISSUE 11P1149-1158, NOVEMBER 01, 2022

Wanneer borstkankerpatiënten met operabele triple negatieve borstkanker vooraf aan de operatie naast chemo het anti-PD medicijn durvalumab ernaast krijgen dan blijkt op drie jaars meting de overall overleving en ziekteprogressievrije overleving statistisch significant beter dan zonder durvalumab. Het primaire doel van de GeparNuevo studie was een complete remissie (pCR). Secundaire eindpunten waren invasieve ziektevrije overleving (iDFS), ziektevrije overleving op afstand (DDFS) en totale overleving (OS). 

Hoogtepunten van de studie:

  • •Aanzienlijke verbetering van secundaire eindpunten iDFS, DDFS en OS door toevoeging van durvalumab aan neoadjuvante chemotherapie.
  • •Verbetering van de overleving, hoewel er na de operatie geen aanvullende therapie met checkpointremmers - anti-PD medicijnen meer werd gegeven.
  • •Effect op lange termijn wordt gezien bij zowel patiënten die een complete remissie bewerkstelligden als bij patiënten die geen complete remissie bewerkstelligden.
  • •Het verbeterde overlevingsresultaat met therapie met checkpointremmers - anti-PD medicijnen wordt slechts gedeeltelijk verklaard door het verhoogde pCR-percentage.
  • •Onze resultaten suggereren dat er aanvullende antitumoreffecten op de lange termijn aanwezig zijn.

Hier de vertaling van de resultaten uit het abstract:


  • Tussen juni 2016 en oktober 2017 werden in totaal 174 patiënten gerandomiseerd. Na een mediane follow-up van 43,7 maanden hadden zich 34 voorvallen voorgedaan.
  • Ondanks een niet-significante toename van het pCR-percentage werden wel statistisch significante verschillen waargenomen voor 3-jaars iDFS, DDFS en OS:
  • iDFS was 85,6% met durvalumab versus 77,2% met placebo [hazard ratio (HR) 0,48, 95% betrouwbaarheidsinterval (BI ) 0,24-0,97, gestratificeerde log-rank P = 0,036];
  • DDFS 91,7% versus 78,4% (HR 0,31, 95% BI 0,13-0,74, P = 0,005);
  • OS 95,2% versus 83,5% (HR 0,24, 95% BI 0,08-0,72, P = 0,006).
  • pCR-patiënten hadden een 3-jaars iDFS van 95,5% met durvalumab en 86,1% zonder (HR 0,22, 95% BI 0,05-1,06).
  • In het niet-pCR-cohort was de 3-jaars iDFS 76,3% versus 69,7% (HR 0,67, 95% BI 0,29-1,54).
  • Multivariabele analyse bevestigde een durvalumab-effect onafhankelijk van het pCR-effect. Er zijn geen nieuwe veiligheidssignalen opgetreden.
Het volledige studierapport is gratis in te zien of te downloaden. Klik daarvoor op de titel van het abstract:


Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response


  • Significant improvement of secondary endpoints iDFS, DDFS and OS by adding durvalumab to neoadjuvant chemotherapy.
  • Survival improvement although no adjuvant checkpoint inhibitor therapy was given.
  • Long-term effect is seen in pCR as well as non-pCR patients.
  • The improved survival outcome with checkpoint inhibitor therapy is only partially explained by the increased pCR rate.
  • Our results suggest that additional long-term antitumour effects are present.


Addition of immune checkpoint inhibitors to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pathological complete response (pCR) rate by an absolute 9% (P = 0.287).

Patients and methods

Patients with cT1b-cT4a-d triple-negative breast cancer (TNBC) received durvalumab 1.5 g or placebo every 4 weeks added to nab-paclitaxel 125 mg/m2 weekly for 12 weeks, followed by durvalumab/placebo every 4 weeks plus epirubicin/cyclophosphamide every 2 weeks followed by surgery. Durvalumab was not continued after surgery. The primary objective was pCR. Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS).


A total of 174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab versus 77.2% with placebo [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.97, stratified log-rank P = 0.036]; DDFS 91.7% versus 78.4% (HR 0.31, 95% CI 0.13-0.74, P = 0.005); OS 95.2% versus 83.5% (HR 0.24, 95% CI 0.08-0.72, P = 0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In the non-pCR cohort 3-year iDFS was 76.3% versus 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed a durvalumab effect independent of the pCR effect. No new safety signals occurred.


Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of checkpoint inhibitors in the treatment of early TNBC.


The authors would like to thank all patients and their families participating in the trial, the central pathology team at the Charité University Hospital in Berlin as well as the team at the GBG Headquarters, especially Konstantin Reißmüller for managing the study, Christiane Prätor as the responsible data manager and Dr. Valentina Vladimirova for editorial assistance.


This work was supported by AstraZeneca (no grant number) and Celgene (BMS company) (no grant number).

Role of funding sources

The funders had no role in the collection, analysis or interpretation of the data, and had no access to the study data. The study statisticians (JR, VN) had access to the raw data. The report was reviewed by all authors. The sponsor (GBG Forschungs GmbH) has developed the study design and written the study protocol in collaboration with the members of the neoadjuvant sub-board of the German Breast Group (GBG) and AGO-B. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication.


MU reports personal fees and non-financial support from AbbVie, Amgen GmbH, AstraZeneca, Celgene GmbH, Daiji Sankyo, Eisai GmbH, Lilly Int., Merck Sharp & Dohme (MSD), Merck, Mundipharma, Myriad Genetics, Pfizer GmbH, Roche, Sanofi Aventis Deutschland GmbH, Teva, Novartis, Clovis Oncology; personal fees from Bristol Myers Squibb (BMS), Lilly Deutschland, Pierre Fabre, Seattle Genetics, Seagen, outside the submitted work. AS reports grants from Celgene, Roche, AbbVie; personal fees from Roche, AstraZeneca, Celgene, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly, Pfizer; other from Roche, outside the submitted work. CD reports grants from European Commission H2020, German Cancer Aid Translational Oncology, German Breast Group, during the conduct of the study; personal fees from Novartis, Roche, MSD Oncology, Daiichi Sankyo, AstraZeneca, Molecular Health, Merck, grants from Myriad; other from Sividon Diagnostics, outside the submitted work; has a patent VMScope digital pathology software with royalties paid, a patent WO2020109570A1-cancer immunotherapy pending, and a patent WO2015114146A1 and WO2010076322A1-therapy response issued. SL reports grants and other from AbbVie, non-financial support and other from Amgen, grants and other from AstraZeneca, other from Bayer, other from BMS, grants and other from Celgene, personal fees from Chugai, grants, non-financial support and other from Daiichi Sankyo, other from EirGenix, other from GSK, grants, non-financial support and other from Immunomedics/Gilead, other from Lilly, other from Merck, grants, non-financial support and other from Novartis, grants, non-financial support and other from Pfizer, other from Pierre Fabre, other from Prime/Medscape, non-financial support and other from Puma, grants, non-financial support and other from Roche, other from Samsung, non-financial support and other from Seagen, outside the submitted work; has a patent EP14153692.0 pending, a patent EP21152186.9 pending, a patent EP15702464.7 issued, a patent EP19808852.8 pending and a patent Digital Ki67 Evaluator with royalties paid. PAF reports personal fees from Novartis, grants from BioNTech, personal fees from Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, MSD, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia; grants from Cepheid, during the conduct of the study. JH reports personal fees and other from Pfizer, grants and personal fees from Novartis, Lilly; personal fees and other from Roche, personal fees from AbbVie, AstraZeneca, MSD, Eisai, Seagen, Gilead; grants and personal fees from Hexal; other from Daiichi, outside the submitted work. KR reports personal fees from AstraZeneca, MSD, Pfizer, outside the submitted work. TL reports personal fees and non-financial support from Roche, personal fees from Novartis, personal fees and non-financial support from Pfizer, personal fees from Tesaro, personal fees and non-financial support from MSD, personal fees from Amgen, personal fees from Clovis, non-financial support from Clegene, personal fees from Lilly, Myriad, GSK, Esai, outside the submitted work. JUB reports personal fees from Amgen, AstraZeneca, MSD, Novartis, Lilly, Pfizer, Exact Sciences, Molecular Health, Seagen, outside the submitted work. CH reports personal fees for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from AstraZeneca, Roche, Novartis, Lilly and Pfizer. PS reports personal fees, non-financial support and other from AbbVie, Janssen-Cilag, Amgen, Novartis, Pfizer, Gilead; grants, personal fees, non-financial support and other from Celgene; grants from AstraZeneca, outside the submitted work. All other authors have declared no conflicts of interest.

Data sharing

Will individual participant data be available (including data dictionaries)? Yes
What data in particular will be shared? Individual participant data that underlie the results reported in this article, after final analysis and publication of all secondary efficacy endpoints
What other documents will be available? Study protocol; statistical report (if necessary for the project)
When will data be available (start and end dates)? Beginning after final analysis and publication of all secondary efficacy endpoints; no end date
With whom? Researchers who provide translational research proposals. Proposals should be approved by the GBG scientific board.
For what types of analyses? To achieve aims in the approved proposal
By what mechanism will data be made available? Proposals should be directed to http://www.gbg.de/de/forschung/translationale-forschung.php; to gain access, data requestors will need to sign a data transfer agreement

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  • Figure thumbnail gr1
    Figure 1Kaplan–Meier estimates of (A) invasive disease-free survival (iDFS), (B) distant disease-free survival (DDFS) and (C) overall survival (OS) by treatment arm.
  • Figure thumbnail gr2ab
    Figure 2Kaplan–Meier estimates of (A) invasive disease-free survival (iDFS), (B) distant disease-free survival (DDFS) and (C) overall survival (OS) by pCR and treatment arm. The event-free rates at 36 months in each group are displayed above and below the curves.
  • Figure thumbnail gr2c
    Figure 2Kaplan–Meier estimates of (A) invasive disease-free survival (iDFS), (B) distant disease-free survival (DDFS) and (C) overall survival (OS) by pCR and treatment arm. The event-free rates at 36 months in each group are displayed above and below the curves.
  • Figure thumbnail gr3
    Figure 3Subgroup analysis of (A) invasive disease-free survival (iDFS) (univariate Cox regression model) and (B) pCR (univariate logistic regression model).


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