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Listen "Christian Singer MD: Neoadjuvant Olaparib Combination Beats Standard of Care in Patients with Homologous Recombination Deficient BRCA 1/2-Positive Triple-Negative Breast Cancer"
Episode Synopsis
Audio Journal of Oncology, August 5th, 2025
An interview with:
Christian Singer MD,
Head, Center for Breast Health, Department of Obstetrics & Gynecology, Comprehensive Cancer Center, Medical University of Vienna.
CHICAGO, USA—Your patients whose triple-negative breast cancers test positive for BRCA 1/2 mutations, could do better if you gave them the poly ADP ribose polymerase (PARP) inhibitor olaparib together with carboplatin, as neoadjuvant therapy, rather than a standard docetaxel/epirubicin/cyclophosphamide combination.
That’s according to the prospective randomized phase two ABCSG 45 trial reported by Austrian researchers at the 2025 Annual Meeting of the American Society of Clinical Oncology held in Chicago. Peter Goodwin heard the details from first author Christian Singer of the University of Vienna:
Audio Journal of Oncology: Christian Singer, Medical University of Vienna.
ASCO 2025 ABSTRACT 510:
Title:
Prospective randomized phase II trial to assess the efficacy and safety of neo-adjuvant olaparib/carboplatin (OC) in comparison to docetaxel/epirubicin/cyclophosphamide (TAC) in patients with early triple-negative breast cancer (TNBC) with homologous recombination deficiency (HRD): Primary results from the ABCSG 45 trial.
Background:
Carboplatin-based regimen are effective in patients (pts) with eTNBC, and olaparib improves the outcome of pts with BRCA1/2 pathogenic variants (PV), but the safety / efficacy of OC co-treatment in HRD-positive TNBC is unknown. ABCSG 45 (EU CT 2024-512821-10) is a prospective multicenter phase II study investigating the efficacy and tolerability of OC compared to conventional chemotherapy in HRD-positive eTNBC.
Methods:
Pts with HRD (Myriad genetics)-positive eTNBC were randomized to 6 cycles of olaparib (100 mg bid, days 4-16) / carboplatin (AUC 5) q3w, or 6 cycles of docetaxel/epirubicin/cyclophosphamide (75/50/500) q3w (TAC). In an initial dose-finding phase, 100 mg bid was identified as olaparib combination dose. Stratification factors were tumoral BRCA1/2 and menopausal status. Primary endpoint was centrally assessed residual cancer burden (RCB), pCR and QoL were secondary endpoints. Planned sample size was 90 pts, randomized 1:1 to achieve 80% power (two-sided alpha=0.05) to detect a RCB 0/I difference of 31%. Differences between treatment arms were assessed with a two-sided Cochran Mantel-Haenszel test using stratification factors. Pre-defined subgroup analysis was performed with logistic regression.
Results:
A total of 90 pts (OC: n=46; TAC: n=44), of whom 42 (47%) were BRCA1/2 PV carriers, were randomized between November 2019 and December 2023. Median age was 50.5 years (range 27.0-80.0). 40% had cT1, 55.6% cT2, and 4.4% cT3/4 tumors, and 60% of pts were clinically N0. 94.4% of tumors were G3, and Ki67 was >60% in 71.1%. Overall, the RCB0/I rate with OC was 52.2% vs. 70.5% with TAC (stratified risk difference = -18.8% (95%CI: -39.6% to 2.0%); p=0.068). In pts with BRCA1/2 PV, RCB0/I rates were comparable: 77.3% (OC) vs. 65.0% (TAC), while in 47 pts with BRCA1/2 wild type (WT), OC was significantly less effective: RCB0/I of 29.2% vs 73.9% in TAC (interaction p=0.008). pCR was achieved in 47.8% (OC) vs 59.1% (TAC; p=0.231). In pts with a BRCA1/2 PV, OC resulted in 77.3% pCR rate, vs. TAC 65.0%, in BRCA1/2 WT pts pCR was achieved by 20.8% (OC) vs. 56.5% (TAC) (interaction p=0.021). OC treatment resulted in more ≥ grade 3 hematologic toxicities with 30% vs 3% thrombocytopenia and 43% vs 18% neutropenia but caused fewer non-hematological toxicities.
Conclusions:
In this prospective randomized study in HRD-positive TNBC, 6 cycles of TAC resulted in strikingly high RCB0/I and pCR rates, independent of BRCA1/2 status. 6 cycles of OC achieved a pCR rate of >77% in BRCA1/2 PV but were less effective in pts with BRCA1/2 WT disease. These results may help to optimize neoadjuvant treatment strategies in TNBC.
This research was conducted with support from AstraZeneca Austria GmbH
Authors:
Christian Singer, Dominik Hlauschek, Daniel Egle, Zsuzsanna Bago-Horvath, Georg Pfeiler, Christine Brunner, Christian Peters-Engl, Edgar Petru, Daniel Reimer, Renate Pusch, Michael Seifert, Petra Pichler, Christoph Suppan, Annette Reiner, Richard Greil, Yen Tan, Rupert Bartsch, Katharina Knoll, Anna Kermanidis, Michael Gnant
Organizations
Department of Obstetrics and Gynecology and Center for Breast Health, Comprehensive Cancer Center, Medical University of Vienna and Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria, Austrian Breast and Colorectal Cancer Study Group, Wien, Austria, Department of Gynecology, Breast Cancer Center Tirol, Medical University of Innsbruck and Austrian Breast and Colorectal Cancer Study Group, Innsbruck, Austria, Department of Pathology and Comprehensive Cancer Center, Medical University of Vienna, and Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria, Department of Gynecology, Breast Cancer Center Tirol, Medical University of Innsbruck, Innsbruck, Austria, Institute for Gynecological Oncology and Senology, Karl Landsteiner Society, Hietzing Hospital, Vienna, Austria, Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria, Ordensklinikum Linz, Barmherzige Schwestern, Abteilung Interne I, Medizinische Onkologie und Hämatologie, Linz, Austria, Clinical Department for Internal Medicine 1, University Hospital St Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria, Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria, Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria, IIIrd Medical Department, Paracelsus Medical University, Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials, Cancer Cluster Salzburg, and Austrian Breast and Colorectcal Cancer Study Group, Salzburg, Austria, Department of Obstetrics and Gynecology and Center for Breast Health, Comprehensive Cancer Center, Medical University of Vienna, Wien, Austria, Department of Medicine I, Division of Oncology, Medical University of Vienna and Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria, Austrian Breast and Colorectal Cancer Study Group, Viena, Austria, Comprehensive Cancer Center, Medical University of Vienna and Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria
https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.510
An interview with:
Christian Singer MD,
Head, Center for Breast Health, Department of Obstetrics & Gynecology, Comprehensive Cancer Center, Medical University of Vienna.
CHICAGO, USA—Your patients whose triple-negative breast cancers test positive for BRCA 1/2 mutations, could do better if you gave them the poly ADP ribose polymerase (PARP) inhibitor olaparib together with carboplatin, as neoadjuvant therapy, rather than a standard docetaxel/epirubicin/cyclophosphamide combination.
That’s according to the prospective randomized phase two ABCSG 45 trial reported by Austrian researchers at the 2025 Annual Meeting of the American Society of Clinical Oncology held in Chicago. Peter Goodwin heard the details from first author Christian Singer of the University of Vienna:
Audio Journal of Oncology: Christian Singer, Medical University of Vienna.
ASCO 2025 ABSTRACT 510:
Title:
Prospective randomized phase II trial to assess the efficacy and safety of neo-adjuvant olaparib/carboplatin (OC) in comparison to docetaxel/epirubicin/cyclophosphamide (TAC) in patients with early triple-negative breast cancer (TNBC) with homologous recombination deficiency (HRD): Primary results from the ABCSG 45 trial.
Background:
Carboplatin-based regimen are effective in patients (pts) with eTNBC, and olaparib improves the outcome of pts with BRCA1/2 pathogenic variants (PV), but the safety / efficacy of OC co-treatment in HRD-positive TNBC is unknown. ABCSG 45 (EU CT 2024-512821-10) is a prospective multicenter phase II study investigating the efficacy and tolerability of OC compared to conventional chemotherapy in HRD-positive eTNBC.
Methods:
Pts with HRD (Myriad genetics)-positive eTNBC were randomized to 6 cycles of olaparib (100 mg bid, days 4-16) / carboplatin (AUC 5) q3w, or 6 cycles of docetaxel/epirubicin/cyclophosphamide (75/50/500) q3w (TAC). In an initial dose-finding phase, 100 mg bid was identified as olaparib combination dose. Stratification factors were tumoral BRCA1/2 and menopausal status. Primary endpoint was centrally assessed residual cancer burden (RCB), pCR and QoL were secondary endpoints. Planned sample size was 90 pts, randomized 1:1 to achieve 80% power (two-sided alpha=0.05) to detect a RCB 0/I difference of 31%. Differences between treatment arms were assessed with a two-sided Cochran Mantel-Haenszel test using stratification factors. Pre-defined subgroup analysis was performed with logistic regression.
Results:
A total of 90 pts (OC: n=46; TAC: n=44), of whom 42 (47%) were BRCA1/2 PV carriers, were randomized between November 2019 and December 2023. Median age was 50.5 years (range 27.0-80.0). 40% had cT1, 55.6% cT2, and 4.4% cT3/4 tumors, and 60% of pts were clinically N0. 94.4% of tumors were G3, and Ki67 was >60% in 71.1%. Overall, the RCB0/I rate with OC was 52.2% vs. 70.5% with TAC (stratified risk difference = -18.8% (95%CI: -39.6% to 2.0%); p=0.068). In pts with BRCA1/2 PV, RCB0/I rates were comparable: 77.3% (OC) vs. 65.0% (TAC), while in 47 pts with BRCA1/2 wild type (WT), OC was significantly less effective: RCB0/I of 29.2% vs 73.9% in TAC (interaction p=0.008). pCR was achieved in 47.8% (OC) vs 59.1% (TAC; p=0.231). In pts with a BRCA1/2 PV, OC resulted in 77.3% pCR rate, vs. TAC 65.0%, in BRCA1/2 WT pts pCR was achieved by 20.8% (OC) vs. 56.5% (TAC) (interaction p=0.021). OC treatment resulted in more ≥ grade 3 hematologic toxicities with 30% vs 3% thrombocytopenia and 43% vs 18% neutropenia but caused fewer non-hematological toxicities.
Conclusions:
In this prospective randomized study in HRD-positive TNBC, 6 cycles of TAC resulted in strikingly high RCB0/I and pCR rates, independent of BRCA1/2 status. 6 cycles of OC achieved a pCR rate of >77% in BRCA1/2 PV but were less effective in pts with BRCA1/2 WT disease. These results may help to optimize neoadjuvant treatment strategies in TNBC.
This research was conducted with support from AstraZeneca Austria GmbH
Authors:
Christian Singer, Dominik Hlauschek, Daniel Egle, Zsuzsanna Bago-Horvath, Georg Pfeiler, Christine Brunner, Christian Peters-Engl, Edgar Petru, Daniel Reimer, Renate Pusch, Michael Seifert, Petra Pichler, Christoph Suppan, Annette Reiner, Richard Greil, Yen Tan, Rupert Bartsch, Katharina Knoll, Anna Kermanidis, Michael Gnant
Organizations
Department of Obstetrics and Gynecology and Center for Breast Health, Comprehensive Cancer Center, Medical University of Vienna and Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria, Austrian Breast and Colorectal Cancer Study Group, Wien, Austria, Department of Gynecology, Breast Cancer Center Tirol, Medical University of Innsbruck and Austrian Breast and Colorectal Cancer Study Group, Innsbruck, Austria, Department of Pathology and Comprehensive Cancer Center, Medical University of Vienna, and Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria, Department of Gynecology, Breast Cancer Center Tirol, Medical University of Innsbruck, Innsbruck, Austria, Institute for Gynecological Oncology and Senology, Karl Landsteiner Society, Hietzing Hospital, Vienna, Austria, Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria, Ordensklinikum Linz, Barmherzige Schwestern, Abteilung Interne I, Medizinische Onkologie und Hämatologie, Linz, Austria, Clinical Department for Internal Medicine 1, University Hospital St Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria, Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria, Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria, IIIrd Medical Department, Paracelsus Medical University, Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials, Cancer Cluster Salzburg, and Austrian Breast and Colorectcal Cancer Study Group, Salzburg, Austria, Department of Obstetrics and Gynecology and Center for Breast Health, Comprehensive Cancer Center, Medical University of Vienna, Wien, Austria, Department of Medicine I, Division of Oncology, Medical University of Vienna and Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria, Austrian Breast and Colorectal Cancer Study Group, Viena, Austria, Comprehensive Cancer Center, Medical University of Vienna and Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria
https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.510
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