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Found 2 Presentations For Request "Abs: 176P"

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176P - Germline mutation status and therapy response in patients with homologous recombination deficient, HER2-negative early breast cancer: Results of the GeparOLA study (NCT02789332)

Presentation Number
176P
Speakers
  • Jan Hauke (Köln, Germany)
Date
17.09.2020

Abstract

Background

The phase II GeparOla study randomized patients (pts) with homologous recombination deficient (HRD), HER2-negative early breast cancer (BC) to receive neoadjuvant treatment with paclitaxel 80 mg/m2 iv weekly plus olaparib tablets 100 mg (PO) twice daily for 12 weeks or paclitaxel plus carboplatin AUC 2 iv (PCb) weekly for 12 weeks (PCb) prior to epirubicin/cyclophosphamide (EC). We determined pathological complete response (pCR, ypT0/is ypN0) according to treatment arm and germline mutation status.

Methods

HRD was determined centrally for all pts using the myChoice® HRD test (Myriad). Of the 106 pts included in the mITT set, 105 were analyzed for germline mutations in BRCA1/2 and 16 other cancer predisposition genes. 76/105 patients had hormone receptor negative (HR-) and 29/105 pts hormone receptor positive (HR+) tumours.

Results

68 pts received PO and 37 PCb. The pCR rates were 53.3% overall (56/105), 55.9% in the PO arm (38/68) and 48.6% in the PCb arm (18/37). We identified pathogenic BRCA1/2 mutations in 59 of the 105 pts; nine of the 46 BRCA1/2-negative pts carried mutations in additional genes analyzed. Overall, pCR rates were higher in pts with BRCA1/2 mutations than in pts without (62.7% vs. 41.3%; P=0.047). In the PO arm, pCR rates were 61.0% (25/41) for pts with BRCA1/2 mutations compared to 48.1% (13/27) for pts without (P=0.428). In the PCb arm, pCR rates were 66.7% (12/18) and 31.6% (6/19), respectively (P=0.071). Differences in pCR rates between PO and PCb arm were not significant for pts with BRCA1/2 mutations (61.0% vs. 66.7% P=0.901) or pts without mutation (48.1% vs. 31.6%, P=0.412). Regardless of the treatment arm, pCR rates were higher in HR- than in HR+ pts (57.9%, 44/76 vs. 41.4%, 12/29;). We observed highest pCR rates in HR- pts with BRCA1/2 mutations (65.8%, 25/38) and lowest in HR+ pts without BRCA1/2 mutations (0%, 0/8).

Conclusions

Even in pts with HRD tumours, germline BRCA1/2 mutation status predicts therapy outcome. For pts without BRCA1/2 mutations, higher pCR rates were observed in the PO arm vs. the PCb arm. Results should be interpreted with caution due to limited sample size but may guide future clinical trials.

Clinical trial identification

NCT02789332.

Legal entity responsible for the study

GBG Forschungs GmbH.

Funding

AstraZeneca; Köln Fortune Program, Faculty of Medicine, University of Cologne, Germany.

Disclosure

P.A. Fasching: Honoraria (self), Lectures: Amgen; Honoraria (self), Advisory/Consultancy, Advisory Board: Roche; Research grant/Funding (self), Research grant/Funding (institution), Research Support: BionTech; Honoraria (self), Advisory/Consultancy, Advisory Board: Pfizer; Honoraria (self), Advisory/Consultancy, Advisory Board: Celgene; Honoraria (self), Lectures: Daiichi-Sankyo; Honoraria (self), Advisory/Consultancy, Advisory Board, Lectures: Merck Sharp&Dohme; Honoraria (self), Advisory/Consultancy, Advisory Board: Macrogenics; Honoraria (self), Advisory/Consultancy, Advisory Board: Eisai; Research grant/Funding (institution), Research Support: Cepheid; Honoraria (institution), Advisory/Consultancy, Advisory Board, Lectures: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Research Support, Advisory Board: Novartis; Honoraria (self), Advisory/Consultancy, Advisory Board: AstraZeneca. C. Jackisch: Honoraria (self): AstraZeneca; Honoraria (self): Roche. K.E. Rhiem: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Pfizer. J. Huober: Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): Lilly; Honoraria (self): Celgene; Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): MSD; Honoraria (self): AbbVie; Honoraria (self): Eisai; Research grant/Funding (institution): Hexal; Research grant/Funding (institution): Celgene; Honoraria (self), Research grant/Funding (institution): Novartis; Travel/Accommodation/Expenses: Daiichi. S. Seiler: Research grant/Funding (institution), GeparOla study was supported by AstraZeneca: AstraZeneca; Honoraria (self), Advisory/Consultancy, Advisory Boards: Amgen; Honoraria (self), Advisory/Consultancy, Advisory Boards: Hexal; Honoraria (self), Presentations: Roche; Honoraria (self), Advisory/Consultancy, Advisory Boards: Mundipharma; Travel/Accommodation/Expenses: Novartis. A. Schneeweiss: Research grant/Funding (institution): Celgene; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Molecular Partner; Honoraria (self), Speaker Bureau/Expert testimony, Medical writing grant: Roche; Honoraria (self), Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly. C. Denkert: Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Daiichi Sankyo; Research grant/Funding (self): Myriad Genetics; Shareholder/Stockholder/Stock options, Cofounder and shareholder: Sividon Diagnostics/Myriad. M. Untch: Honoraria (institution): AbbVie; Honoraria (institution): Amgen; Honoraria (institution): AstraZeneca; Honoraria (institution): BMS; Honoraria (institution): Celgene GmbH; Honoraria (institution): Daiji Sankyo; Honoraria (institution): Eisai GmbH; Honoraria (institution): Lilly Deutschland; Honoraria (institution): Lilly int.; Honoraria (institution): MSD Merck; Honoraria (institution): Mundipharma; Honoraria (institution): Myriad Genetics; Honoraria (self): Odonte; Honoraria (institution): Pfizer GmbH; Honoraria (self): PUMA Biotechnology; Honoraria (institution): Roche Pharma AG; Honoraria (institution): Sanofi Aventis Deutschland GmbH; Honoraria (institution): TEVA Pharmaceuticals Ind Ltd; Honoraria (institution): Novartis; Honoraria (institution): Pierre Fabre; Honoraria (institution): Clovis Oncology. J-U. Blohmer: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): SonoScape. R.K. Schmutzler: Research grant/Funding (institution): Cologne Fortune Program. S. Loibl: Honoraria (institution), Research grant/Funding (institution): AbbVie; Honoraria (institution), Research grant/Funding (institution): Amgen; Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): Celgene; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution), Research grant/Funding (institution): Roche; Honoraria (institution): Seattle Genetics; Honoraria (self): Chugai; Research grant/Funding (self): Teva; Research grant/Funding (self): Vifor; Honoraria (institution): PriME/Medscape; Honoraria (institution), Research grant/Funding (institution): Daiichi Sankyo; Honoraria (institution): Lilly; Honoraria (institution): Samsung; Advisory/Consultancy, paid to institution: Eirgenix; Honoraria (institution): BMS; Honoraria (institution): Puma; Honoraria (institution): MSD; Research grant/Funding (institution): Immunomedics. All other authors have declared no conflicts of interest.

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Poster Display session

1165P - Subgroup analysis by Ki-67 and primary tumour origins of the randomized, placebo-controlled phase III study of surufatinib in advanced well-differentiated extrapancreatic neuroendocrine tumours (SANET-ep)

Presentation Number
1165P
Speakers
  • Zhiwei Zhou (Guangzhou, China)
Date
17.09.2020

Abstract

Background

Surufatinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (1,2,3), fibroblast growth factor receptor 1 and colony stimulating factor 1 receptor, has demonstrated superior efficacy in extrapancreatic neuroendocrine tumors (NETs) in a phase III study (SANET-ep, ESMO 2019 Abs. LBA76). The proliferation marker Ki-67 and primary tumor origins are the major prognostic factors in NETs.

Methods

The post-hoc efficacy analysis of surufatinib versus placebo was conducted by Ki-67 subcategory (<3%, 3-10%, >10%) and primary tumor origins (foregut, midgut, hindgut, others or unknown) in patients (pts) with advanced well-differentiated (grade 1 or 2) extrapancreatic NETs. The primary endpoint (progression-free survival [PFS]) and secondary endpoint (objective response rate [ORR]) both by investigator assessment (RECIST1.1) were analyzed.

Results

Median PFS was significantly prolonged with surufatinib compared to placebo in subgroups of Ki-67 3-10% (7.6 vs 4.6 months [mo], hazard ratio [HR] 0.47, P=0.0012), Ki-67 >10% (8.3 vs 2.1 mo, HR 0.14, P<0.0001), foregut (8.4 vs 4.6 mo, HR 0.29, P=0.0001) and hindgut (8.3 vs 2.1 mo, HR 0.35, P=0.0014). There was numerical PFS improvement with surufatinib compared to placebo in the rest subgroups: Ki 67 <3% (13.9 vs 7.4 mo, HR 0.43, P=0.0557), midgut (19.2 vs 8.9 mo, HR not analyzed due to small sample size) and unknown origin (9.2 vs 5.5 mo, HR 0.56, P=0.2943). ORR in the subgroups of Ki-67 <3%, 3-10%, >10% with surufatinib were 4.8%, 7.7%% and 20.0% respectively. There was no objective response in the placebo arm. ORR in the subgroups of foregut, midgut and unknown origin with surufatinib was 18.4%, 16.7% and 10.0% respectively while no response was observed in subgroups of hindgut or other origins.

Conclusions

Surufatinib demonstrated clinically significant benefits for pts with advanced well-differentiated extrapancreatic NETs compared to placebo. Results of this exploratory analysis were consistent with those reported for the SANET-ep primary analysis, and improved outcomes were observed across major subgroups.

Clinical trial identification

NCT02588170.

Legal entity responsible for the study

Hutchison MediPharma Limited.

Funding

Hutchison MediPharma Limited.

Disclosure

J. Li, J. He: Full/Part-time employment: Hutchison MediPharma Limited. W. Su: Shareholder/Stockholder/Stock options, Full/Part-time employment: Hutchison MediPharma Limited. All other authors have declared no conflicts of interest.

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