Universität zu Köln

Blohmer, Jens-Uwe, Link, Theresa, Reinisch, Mattea, Just, Marianne, Untch, Michael, Stotzer, Oliver, Fasching, Peter A., Schneeweiss, Andreas, Wimberger, Pauline, Seiler, Sabine, Huober, Jens, Thill, Marc, Jackisch, Christian, Rhiem, Kerstin, Solbach, Christine, Hanusch, Claus, Seither, Fenja, Denkert, Carsten, Engels, Knut, Nekljudova, Valentina and Loibl, Sibylle (2022). Effect of Denosumab Added to 2 Different nab-Paclitaxel Regimens as Neoadjuvant Therapy in Patients With Primary Breast Cancer The GeparX 2 x 2 Randomized Clinical Trial. JAMA Oncol., 8 (7). S. 1010 - 1019. CHICAGO: AMER MEDICAL ASSOC. ISSN 2374-2445

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Abstract

IMPORTANCE Adjuvant denosumab might improve disease-free survival in hormone receptor (HR)-positive primary breast cancer (BC). The optimal neoadjuvant nab-paclitaxel schedule in terms of efficacy and safety is unclear. OBJECTIVE To determine whether adding denosumab to anthracycline/taxane-containing neoadjuvant chemotherapy (NACT) increases the pathological complete response (pCR) rate and which nab-paclitaxel schedule is more effective in the NACT setting. DESIGN, SETTING, AND PARTICIPANTS The GeparX was a multicenter, prospective, open-label, phase 2b, 2 x 2 randomized clinical trial conducted by GBG and AGO-B at 38 German sites between February 2017 and March 2019. The analysis data set was locked September 4, 2020; analysis was completed November 13, 2020, Patients had unilateral or bilateral primary BC, stage cT2-cT4a-d or cT1c, with either clinically node-positive or pathologically node-positive or HR-negative disease, or Ki-67 proliferation index greater than 20%, or ERBB2 (formerly HER2)-positive BC. INTERVENTIONS Patients were randomized to receive or not receive denosumab, 120 mg subcutaneously every 4 weeks for 6 cycles, and either nab-paclitaxel, 125 mg/m(2) weekly for 12 weeks or days 1 and 8 every 3 weeks for 4 cycles (8 doses), followed by 4 cycles of epirubicin/cyclophosphamide, 90/600 mg/m(2) (every 2 weeks or every 3 weeks). Carboplatin was given in triple-negative BC (TNBC), and trastuzumab biosimilar ABP980 plus pertuzumab was given in ERBB2-positive BC (ERBB2-positive substudy). MAIN OUTCOMES AND MEASURES The primary outcome was pCR rates between arms for each randomization. RESULTS A total of 780 female (n = 779) and male (n = 1) patients (median [range] age, 49.0 [22-80] years) were randomized to the 4 treatment groups. The pCR (ypT0 ypN0) rate was 41.0% (90% CI, 37%-45%) with denosumab vs 42.8% (90% CI, 39%-47%) (P = .58) without denosumab, irrespective of BC subtype. Nab-paclitaxel weekly resulted in a significantly (significance level of alpha = .10) higher pCR rate of 44.9% (90% CI, 41%-49%) vs 39.0% (90% CI, 35%-43%) (P = .06) with nab-paclitaxel days 1 and 8 every 3 weeks. The pCR rates for nab-paclitaxel schedules in subgroups were only significantly different for TNBC (60.4% vs 50.0%; P = .06). Grade 3 to 4 toxic effects did not differ with or without denosumab. Nonhematologic toxic effects of grade 3 to 4 were higher with nab-paclitaxel weekly (33.7% vs 24.1%; P = .004). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, denosumab added to anthracycline/taxane-based NACT did not improve pCR rates. Nab-paclitaxel at a dosage of 125 mg/m(2) weekly significantly increased the pCR rate compared with the days land 8, every-3-weeks schedule overall and in TNBC, but generated higher toxicity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Blohmer, Jens-Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Link, Theresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinisch, Mattea UNSPECIFIED UNSPECIFIED UNSPECIFIED Just, Marianne UNSPECIFIED UNSPECIFIED UNSPECIFIED Untch, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Stotzer, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Fasching, Peter A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneeweiss, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Wimberger, Pauline UNSPECIFIED UNSPECIFIED UNSPECIFIED Seiler, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Huober, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Thill, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Jackisch, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Rhiem, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Solbach, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Hanusch, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Seither, Fenja UNSPECIFIED UNSPECIFIED UNSPECIFIED Denkert, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Engels, Knut UNSPECIFIED UNSPECIFIED UNSPECIFIED Nekljudova, Valentina UNSPECIFIED UNSPECIFIED UNSPECIFIED Loibl, Sibylle UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-696177
DOI:	10.1001/jamaoncol.2022.1059
Journal or Publication Title:	JAMA Oncol.
Volume:	8
Number:	7
Page Range:	S. 1010 - 1019
Date:	2022
Publisher:	AMER MEDICAL ASSOC
Place of Publication:	CHICAGO
ISSN:	2374-2445
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ZOLEDRONIC ACID; ADJUVANT DENOSUMAB; CHEMOTHERAPY; BISPHOSPHONATES; WOMEN; MULTICENTER; METASTASIS; PREVENTION; LETROZOLE Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69617