Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany

Hanna Huebner, Christian M Kurbacher, Geoffrey Kuesters, Andreas D Hartkopf, Michael P Lux, Jens Huober, Bernhard Volz, Florin-Andrei Taran, Friedrich Overkamp, Hans Tesch, Lothar Häberle, Diana Lüftner, Markus Wallwiener, Volkmar Müller, Matthias W Beckmann, Erik Belleville, Matthias Ruebner, Michael Untch, Peter A Fasching, Wolfgang Janni, Tanja N Fehm, Hans-Christian Kolberg, Diethelm Wallwiener, Sara Y Brucker, Andreas Schneeweiss, Johannes Ettl, Hanna Huebner, Christian M Kurbacher, Geoffrey Kuesters, Andreas D Hartkopf, Michael P Lux, Jens Huober, Bernhard Volz, Florin-Andrei Taran, Friedrich Overkamp, Hans Tesch, Lothar Häberle, Diana Lüftner, Markus Wallwiener, Volkmar Müller, Matthias W Beckmann, Erik Belleville, Matthias Ruebner, Michael Untch, Peter A Fasching, Wolfgang Janni, Tanja N Fehm, Hans-Christian Kolberg, Diethelm Wallwiener, Sara Y Brucker, Andreas Schneeweiss, Johannes Ettl

Abstract

Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry.

Methods: Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor-positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria.

Results: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive.

Conclusion: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials.

Trial registration: Clinicaltrials, NCT02338167 , Registered 14 January 2015 - retrospectively registered.

Keywords: Advanced breast cancer; Antihormone therapy; Heregulin; MM-121; Metastatic; Seribantumab.

Conflict of interest statement

E.B. has received honoraria from Novartis, Celgene, Riemser, Pfizer, Hexal, Amgen, onkowissen.de for consulting, clinical research management or medical education activities. M.W.B.’s institution has received research funding from Novartis and BioNTech. J.E. has received honoraria from Roche, Celgene, Novartis, Pfizer, Pierre Fabre, Teva, and travel support from Celgene, Pfizer, Teva, and Pierre Fabre. T.N.F. has received honoraria from AstraZeneca, Celgene, Eisai, Pfizer, and Roche. P.A.F. reports grants from Novartis, Cepheid, and BioNTech, personal fees from Novartis, Roche, Pfizer, Celgene, Daiichi-Sankyo, Teva, AstraZeneca, Merck Sharp & Dohme, Pierre-Fabre, Macrogenics, Eisai, and Puma. A.D.H. has received honoraria from Teva, Genomic Health, Celgene, AstraZeneca, Novartis, Pfizer, Lilly, MSD, Eisai and Roche. J.H. has received honoraria from Novartis, Roche, Celgene, Teva, and Pfizer and travel support from Roche, Celgene, and Pfizer. W.J. has received honoraria and research grants from Novartis. C.M.K. has received honoraria from Amgen, Eli Lilly, Novartis, Mundipharma, Pfizer, PharmaMar, Riemser, Roche and Tesaro and had consulting or advisory role for Amgen, Axios, Eli Lilly, Hilotherm, Mundipharma, NewCo, Novartis, Pfizer, Riemser, Roche and Tesaro. He received research funding from Astra Zeneca, Axios, MSD Sharp & Dohme, NewCo, Novartis, Pfizer, PharmaMar, Riemser, Seattle Genetics and travel or accommodation expenses from Amgen, Hexal, Pfizer, PharmaMar, Tesaro, TEVA Oncology. H.-C.K. has received honoraria from Carl Zeiss meditec, Teva, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, Janssen-Cilag, GSK, LIV Pharma, Roche, MSD, SurgVision, Onkowissen and Genomic Health. D.L. has received honoraria from Amgen, AstraZeneca, Celgene, Lilly, Loreal, MSD, Novartis, Pfizer, Tesaro, and Teva. M.P.L. has received honoraria from Lilly, Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, Eisai, medac, and Genomic Health for advisory boards, lectures and travel support. V.M. has received speaker honoraria from Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, Pfizer, Pierre Fabre, Novartis, Roche, Teva, and Janssen-Cilag and consultancy honoraria from Genomic Health, Roche, Pierre Fabre, Amgen, Daiichi-Sankyo, and Eisai. F.O. has received speaker and consultancy honoraria from Amgen, Celgene, AstraZeneca, Novartis, Roche, and MSD. A.S. has received honoraria from Roche, Celgene, AstraZeneca, Novartis, Pfizer, Zuckschwerdt Verlag GmbH, Georg Thieme Verlag, Aurikamed GmbH, MCI Deutschland GmbH, bsh medical communications GmbH, and promedicis GmbH. H.T. has received honoraria from Novartis, Roche, Celgene, Teva, and Pfizer and travel support from Roche, Celgene, and Pfizer. M.W. has received speaker honoraria from AstraZeneca, Celgene, and Novartis. G.K. was an employee at Merrimack Pharmaceuticals. All of the remaining authors (H.H., B.V., F.A.T., L.H., M.R., M.U., D.W., S.Y.B. have declared that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Patient selection
Fig. 2
Fig. 2
Progression-free survival relative to SHERBOC eligibility status. Kaplan–Meier curves for progression-free survival (PFS–1TL) in the therapy line before possible SHERBOC inclusion, relative to SHERBOC eligibility status
Fig. 3
Fig. 3
Overall survival relative to SHERBOC eligibility status. Kaplan–Meier curves for overall survival (OS–1TL) in the therapy line before possible SHERBOC inclusion, relative to SHERBOC eligibility status

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