Abstract OT2-30-01: Nordictrip, a translational randomized phase-3study exploring the effect of the addition of capecitabine to carboplatinum-based chemotherapy in early “triple negative” breast cancer, ClinicalTrials.gov Identifier: NCT04335669
Authors: Loman Niklas , Linderholm Barbro , Ahlgren Johan , Kimbung Siker , Zander Lina , Magnusson Heidi Grill , Kjellman Eva-Christin , Raaberg Ann Julia , Jensen Maj-Britt Raaby , Borg Åke , Staaf Johan , Ståhlberg Anders , Bendahl Pär-Ola , Laenkholm Anne-Vibeke , Tanner Minna , Bjarnadóttir Olöf , Johannsson Oskar , Ejlertsen Bent , Lindman Henrik 
Published: March 2022

Background: A striking heterogeneity combined with an absence of highly efficient targeted treatments necessitates a continued effort to optimize the choice of chemotherapy for patients with triple negative breast cancer (TNBC). Neoadjuvant therapy has become the standard of care for high risk TNBC in order to potentially reduce breast and axillary surgery, start medical treatment early, allow genomic screening and guide post neoadjuvant therapy. Much attention is drawn to the use of immunotherapy in early TNBC, but there is also interesting data suggesting a potential to optimize the use of conventional chemotherapy. According to one meta-analysis including data from nine randomized controlled trials, the addition of platinum salts in the preoperative setting increases the pathologic complete response (pCR) rate in TNBC (Poggio 2018). A second meta-analysis, evaluating the effect of capecitabine in early breast cancer indicates an additional benefit from adding capecitabine to conventional chemotherapy in terms of an increased recurrence-free survival in the subset of TNBC (Mackelenbergh SABCS 2019). An adjuvant trial in TNBC suggests that the beneficial effect of capecitabine may be confined to patients with a non-basal like phenotype of TNBC (Lluch 2020), a subset that correlates with the homologous repair non-deficient subset which constitutes 41 % of TNBC in a mainly south Swedish population based cohort (Staaf 2019). The effect of capecitabine in platinum treated early TNBC is unknown. Objectives: We are conducting a multi-center randomized controlled trial evaluating the effect on the pCR rate by the addition of capecitabine to optimal platinum based and dose dense preoperative chemotherapy in early TNBC. Method: 820 patients (pts) with early TNBC stage 1 (≥20 mm) - 3 will be randomized 1:1 between two treatment arms A and B. A: Epirubicine Cyclophosphamide (EC) q2w x 4 followed by Carboplatin AUC 5 q3w with weekly paclitaxel x 12. B: Epirubicine Cyclophosphamide with capecitabine daily for two weeks (CEX) q3w x 4 followed by Carboplatin AUC 5 q3w with weekly paclitaxel x 12 The primary endpoint is pCR rate in the different treatment strata, and the primary translational endpoint will be the potential difference of treatment effect stratified for HRD-status in the primary tumor. Secondary endpoints include IDFS in subsets of TNBC, eg according to gene-expression-based subtypes of TNBC (Lehmann 2011, Burstein 2015), and germline mutation status of hereditary breast cancer genes. Tumor material for genotypig is collected at baseline, at surgery and optionally after two treatment cycles. Sequential blood samples are collected for tsDNA analysis during and after treatment termination. Results: The trial, which is a collaborative effort between the national breast cancer groups in the participating countries, has been postponed by the pandemic but is now recruiting according to plan. So far 56 patients out of 820 have been recruited at 15 sites in Sweden and Denmark. Additional Sites in Sweden, Denmark, Iceland and Finland are preparing to join the study. For update please see: www.NordicTrip.se; E-mail address: Nordictrip.onkologi@skane.se

Citation Format: Niklas Loman, Barbro Linderholm, Johan Ahlgren, Siker Kimbung, Lina Zander, Heidi Grill Magnusson, Eva-Christin Kjellman, Ann Julia Raaberg, Maj-Britt Raaby Jensen, Åke Borg, Johan Staaf, Anders Ståhlberg, Pär-Ola Bendahl, Anne-Vibeke Laenkholm, Minna Tanner, Olöf Bjarnadóttir, Oskar Johannsson, Bent Ejlertsen, Henrik Lindman. Nordictrip, a translational randomized phase-3study exploring the effect of the addition of capecitabine to carboplatinum-based chemotherapy in early “triple negative” breast cancer, ClinicalTrials.gov Identifier: NCT04335669 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-30-01.