Phase 3 Trial of Carboplatin in Triple Negative Breast Cancer (TNBC) Patients with Residual Invasive Carcinoma After Neoadjuvant Chemotherapy (JONIE4:J-CAT Trial) Tanino H, Suzuki M, Kaise H, Miyashita M, Chishima T, Hayashi M, Miyoshi Y, Futamura M, Ohtani S, Nagahashi M, Ohta T, Kosaka Y, Ishikawa T, Hasegawa Y, Kubota T, Sangai T, Iwatani T, Yamada A, Akazawa K, Kohno N. Kobe University, Kobe, Hyogo, Japan; National Hospital Organization Chiba Medical Center, Chiba City, Chiba, Japan; Tokyo Medical University Ibaraki Medical Center, Inashikigun, Ibaraki, Japan; Kohnan Hospital, Kobe, Hyogo, Japan; Yokohama Rosai Hospital, Yokohama, Kanagawa, Japan; Dokkyo Medical University, Mibu, Tochigi, Japan; Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; Gifu University, Gifu, Japan; Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan; Niigata University, Niigata, Japan; St. Marianna University School of Medicine, Kawasaki, Knagawa, Japan; Kitasato University, Sagamihara, Kanagawa, Japan; Tokyo Medical University, Shinjuku-ku, Tokyo, Japan; Hirosaki Municipal Hospital, Hirosaki, Aomori, Japan; Kobe Kaisei Hospital, Kobe, Hyogo, Japan; Chiba University Graduate School of Medicine, Chiba, Chiba, Japan; Chigasaki Municipal Hospital, Chigasaki, Kanagawa, Japan; Kamiiida Daiichi General Hospital, Nagoya City, Aichi, Japan.

Background: Trial design: Eligibility criteria:

This is an open label, randomized phase III study that will enroll TNBC with residual invasive 1) ER and PgR<1%, HER2 0, 1+ or 2+ with FISH negative on core needle biopsy before the It is well known that the prognosis of non pCR TNBC patients was poor after anthracycline chemotherapy and surgical specimens. and taxan treatment. For such patients, capecitabine seems to be effective to reduce cancer after surgery with preoperative chemotherapy including both anthracycrine and taxan. 2) Preoperative chemotherapy including both anthracycrine and taxan. recurrence based on the HR 0.58 of the CREATE X trial (Masuda, N. et al. Adjuvant Patients are randomly assigned to either the carboplatin group or observation group. The Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 376, 2147. patients in the carboplatin group are treated with carboplatin at AUC 6 and those in the 3) Residual invasive cancer on breast tumors or lymph node metastasis in surgical specimens. observation group are observed at only 3 years. 2017) . However, the target of capecitabine is still unclear for TNBC. We classified non pCR 4) 20-79 year old women. tumors as BRCAness and Sporadic using BRCAness test (MRC-Holland, Amsterdam, the Observation 5) No chemotherapy within 5 years. Netherlands). The recurrence rate of the BRCAness group was about 80%. Carboplatine is Pathology NAC Surgery expected to be effective against BRCAness tumors, as it is a DNA damaging agent. In this Non-pCR R 6) Not bilateral breast cancer, without metastasis, no prior breast cancer. Carboplatin study BRCAness can be checked just before carboplatin treatment using surgical AUC 6 x4 7) No severe bone marrow suppression. specimens. Then the efficacy of carboplatin will be directly known to make comparison Specific aims: between DFS in the carboplatin group and that of the observation group. Primary objective is DFS (Disease Free Survival). STATISTICAL METHODS: Secondary objectives are overall survival and safety.

The 3 years recurrence rate of the observation group was estimated as 40% and hazard ratio at The prognosis of non pCR TNBC patients was poor after anthracycline and taxan treatment. P6-09-06 BRCAness as a prognostic marker in 0.58 based on the CREATE X trial. For both groups, 135 patients are necessary. This study is triple-negative breast cancer patients treated with powered to approximately 80% to test the superiority of carboplatin group at a 2-sided α=0.05 neoadjuvant chemotherapy: a multicenter retrospective using a stratified log-rank test. Study. Y Kosaka, H.Tanino et al 2018 SABCS (Sat. 8th Dec.)

Recurrence Free Survival Overall Survival (%) (%) 100 100 non-BRCAness (n=30)

80 non-BRCAness (n=30) 80 Activation Date: 22nd March 2018. 60 60 Contact information for people with a specific interest in the trial: 40 40 BRCAness (n=19) H. Tanino MD, PhD, Department of Breast Surgery, Kobe University, 7-5-2 Kusunoki-cho, Chuo- 20 20 BRCAness (n=19) ku, Kobe, Hyogo, 650-0017 Japan p < 0.01 p < 0.05 0 20 40 60 80 0 20 40 60 80 Cortazar P et al Lancet 2014 Time (months) Time (months)