Abstract 142P
Background
Dual blockade of HER2 promises increased pathological complete response (pCR) rates compared with single blockade in the presence of chemotherapy for HER2-positive (+) primary breast cancer. We have reported that CpCRypN0 was confirmed in 46% (98/212); in 62% and 34% of ER-negative and ER-positive patients, respectively, from the neoadjuvant JBCRG-16 study (Breast Cancer 25:407-15, 2018). Long-term 5-year follow-up after surgery has been successful.
Methods
This was a randomised phase II, five-arm study (trial no: UMIN000007576) to evaluate the efficacy and safety of lapatinib and trastuzumab (6 weeks) followed by lapatinib and trastuzumab plus weekly paclitaxel (12 weeks) with/without prolonged anti-HER2 therapy prior to chemotherapy (18 vs. 6 weeks), and with/without endocrine therapy in HER2+ primary breast cancer patients. After surgery, patients received an anthracycline-based regimen according to the physician’s choice mainly depending on the efficacy of neoadjuvant treatment, followed by trastuzumab and endocrine therapy (in ER+). We evaluated the 5-year disease-free survival (DFS), distant-DFS (DDFS), and overall survival by the Kaplan-Meier method.
Results
The 5-year DFS was 87.8% (95%CI, 82.5-91.6); it was higher in patients with CpCRypN0 than in those without CpCRypN0 (91.7% vs 85.1%; p=0.0387). Among non-pCR patients, G2b (defined as only focal invasive tumor residues confirmed in the removed breast tissue; near pCR) was confirmed in 9 of 35 ER- patients and in 11 of 78 ER+ patients; no survival event was observed in the 20 patients with G2b. Adjuvant anthracycline therapy was performed in 48%; 5-year DDFS was similar between patients with and without adjuvant anthracycline. Four (T3N1 in 3) patients had brain metastasis; 2 of them had achieved CpCRypN0 and omitted adjuvant anthracycline.
Conclusions
A good prognosis was observed in patients who had CpCRypN0 after neoadjuvant treatment, including those with near pCR. The omission of adjuvant anthracycline may be considered for patients with CpCRypN0, however, the risk of brain metastasis should be taken into consideration.
Clinical trial identification
This trial is registered with UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number UMIN000007576.
Editorial acknowledgement
Legal entity responsible for the study
Japan Breast Cancer Research Group.
Funding
Japan Breast Cancer Research Group.
Disclosure
T. Fujisawa: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Novartis Pharma; Financial Interests, Personal, Speaker’s Bureau: Kyowa Kirin. N. Masuda: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Takeda Pharmaceutical; Financial Interests, Institutional, Funding: Chugai Pharmaceutical; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: Kyowa Kirin; Financial Interests, Institutional, Funding: Novartis Pharma; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Nippon Kayaku; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Personal, Member of the Board of Directors: Japanese Breast Cancer Society (JBCS); Non-Financial Interests, Personal, Member of the Board of Directors: Japan Breast Cancer Research Group (JBCRG) Association. N. Yamamoto: Financial Interests, Institutional, Principal Investigator: Chugai Pharmaceutical; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Japan Breast Cancer Research Group (JBCRG); Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Sanofi. H. Iwata: Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal and Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal and Institutional, Research Grant: Sanofi; Financial Interests, Personal, Principal Investigator: Novartis Pharma; Financial Interests, Personal, Advisory Board: Novartis Pharma; Financial Interests, Personal and Institutional, Research Grant: Novartis Pharma; Financial Interests, Personal, Advisory Board: Kyowa Kirin; Financial Interests, Personal, Principal Investigator: Kyowa Kirin; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Research Grant: Nippon Boehringer Ingelheim; Financial Interests, Personal and Institutional, Research Grant: Nippon Kayaku; Financial Interests, Personal and Institutional, Research Grant: Amgen. H. Bando: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Novartis Pharma . T. Aruga: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca. E. Tokunaga: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical. S. Ohtani: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer. T. Takano: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Celltrion Healthcare; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Eisai. K. Inoue: Financial Interests, Institutional, Principal Investigator: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Sanifi; Financial Interests, Institutional, Principal Investigator: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Personal, Invited Speaker: Eisai. M. Takada: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Pfizar; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Nippon Kayaku. K. Aogi: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Mochida Pharmaceutical; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical. K. Kuroi: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Kyowa Kirin . S. Ohno: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Eisai. S. Morita: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly Japan; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical .M. Toi: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Takeda Pharmaceutical; Financial Interests, Institutional, Research Grant: Takeda Pharmaceutical; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Personal, Advisory Board: Kyowa Kirin; Financial Interests, Institutional, Research Grant: Kyowa Kirin; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Non-Financial Interests, Personal, Member of the Board of Directors: Japan Breast Cancer Research Group (JBCRG) Association; Financial Interests, Institutional, Research Grant: Japan Breast Cancer Research Group (JBCRG) Association; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Exact Science; Financial Interests, Personal, Invited Speaker: Novartis Pharma; Financial Interests, Personal, Advisory Board: Konica Minolta; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Shimadzu; Financial Interests, Institutional, Research Grant: Shimadzu; Non-Financial Interests, Institutional, Member of the Board of Directors: KBCRN; Non-Financial Interests, Institutional, Member of the Board of Directors: OOTR; Financial Interests, Personal, Invited Speaker: Yakult; Financial Interests, Institutional, Research Grant: Yakult; Financial Interests, Personal, Invited Speaker: Nippon Kayaku; Financial Interests, Institutional, Research Grant: Nippon Kayaku; Financial Interests, Institutional, Research Grant: AFI technologies; Financial Interests, Personal, Advisory Board: Athenex Oncology; Financial Interests, Personal, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Terumo; Financial Interests, Personal, Advisory Board: Luxonus; Financial Interests, Institutional, Research Grant: Luxonus; Financial Interests, Institutional, Research Grant: Shionogi; Financial Interests, Institutional, Research Grant: GL Science; Financial Interests, Personal, Advisory Board: Kansai Medical Net. All other authors have declared no conflicts of interest.