Abstract 1846
Background
CLEOPATRA study demonstrated the efficacy and safety of pertuzumab (P) + trastuzumab (T) + docetaxel (D) but efficacy results of Japanese subgroup weren’t consistent with the whole study results. A phase IV, multicenter, prospective, COMACHI study was conducted in Japan to re-confirm the efficacy and safety of P+T+D demonstrated in the CLEOPATRA study.
Methods
Patients (pts) with HER2-positive breast cancer who were diagnosed as Stage IV or recurred more than a year after (neo)adjuvant taxane chemotherapy completion were enrolled. Pts were administered study drugs intravenously every 3 weeks. Discontinuation of D was allowed after cycle 6. After discontinuation of D, pts were given maintenance by T+P, however not allowed to receive hormonal therapy for HR positive pts. We defined PFS as the primary endpoint. To demonstrate a median PFS of 12.4 months (mos) or more, which was observed in the placebo arm in the CLEOPATRA study.
Results
From November 2013 to September 2015, 132 pts were enrolled and all pts were treated with T+P at least once. The median age was 56.5 years old and 102 pts (77.3%) had not received prior HER2 therapy. Median cycles of T and P were both 24.0 (range 2.0-71.0) and that of D was 6.0 (range 0.0-65.0). Pts characteristics and subgroup analysis results are shown in the Table below.Table:
353P
Name | Level | Patients | Events | Time to event |
---|---|---|---|---|
[n (%)] | [n (%)] | [Median (95% CI)] | ||
All | n/a | 132 (100.0%) | 66 (50.0%) | 22.8 (16.9, 34.8) |
Prior (neo) adjuvant therapy(Excluding hormone therapy) | YES | 38 ( 28.8%) | 18 (47.4%) | 27.7 (12.4, NE ) |
NO | 94 ( 71.2%) | 48 (51.1%) | 20.8 (16.9, 38.8) | |
Age | < 65 | 96 ( 72.7%) | 49 (51.0%) | 22.8 (16.5, NE ) |
>- 65 | 36 ( 27.3%) | 17 (47.2%) | 33.1 (18.7, NE ) | |
Disease Type at Screening | VISCERAL DISEASE | 81 ( 61.4%) | 49 (60.5%) | 18.4 (13.8, 33.7) |
NON-VISCERAL DISEASE | 51 ( 38.6%) | 17 (33.3%) | NE (20.7, NE ) | |
ER/PgR Status | POSITIVE | 72 ( 54.5%) | 39 (54.2%) | 18.9 (14.7, 33.1) |
NEGATIVE | 60 ( 45.5%) | 27 (45.0%) | 33.7 (20.6, NE ) | |
HER2 Status IHC/ISH | IHC < = 2+ and ISH POSITIVE | 21 ( 15.9%) | 13 (61.9%) | 16.5 (10.4, 34.8) |
IHC 3+ | 111 ( 84.1%) | 53 (47.7%) | 22.9 (18.9, NE ) | |
Stage | < STAGE IV | 61 ( 46.2%) | 24 (39.3%) | 28.4 (22.8, NE ) |
STAGE IV | 71 ( 53.8%) | 42 (59.2%) | 18.9 (14.3, 33.7) |
Median PFS was 22.8 mos [95% CI, 16.9-34.8], and thereby a median PFS of 12.4 mos or more was confirmed. The incidence of typical Grade 3/4 adverse events were febrile neutropenia (31.1%), neutropenia (24.2%), leukopenia (10.6%), and diarrhea (4.5%), and these findings are consistent with the CLEOPATRA study except for febrile neutropenia. Febrile neutropenia lead to only one case of treatment discontinuation and it was manageable.
Conclusions
The efficacy and safety of P+T+D in Japanese pts were consistent with those of the CLEOPATRA study and we confirmed this treatment as a standard care at 1st line therapy for HER2-positive metastatic breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Chugai Pharmaceutical Co., Ltd.
Funding
Chugai Pharmaceutical Co., Ltd.
Disclosure
N. Masuda: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Kyowa-Kirin; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Daiichi Sankyo; Officer / Board of Directors: Japan Breast Cancer Research Group Association. S. Ohtani: Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: AstraZeneca. S. Nagai: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli-Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd. Y. Komoike: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eli-Lilly; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony, the publisher, for writing atricle: Nikkei Business Publications, Inc. Y. Ito: Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Speaker Bureau / Expert testimony, Research grant / Funding (self): Taiho; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli-Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self): Eisai; Research grant / Funding (institution): Covance; Research grant / Funding (institution): IQVIA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): A2healthcare; Research grant / Funding (institution): Parexel; Research grant / Funding (institution): Kyowa-Kirin. M. Ikeda: Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: Asahi Kasei Pharma Corporation; Speaker Bureau / Expert testimony: Kyowa-Kirin; Speaker Bureau / Expert testimony: Ono; Speaker Bureau / Expert testimony: Mundipharma; Speaker Bureau / Expert testimony: Taiho; Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Nippon Kayaku; Research grant / Funding (institution): Hisamitsu; Officer / Board of Directors, engaged in the project of medical practice guidline: Japanese Breast cancer society; Officer / Board of Directors, the leader of clinical trial comittee: Setouchi Breast Project Comprehensive Support Organization. K. Ishida: Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Nippon Kayaku. T. Nakayama: Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Eli-Lilly; Speaker Bureau / Expert testimony: Novartis. T. Takashima: Speaker Bureau / Expert testimony, Officer / Board of Directors: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony, Officer / Board of Directors: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony: Kyowa-Kirin; Speaker Bureau / Expert testimony: Eli-Lilly. T. Asakawa: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. S. Matsumoto: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. D. Shimizu: Full / Part-time employment: Chugai Pharmaceutical Co., Ltd. M. Takahashi: Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eisai; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Eli-Lilly; Speaker Bureau / Expert testimony: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Kyowa-Kirin; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Daiichi Sankyo; Speaker Bureau / Expert testimony: Allergan; Speaker Bureau / Expert testimony, Research grant / Funding (institution): FUJIFILM Toyama Chemical; Speaker Bureau / Expert testimony: Nihon Medi-Physics; Honoraria (self), for wrtitin article: The Asahi Shimbun Company. All other authors have declared no conflicts of interest.
Resources from the same session
5887 - Factors of importance in procuring tumoroids from colorectal liver metastasis biopsies for precision medicine.
Presenter: Lars Henrik Jensen
Session: Poster Display session 2
Resources:
Abstract
2196 - FUSAFE individual patient data meta-analysis (MA) to assess the performance of dihydropyrimidine dehydrogenase (DPD) gene polymorphisms for predicting grade 4-5 fluoropyrimidine (FP) toxicity
Presenter: Marie-Christine Etienne-Grimaldi
Session: Poster Display session 2
Resources:
Abstract
2859 - Treatments (tx) after progression to first-line FOLFOXIRI + bevacizumab (bev) in metastatic colorectal cancer (mCRC) patients (pts): A pooled analysis of TRIBE and TRIBE-2 studies by GONO.
Presenter: Daniele Rossini
Session: Poster Display session 2
Resources:
Abstract
3888 - Randomized phase III study of sequential treatment with capecitabine or 5-fluorouracil (FP) plus bevacizumab (BEV) followed by the addition with oxaliplatin (OX) versus initial combination with OX+FP+ BEV in the first-line chemotherapy for metastatic colorectal cancer: The C-cubed study
Presenter: Takeshi Nagasaka
Session: Poster Display session 2
Resources:
Abstract
1065 - Early tumour shrinkage (ETS), depth of response (DpR) and associated survival outcomes in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC) classified according to Köhne prognostic category: retrospective analysis of the panitumumab (Pmab) PRIME study
Presenter: Andrea Sartore-Bianchi
Session: Poster Display session 2
Resources:
Abstract
1702 - Randomized phase II trial of CAPOX with planned oxaliplatin stop-and-go strategy as adjuvant chemotherapy after curative resection of colon cancer (CCOG-1302 study)
Presenter: Hiroyuki Yokoyama
Session: Poster Display session 2
Resources:
Abstract
5104 - A metabolomic recurrence score for risk-stratification of elderly patients (pts) with early colorectal cancer (eCRC)
Presenter: Samantha Di Donato
Session: Poster Display session 2
Resources:
Abstract
5285 - RAS mutant allele fraction in plasma predicts benefit to anti-angiogenic based first line treatment in metastatic colorectal cancer
Presenter: Giulia Martini
Session: Poster Display session 2
Resources:
Abstract
1790 - Impact of prophylactic systemic antibiotics (SA) on outcome of patients (pts) with RAS-wildtype (RAS-wt) metastatic colorectal carcinoma (mCRC) treated with cetuximab-based first-line therapy. Subgroup analysis of the german non-interventional study ERBITAG
Presenter: Stephan Sahm
Session: Poster Display session 2
Resources:
Abstract
3059 - Intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): A randomized, multicenter, prospective, phase III trial
Presenter: Rongxin Zhang
Session: Poster Display session 2
Resources:
Abstract