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
5124 - STAR_PAC: Phase I clinical trial repurposing all trans retinoic acid (ATRA) as stromal targeting agent in a novel drug combination for pancreatic cancer.
Presenter: Hemant Kocher
Session: Poster Display session 2
Resources:
Abstract
5257 - Outcomes of First Line FOLFIRINOX (FFX) Versus Gemcitabine and Nab-Paclitaxel (GN) in Patients with Advanced Pancreatic Cancer: Multi-Institutional Canadian Sites Experience
Presenter: Neha Papneja
Session: Poster Display session 2
Resources:
Abstract
1166 - Effect of prior cancer on survival outcomes for patients with pancreatic adenocarcinoma
Presenter: Chaobin He
Session: Poster Display session 2
Resources:
Abstract
1169 - Association of combination of irreversible electroporation ablation and chemotherapy with outcomes of locally advanced pancreatic cancer: a large cohort study
Presenter: Chaobin He
Session: Poster Display session 2
Resources:
Abstract
1222 - Results from phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) in combination with gemcitabine plus nab-paclitaxel as first-line treatment of unresectable pancreatic cancer
Presenter: Yusuke Hashimoto
Session: Poster Display session 2
Resources:
Abstract
1698 - Multicenter retrospective study of gemcitabine plus nab-paclitaxel for elderly patients with advanced pancreatic cancer
Presenter: Masato Ozaka
Session: Poster Display session 2
Resources:
Abstract
2424 - Irinotecan Combined with Oxaliplatin and S1 in Patients with Metastatic Pancreatic Adenocarcinoma
Presenter: Keke Nie
Session: Poster Display session 2
Resources:
Abstract
2885 - Cancer-associated thrombosis in patients with pancreatic cancer and its correlation with plasma tissue factor level: A Japanese prospective cohort study
Presenter: Satoshi Kobayashi
Session: Poster Display session 2
Resources:
Abstract
3702 - A Phase I/Ib, multi-center trial of ARQ-761 (Beta-Lapachone) with gemcitabine/nab-Paclitaxel in patients with advanced pancreatic cancer
Presenter: Muhammad Beg
Session: Poster Display session 2
Resources:
Abstract
5185 - Systemic administration of the hyaluronidase-expressing oncolytic adenovirus VCN-01 in patients with advanced or metastatic pancreatic cancer: first-in-human clinical trial
Presenter: Rocio Garcia-Carbonero
Session: Poster Display session 2
Resources:
Abstract