Abstract 3888
Background
The C-cubed study investigates the optimal treatment strategy in patients with untreated metastatic colorectal cancer (mCRC). We tested the superiority of a sequential treatment of FP+BEV followed by OX+FP+BEV (arm A: OX “wait & go”) at first progression to a combination treatment of OX+FP+BEV (arm B: OX “stop & go”), trial information: UMIN000015405.
Methods
The Primary endpoint was time-to-failure of strategy (TFS). A target sample size of 304 patients was considered sufficient to validate an expected Hazard Ratio (HR) for TFS of arm A compared with arm B with 80% power and 2-sided 5% α in case of a true HR value of < 0.69. Secondary endpoints included overall response rate, overall survival (OS), progression-free survival, and safety.
Results
Between Dec 2014 and Sep 2016, 311 patients were enrolled, and 302 patients were randomized either to receive the arm A (n = 151) or B (n = 151) as a full analysis set (FAS). Superiority of TFS in the arm A was established in this study (HR, 0.475; 95% CI, 0.362–0.623; p < 0.0001). OSs in the arms A and B were not considered significantly different (HR, 0.930; 95% CI, 0.666–1.298). The patient population was predominantly positive for RAS mutant tumors (RAS MT) compared with that for RAS wild-type tumors (RAS WT), but this did not confer any clinical disadvantage in TFS to either arms (see table for details). We will present additional data associated with RAS status and differences between capecitabine and 5-fluorouracil at the meeting.Table:
571P
Table | Endpoint | Arm A, “wait & go” (n = 151) Months (95%CI) | Arm B, “stop & go” (n = 151) Months (95%CI) | p-value (log rank) |
---|---|---|---|---|
TFS (FAS) | 15.2 (12.5 – 17.2) | 7.6 (6.2 – 9.5) | <.0001 | |
OS (FAS) | 27.5 (24.4 – 32.7) | 29.4 (24.1 – 36.0) | 0.6692 | |
Factor | RAS WT (n = 112) Months (95%CI) | RAS MT (n = 167) Months (95%CI) | p-value (log rank) | |
TFS | Arm A | 14.0 (11.2 – 19.0) | 15.3 (12.4 – 17.2) | 0.3126 |
Arm B | 7.8 (7.0 – 10.5) | 7.4 (5.2 – 9.6) | 0.1615 | |
OS | Arm A | 27.5 (22.6 – NC) | 28.0 (23.4 – 32.7) | 0.3143 |
Arm B | 34.7 (24.5 – NC) | 24.3 (19.1 – 32.8) | 0.0265 |
Conclusions
The sequential “wait & go” strategy for OX was superior in TFS compared with the combinational “stop & go” accompanying with the equal survival benefit of nearly 30 months. Thus, the sequential approach with FP+BEV followed by OX is deemed an acceptable treatment strategy for patients with mCRC.
Clinical trial identification
UMIN000015405.
Editorial acknowledgement
Legal entity responsible for the study
Japan South West Oncology Group (JSWOG).
Funding
Chugai Pharmaceutical Co., Ltd.
Disclosure
T. Nagasaka: Speaker Bureau / Expert testimony: Eli Lilly Japan. Y. Shindo: Research grant / Funding (institution): Chugai; Research grant / Funding (institution): MSD; Research grant / Funding (self): Ono; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Lilly. A. Tsuji: Honoraria (institution): Daiichi Sankyo; Honoraria (institution), Speaker Bureau / Expert testimony: Taiho Pharmaceutical; Honoraria (institution), Speaker Bureau / Expert testimony: Chugai Pharma; Honoraria (institution), Speaker Bureau / Expert testimony: Merck Serono; Honoraria (institution), Speaker Bureau / Expert testimony: Takeda Pharmaceutical; Honoraria (institution): Bristol-Myers Squibb Japan. Y. Tsuji: Honoraria (institution): Bayer Co. Ltd; Honoraria (institution): Merck Serono Co. Ltd; Honoraria (institution): Eli Lilly Japan; Honoraria (institution): Chugai Pharmaceutical Co. Ltd; Honoraria (institution): Taiho Pharmaceutical Co. Ltd; Honoraria (institution): Ono Pharmaceutical Co. Ltd; Honoraria (institution): Takeda Pharmaceutical Co. Ltd; Honoraria (institution): Medicon Co. Ltd. H. Mishima: Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd. All other authors have declared no conflicts of interest.
Resources from the same session
2786 - Development of a living organoid biobank derived from colorectal cancer patients: towards personalized medicine
Presenter: Federica Papaccio
Session: Poster Display session 2
Resources:
Abstract
3351 - Microsatellite Instability Detection in Colorectal Cancer: 44-Center Comparison between the Idylla MSI Assay and Routine Molecular and Immunohistochemistry Tests on Formalin-Fixed Paraffin-Embedded Tissue
Presenter: Xavier Matias-guiu
Session: Poster Display session 2
Resources:
Abstract
4901 - Expression profile of EPHB3 and its prognostic significance in colorectal cancer progression (Running head: Prognostic value of EPHB3 in colorectal cancers)
Presenter: Bogun Jang
Session: Poster Display session 2
Resources:
Abstract
5030 - A pan-ErbB family inhibitor, AF8c, promotes apoptosis by DR5/Nrf2 activation via ROS in colorectal cancer cells
Presenter: Soyeon Jeong
Session: Poster Display session 2
Resources:
Abstract
5053 - Frequent BRAF, GNAS and SMAD4 mutations identified in Colorectal Mucinous Carcinomas
Presenter: Sun Mi Lee
Session: Poster Display session 2
Resources:
Abstract
5220 - Impact of CCL4 knockout using CRISPR Cas-9 technology on colorectal tumor progression
Presenter: Roba Barakat
Session: Poster Display session 2
Resources:
Abstract
5330 - Independent clinical validation of a gene expression profile to predict benefit of 5-FU in metastatic colorectal cancer
Presenter: Ida Buhl
Session: Poster Display session 2
Resources:
Abstract
5515 - WRN mutated Colorectal Cancer (CRC) is characterized by a distinct molecular and immunological profile
Presenter: Andreas Seeber
Session: Poster Display session 2
Resources:
Abstract
5716 - Mutation analysis of B2M gene in colorectal cancer patients with microsatellite instability
Presenter: Ivana Kašubová
Session: Poster Display session 2
Resources:
Abstract
870 - Selective Wnt/β-catenin small-molecule inhibitor CWP232228 impairs tumor growth of colon cancer
Presenter: Jin Young Kim
Session: Poster Display session 2
Resources:
Abstract