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
5458 - Baseline characteristics from CLARINET FORTE: Evaluating lanreotide autogel (LAN) 120 mg every 14 days in patients with progressive pancreatic or midgut neuroendocrine tumours during a standard first-line LAN regimen.
Presenter: Philippe Ruszniewski
Session: Poster Display session 2
Resources:
Abstract
1234 - Analysis of PD-1/PD-L1 blockade biomarker and immune infiltrates in Gastroenteropancreatic neuroendocrine carcinoma
Presenter: Jia Zhang Xing
Session: Poster Display session 2
Resources:
Abstract
1517 - Diabetes Is Associated With Pancreatic Neuroendocrine Tumors Growth and Metastasis
Presenter: Zhiyao Fan
Session: Poster Display session 2
Resources:
Abstract
2145 - Investigation of the reclassification of G1/G2 pancreatic neuroendocrine neoplasms by WHO 2017 classification
Presenter: Takahiro Yokose
Session: Poster Display session 2
Resources:
Abstract
3134 - Treatment with somatostatin analogues after radiopeptide therapy
Presenter: Daria Handkiewicz Junak
Session: Poster Display session 2
Resources:
Abstract
2191 - Safety and Tolerability of Surufatinib in Western Patients with Solid Tumors
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3253 - The impact of tumour absorbed dosimetry with survival outcomes after peptide receptor radionuclide therapy in metastatic neuroendocrine tumours.
Presenter: Rahul Ladwa
Session: Poster Display session 2
Resources:
Abstract
3581 - Opportunist and Serious Infections in Patients with Neuroendocrine Tumors Treated With Everolimus: A Multicenter Study of Real World Patients
Presenter: Carine Mauro
Session: Poster Display session 2
Resources:
Abstract
5374 - Establishment of Prognostic Nomogram Based on the Metastatic Lymph Nodes Ratio for Patients with Gastric Neuroendocrine Tumour
Presenter: yaobin lin
Session: Poster Display session 2
Resources:
Abstract
3951 - Neutrophil-lymphocyte ratio as an independent predictive factor in Neuroendocrine Neoplasms
Presenter: Sofia Ferreira
Session: Poster Display session 2
Resources:
Abstract