A randomized phase III trial of mFOLFOX7 or CapeOX plus bevacizumab versus 5-FU/l-LV or capecitabine plus bevacizumab as initial therapy in elderly patients with metastatic colorectal cancer: JCOG1018 study (RESPECT).

Authors

Tetsuya Hamaguchi

Tetsuya Hamaguchi

Department of Medical Oncology, Saitama Medical University International Medical Center, Saitama, Japan

Tetsuya Hamaguchi , Atsuo Takashima , Junki Mizusawa , Yasuhiro Shimada , Fumio Nagashima , Masahiko Ando , Hitoshi Ojima , Tadamichi Denda , Jun Watanabe , Katsunori Shinozaki , Hideo Baba , Masako Asayama , Tadao Fukushima , Toshiki Masuishi , Ken Nakata , Shunsuke Tsukamoto , Hiroshi Katayama , Kenichi Nakamura , Haruhiko Fukuda , Yukihide Kanemitsu

Organizations

Department of Medical Oncology, Saitama Medical University International Medical Center, Saitama, Japan, Department of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan, JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan, Clinical Oncology Division, Kochi Health Sciences Center, Kochi, Japan, Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan, Department of Advanced Medicine, Nagoya University Hospital, Aichi, Japan, Gastrointestinal Surgery, Gunma Prefectural Cancer Center, Gunma, Japan, Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan, Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan, Division of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima, Japan, Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan, Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan, Division of Surgery, Saiseikai Yokohama Nanbu Hospital, Yokohama, Japan, Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan, Department of Surgery, Sakai City Medical Center, Osaka, Japan, Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan, National Cancer Center Hospital, Tokyo, Japan, Japan Clinical Oncology Group Data Center, National Cancer Center Hospital, Tokyo, Japan, Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Tokyo, Japan

Research Funding

Other Government Agency

Background: It is uncertain if the addition of oxaliplatin (OX) to fluoropyrimidine plus bevacizumab (BEV) is suitable as initial therapy in elderly patients (pts) with metastatic colorectal cancer (MCRC). Therefore, we conducted a randomized controlled trial to confirm the superiority of the addition of OX in terms of progression-free survival (PFS). This JCOG trial was originally planned as a paralell study with NCCTG, but the NCCTG trial was terminated early. Methods: Key eligibility criteria included unresectable metastatic colorectal cancer, and histologically confirmed adenocarcinoma, aged 70-74 with PS 2 or 75 or older with ECOG PS 0-2. Eligible pts were randomized (1:1) to either no addition of OX or addition. Whether using 5-FU+levoleucovorin calcium (5-FU/l-LV) or capecitabine (CAPE) was declared before study entry; options included 5-FU/l-LV+BEV (C), CAPE+BEV (D), mFOLFOX7+BEV (E), or CapeOX+BEV (F). 5-FU/l-LV regimen omitted bolus 5-FU from the original sLV5FU regimen. The dose of CAPE was adjusted by estimated creatinine clearance. The primary endpoint was PFS. The planned sample size was 250 pts in total to detect a hazard ratio (HR) of 0.75, with a one-sided alpha of 5% and 70% power. The decision rule is that the primary endpoint is met, and the point estimate of HR of overall survival (OS) is less than 0.8. Results: Between Sep 2012 and Mar 2019, 251 pts were randomized. 125 pts were allocated to no addition of OX and 126 pts to addition. Median age was 79, aged 70-74/75-79/80-84/85+:5%/45%/37%/13%, PS 0/1/2:53%/39%/7%. Of 251 pts, 241 pts had PFS events and 223 pts had OS events. Median PFS (mPFS) was 9.4 months (M) (95%CI 8.3–10.3) in no addition of OX and 10.0M (9.0–11.2) in addition (HR 0.837, 90.5%CI [0.673–1.042], one-sided p = 0.086). Median OS was 21.3M (18.7-24.3) in no addition and 19.7M (15.5–25.5) in addition of OX (HR 1.054 [0.810–1.372]). Response rate was 29.5% (21.2-38.8) in no addition of OX and 47.7% (38.1-57.5) in addition. Proportion of pts whose EQ-5D scores improved from baseline to post-treatment in overall score did not differ (odds ratio 0.94 (0.51-1.75)). The deaths of 1 pt in no addition of OX and in 3 pts in addition were deemed treatment-related. Conclusions: The addition of OX has no survival benefit over no addition. OX was not recommended for elderly MCRC pts as initial therapy. Clinical trial information: UMIN000008866.


N
Median PFS (95% CI)
Median OS (95% CI)
No addition of OX
125
9.4M (8.3-10.3)
21.3M (18.7-24.3)
The addition of OX
126
10.0M (9.0-11.2)
19.7M (15.5-25.5)


HR:0.837 (0.648-1.033)

P = 0.086
HR:1.054 (0.810-1.372)
5FU/l-LV+BEV (C)
71
8.5M (6.3-9.9)
20.5M (16.7-23.3)
CAPE+BEV (D)
54
10.3M (9.1-11.8)
24.7M (18.4-29.6)
mFOLFOX7+BEV (E)
67
10.0M (9.0-11.6)
24.2M (16.6-27.8)
CapeOX+BEV (F)
59
10.0M (7.2-12.2)
16.4M (11.8—25.5)

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Abstract Details

Meeting

2022 ASCO Gastrointestinal Cancers Symposium

Session Type

Oral Abstract Session

Session Title

Oral Abstract Session C: Cancers of the Colon, Rectum, and Anus

Track

Colorectal Cancer,Anal Cancer

Sub Track

Therapeutics

Clinical Trial Registration Number

UMIN000008866

DOI

10.1200/JCO.2022.40.4_suppl.010

Abstract #

10

Abstract Disclosures