First-line treatment with CET/PAN vs. BEV in elderly patients with RAS WT mCRC: A multicenter real-world observational study by the Japanese Society for Cancer of the Colon and Rectum

Elderly patients are often underrepresented in clinical trials for metastatic colorectal cancer (mCRC), and there is limited evidence on the efficacy of anti-epidermal growth factor antibody (cetuximab or panitumumab [CET/PAN]) or bevacizumab (BEV) in this population. We aimed to compare the efficacy of these regimens in elderly patients with unresectable or metastatic RAS wild-type (WT) left-sided colorectal cancer.

We retrospectively analyzed data of patients who received CET/PAN or BEV plus 5-fluorouracil-based doublet chemotherapy as first-line treatment for RAS WT mCRC at 24 Japanese institutions between January 2013 and December 2016. Progression-free survival (PFS) and overall survival (OS) in left-sided mCRC were compared between the BEV and CET/PAN in a non-elderly cohort ( < 70 years) and an elderly cohort (≥70 years) by multivariate Cox regression analysis.

Of 935 potentially eligible patients, 722 with left-sided mCRC were included in this study. The non-elderly cohort included 562 patients (77.8%), and the elderly cohort included 160 patients (22.2%). In non-elderly patients, PFS (median 13.3 months [12.2-15.0] vs. 12.4 months [95% CI 10.7-14.2]; adjusted HR 0.89 [0.75-1.06]) and OS (median 36.8 months [33.6-40.1] vs 30.9 months [27.2-38.0]; adjusted HR 1.01 [0.82-1.24]) were similar between CET/PAN and BEV. In contrast, PFS was inferior in elderly patients receiving CET/PAN compared with BEV (13.0 months [10.1-15.5] vs 10.2 months [6.7-11.0]; adjusted HR 0.66 [0.48-0.92]). Moreover, additional analysis by age suggested a worsening of PFS with CET/PAN compared with BEV in patients aged 70-74 years (HR 0.78 [0.64-0.96]) and 75 years or older (HR 0.49 [0.28-0.87]). OS was also shorter in elderly patients receiving CET/PAN than in those receiving BEV (median OS of 33.0 months [26.5-38.2] vs 21.8 months [15.6–31.4]; adjusted HR 0.55 [0.37-0.80]). Discontinuation due to adverse events was more common in patients receiving CET/PAN than in those receiving BEV, especially in the elderly cohort (non-elderly cohort, 9.4% vs 5.4%; elderly cohort, 23.9% vs 11.9%).The proportion of patients undergoing conversion surgery was higher in the CET/PAN group than in the BEV group regardless of age, but the proportion of conversion surgery was lower in the elderly cohort (non-elderly cohort, 22.5% vs 15.7%; elderly cohort, 10.9% vs 5.5%).

CET/PAN may have limited efficacy and may be more toxic in elderly patients with RAS WT colorectal cancer. These findings should be considered when treating elderly patients with RAS WT colorectal cancer, and appropriate management of side effects is needed for elderly patients receiving CET/PAN.

The authors.

Has not received any funding.

A. Takashima: Speaker Bureau / Expert testimony: Takeda, Ono Pharmaceutical, Lilly; Research grant / Funding (institution): Ono Pharmaceutical. K. Yamazaki: Honoraria (self): Chugai Pharma, Takeda, Taiho; Research grant / Funding (institution): Taiho Pharmaceutical. T. Moriwaki: Speaker Bureau / Expert testimony: Merk Serono, Chugai, Takeda; Research grant / Funding (institution): Chugai, Takeda. N. Sugimoto: Research grant / Funding (institution): MSD, Daiichi-Sankyo, Pfizer. H. Yasui: Honoraria (self): Daiichi Sankyo, Ono Pharmaceutical, Taiho Pharmaceutical, Chugai Pharma, Bristol-Myers Squibb Japan, TERUMO, Eli Lilly Japan, Merk Biopharma, Yakult Honsha, Bayer Yakuhin, Takeda Pharmaceutical; Research grant / Funding (self): MSD, Ono Pharmaceutical, Daiichi Sankyo, Astellas Pharma, Amgen. T. Esaki: Honoraria (self): Daiichi Sankyo, Chugai, Taiho; Research grant / Funding (institution): MSD, Chugai, Daiichi Sankyo,. A. Tsuji: Speaker Bureau / Expert testimony: Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan Co., ; Research grant / Funding (institution): Taiho Pharmaceutical Co., Ltd., Sanofi Corporation, Ono Pharmaceutical Co.,. K. Shinozaki: Honoraria (self): TAIHO Phamaceutical Co., Ltd, DAIICHI SANKYO Co., Ltd, EISAI Co., Ltd.. All other authors have declared no conflicts of interest.