Abstract
The emerging debate between primary tumor location and clinical outcome of bevacizumab treated metastatic colorectal cancer (mCRC) continues. The aim of the present study is to investigate the association between the primary tumor location and clinical outcome of 115 mCRC patients receiving bevacizumab based treatment. A meta-analysis including 21 studies was carried out to confirm the conclusion. In our prospective study, we found that right-sided mCRC commonly occurred in older cases (p = 0.03) with multiple-site metastasis (p = 0.03). Progression-free survival (PFS) of the left-sided patients undergoing bevacizumab plus a FOLFIRI regimen was superior to the right-sided cases (p = 0.03, crude HR = 0.31, 95%CI = 0.11–0.87; adjusted HR = 0.21, 95%CI = 0.06–0.66). The meta-analysis confirmed that efficacy of bevacizumab-based treatment in left-sided mCRC patients was better than the right-sided cases in the overall population (Ph = 0.24, combined OR = 1.36, 95%CI = 1.07–1.72), RAS/BRAF wild-type (Ph = 0.19, combined OR = 1.66, 95%CI = 1.17–2.34), clinical trial (Ph = 0.23, combined OR = 1.42, 95%CI = 1.07–1.88), Caucasian population (Ph = 0.18, combined OR = 1.37, 95%CI = 1.02–1.85) and first-line (Ph = 0.19, combined OR = 1.48, 95%CI = 1.13–1.96) subgroups. Improved survival of bevacizumab plus chemotherapy treated left-sided mCRC patients was observed in the overall population [Ph < 0.01, combined MSR = 1.09, 95%CI = 1.00–1.18 for PFS; Ph < 0.01, combined MSR = 1.24, 95%CI = 1.13–1.36 for overall survival (OS)], especially in the RAS/BRAF wild-type (Ph = 0.09, combined MSR = 1.10, 95%CI = 1.03–1.19 for PFS; Ph = 0.02, combined MSR = 1.34, 95%CI = 1.21–1.49 for OS). These findings indicate that primary tumor sidedness can predict clinical outcome of bevacizumab-treated RAS/BRAF wild-type mCRC patients and the left-sided patients may benefit more from bevacizumab plus FOLFIRI.
Highlights
Colorectal cancer (CRC) is the fourth most commonly diagnosed malignancy and the second leading cause of cancer-related death worldwide [1]
We found that left-sided metastatic CRC (mCRC) patients could benefit more from bevacizumab plus FOLFIRI compared with its counterpart
Loupakis et al reported that clinical outcomes of both two-sided mCRC patients were improved by treatment with bevacizumab and chemotherapy [41]
Summary
Colorectal cancer (CRC) is the fourth most commonly diagnosed malignancy and the second leading cause of cancer-related death worldwide [1]. Clinical outcomes of the two inhibitor managed mCRC patients remain unsatisfactory in the clinic, with evidence showing that objective response rates (ORRs) and median progression-free survival (PFS) of cetuximab or bevacizumab-based chemotherapy are 59.6% and 10.5 months in KRAS-wild patients, and 62.1% and 9.5 months in the overall patient population [4, 5], respectively. Accumulating evidence has shown the significant differences in clinical characteristics, anatomic structure, embryological origin, and the genetic mutation profile between left- and right-sided CRC [6]. The latest clinical trials and meta-analyses confirmed that KRAS-wild patients with left-sided mCRC derived great benefit from EGFR-inhibitor contained treatment [12, 13], and the inhibitor has been recommended as a first-line therapeutic treatment for patients in the 2017 National Comprehensive Cancer Network guideline [14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
