Chemotherapy plus bevacizumab as an optimal first-line therapeutic treatment for patients with right-sided metastatic colon cancer: a meta-analysis of first-line clinical trials

You, Xia-Hong; Jiang, Yulin; Zhou, Fang; Sun, Fan; Li, Yao; Wang, Wei; Xia, Zijin; Wang, Xiaozhong

doi:10.1136/esmoopen-2019-000605

Cited by 23 publications

(18 citation statements)

References 49 publications

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“…When pathological classification was included, we found that patients with mCRC with MA/MC, either left‐ or right‐side mCRC could benefit from bevacizumab‐based therapy. In another study, 29 You et al demonstrated that bevacizumab‐based treatment is an optimal first‐line therapy for right‐sided RAS‐wild mCRC, which is consistent with the outcome of our study that bevacizumab plus chemotherapy is the best regimen for patients with right‐side mCRC, with either MA/MC or NMA.…”

Section: Discussionsupporting

confidence: 92%

First‐line therapy of bevacizumab plus chemotherapy versus cetuximab plus chemotherapy for metastatic colorectal cancer patients with mucinous adenocarcinoma or mucinous component

et al. 2021

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Background To compare the efficacy of first‐line bevacizumab plus chemotherapy with cetuximab plus chemotherapy based on the stratification of metastatic colorectal cancer (mCRC) patients with mucinous adenocarcinoma (MA) or mucinous component (MC). Methods A retrospective study involving all mCRC patients receiving first‐line bevacizumab‐based or cetuximab‐based chemotherapy at our hospital from September 2013 to January 2020 was conducted. Overall survival (OS), progression‐free survival (PFS), and objective response rate (ORR) were compared between the cetuximab‐chemotherapy group and the bevacizumab‐chemotherapy group on the basis of the conventional pathological classification of MA or MC. Results A total of 620 patients with mCRC were included in our study, consisting of 141 (22.7%) patients with MA/MC and 479 (77.3%) patients with non‐mucinous adenocarcinoma (NMA). In the MA/MC cohort, patients who were treated with bevacizumab‐based chemotherapy were associated with significantly better OS than those treated with cetuximab‐base chemotherapy (30.0 vs. 26.3 months, p = 0.002), irrespective of tumor sites. The efficacy of bevacizumab‐based chemotherapy was higher in nearly all subgroups as shown in the subgroup analysis. In the NMA cohort, median OS was better in the cetuximab plus chemotherapy group than that in the bevacizumab plus chemotherapy group (32.2 vs. 27.0 months, p = 0.005) for left‐side mCRC patients, whereas OS was significantly longer in the bevacizumab plus chemotherapy group for right‐side mCRC patients (26.0 vs. 20.9 months, p = 0.013). Conclusion Conventional pathological classification (e.g. MA/MC) should be considered when tailoring the individualized optimal treatment for mCRC. Bevacizumab plus chemotherapy as first‐line therapy may be the optimal option for patients with MA/MC.

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Section: Discussionsupporting

confidence: 92%

First‐line therapy of bevacizumab plus chemotherapy versus cetuximab plus chemotherapy for metastatic colorectal cancer patients with mucinous adenocarcinoma or mucinous component

et al. 2021

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“…There are also suggestions in the literature that chemosensitivity is important in predicting survival, and that there may be a differing chemosensitivity profile according to PTL. In their meta-analysis of 16 first-line trials evaluating the efficacy of chemotherapy alone vs chemotherapy with targeted biologics in patients with unresectable metastatic CRC, You et al[ 64 ] found survival of patients with right sided CRC was inferior to those with left in patients receiving chemotherapy alone, implying that right-sided tumours overall are less chemosensitive. This finding is supported by Yamashita et al[ 26 ] found that r -CRCLM were independently associated with “minor pathological response” (defined as cancer cells accounting for ≥ 50% of residual cells), and were thus less sensitive to chemotherapy with worse RFS and OS.…”

Section: Discussionmentioning

confidence: 99%

“…This difference is maintained after the addition of well-established antiangiogenic biologics. You et al[ 64 ] found inferior survival in patients with r -CRCLM receiving chemotherapy and bevacizumab compared with l -CRCLM. Zheng et al[ 31 ] studied the effect of cetuximab as an addition to chemotherapy in KRAS wild-type patients with initially unresectable hepatic metastases.…”

Section: Discussionmentioning

confidence: 99%

Impact of primary tumour location on colorectal liver metastases: A systematic review

Bingham¹,

Shetye²,

Suresh³

et al. 2020

WJCO

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BACKGROUND Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide. Despite significant advances in screening, surgical management and adjuvant therapies, average 5-year survival seldom exceeds 60% in most developed nations. Metastatic disease represents the primary cause of mortality in patients with CRC, and the liver is the most common location for distant tumour spread. Up to 25% of patients are found to have synchronous liver metastases at the time of diagnosis and a further 30%-40% will develop metachronous disease in the course of follow-up. It has been suggested that primary tumour location [right side versus left side, primary tumour location (PTL)] can influence oncological outcomes in this patient group and that this should be considered in prognostic models and therapeutic decision-making algorithms. This suggestion is not universally accepted and there have been conflicting reports in the literature to date. AIM To provide a comprehensive summary of the available evidence regarding the impact of PTL on oncological outcomes in patients with colorectal cancer liver metastases (CRCLM). METHODS MEDLINE, EMBASE and COCHRANE were searched for relevant publications using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Data on oncological outcomes was then extracted from full text articles that met the predefined inclusion criteria. RESULTS A total of 41 studies were identified that met predefined inclusion criteria for this review. In 21 out of 38 studies that provided data on overall survival, a statistically significant improvement in overall survival was reported in patients with left sided primary tumours. These studies included a total of 13897 patients compared with 4306 patients in the studies that did not show a significant difference. Eight studies noted a similar trend towards improved disease-free or progression-free survival. Several authors observed distinct patterns of relapse after treatment of hepatic metastases according to PTL; for example hepatic recurrence after treatment of CRCLM appears to occur more aggressively with right-sided CRC. CONCLUSION Taken together, the findings of the present review indicate that PTL may have a role as an independent prognostic factor when determining treatment and disease surveillance strategies in CRC. The mechanisms responsible for this variation remain poorly understood, but are likely to relate to molecular, histological and embryological differences, as well as inherent differences in therapeutic sensitivity.

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“…A large amount of data consistently shows that metastatic CRC (mCRC) cases with left-sidedness derive meaningful benefit from anti-epidermal growth factor receptor antibody (9)(10)(11). Our previous studies also imply that the prognosis of bevacizumab-treated left-sided mCRC patients is better than the counterpart (12,13). These findings reveal that tumor laterality can affect and predict the efficacy of target therapy within the advanced disease.…”

Section: Introductionmentioning

confidence: 52%

High-Grade Inflammation Attenuates Chemosensitivity and Confers to Poor Survival of Surgical Stage III CRC Patients

et al. 2021

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Background: Heterogeneous clinical and molecular characteristics are reported in colorectal cancer (CRC) with different tumor laterality. However, the outcome of left- and right-sided patients with stage I–III CRC and the role of chronic inflammation in survival differences between them remain unclear.Method: A prospective study including 1,181 surgical patients with stage I–III CRC was carried out to investigate the involvement of circulating fibrinogen-to-pre-albumin (Alb) ratio (FPR) and primary tumor sidedness in the clinical outcome of those patients. We further investigated the effect of FPR on adjuvant chemotherapy response and recurrence in stage III patients.Results: Our study showed that the right tumor location was significantly associated with poor recurrence-free survival (RFS) (p = 0.04, adjusted HR = 1.41, 95% CI = 1.02–1.94) and overall survival (OS) (p = 0.04, adjusted HR = 1.55, 95% CI = 1.01–2.38) only in the stage III disease. In these patients, T4 stage distribution (83.39 vs. 70.94%, p < 0.01) within right-sided cases was significantly higher than left-sided patients. Moreover, preoperative FPR within right-sidedness (p < 0.01), T4 stage (p < 0.05), and large cancer bulk (≥5 cm) (p < 0.05) subgroups was significantly elevated compared to their counterparts, and it was gradually rising following the increased cancer bulk (p trend < 0.01). High-FPR distribution (52.30 vs. 27.00%, p < 0.01) within right-sided patients with the stage III disease was significantly higher than that in the left-sided cases. RFS (plog−rank < 0.01) and OS (plog−rank < 0.01) of the high-FPR patients were extremely inferior to the low-FPR cases, and the significant associations were observed when they were adjusted by other confounders including primary tumor location (p < 0.01, adjusted HR = 1.96, 95% CI = 1.42–2.70 for RFS; p < 0.01, adjusted HR = 2.44, 95% CI = 1.59–3.75 for OS). Additionally, RFS of adjuvant chemotherapy-treated high-FPR patients was superior to the patients without chemotherapy (plog−rank = 0.01) but was inferior to the low-FPR patients undergoing the treatment, especially in the 5-FU- and XELOX-treated subgroup.Conclusion: These findings indicate that chronic high-grade inflammation weakens chemotherapy efficacy and contributes to the poor prognosis of stage III surgical CRC patients.

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Chemotherapy plus bevacizumab as an optimal first-line therapeutic treatment for patients with right-sided metastatic colon cancer: a meta-analysis of first-line clinical trials

Cited by 23 publications

References 49 publications

First‐line therapy of bevacizumab plus chemotherapy versus cetuximab plus chemotherapy for metastatic colorectal cancer patients with mucinous adenocarcinoma or mucinous component

First‐line therapy of bevacizumab plus chemotherapy versus cetuximab plus chemotherapy for metastatic colorectal cancer patients with mucinous adenocarcinoma or mucinous component

Impact of primary tumour location on colorectal liver metastases: A systematic review

High-Grade Inflammation Attenuates Chemosensitivity and Confers to Poor Survival of Surgical Stage III CRC Patients

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