Efficacy of Oxaliplatin-based Chemotherapy+Bevacizumab as First-line Treatment for Advanced Colorectal Cancer

Petrelli, Fausto; Coinu, Andrea; Ghilardi, Mara; Cabiddu, Mary; Zaniboni, Alberto; Barni, Sandro

doi:10.1097/coc.0b013e3182a2d7b8

Cited by 27 publications

(19 citation statements)

References 28 publications

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“…From these new data, we could see several points clearly. First, as expected, significantly better survival was observed in both black and white patients who were diagnosed in 2004 or after than those diagnosed before 2004 (Supplementary Figure S4), which demonstrates the effectiveness of the use of oxaliplatin plus fluorouracil/capecitabine and target therapy in colorectal cancer treatment, and is consistent with the numerous published reports 32–38 . Second, the racial survival disparity was smaller in the patients diagnosed in 2004 or after than diagnosed before 2004, indicating the use of oxaliplatin and/or bevacizumab helped to reduce the racial survival disparity (Supplementary Table S10, e.g., in demographic match, the two-, three-, and five-year survival disparity was 8.3%, 8.5%, and 9.6%, respectively, in the patients diagnosed before 2004, whereas 5.6%, 6.5%, and 7.1%, respectively, in those diagnosed in 2004 or after).…”

Section: Resultssupporting

confidence: 88%

Effects of Cancer Stage and Treatment Differences on Racial Disparities in Survival From Colon Cancer: A United States Population-Based Study

et al. 2016

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Background & Aims We evaluated differences in treatment of black vs white patients with colon cancer and assessed their effects on survival, based on cancer stage. Methods We collected data from the Surveillance, Epidemiology and End Results (SEER)-Medicare database and identified 6190 black and 61,951 white patients with colon cancer diagnosed from 1998 through 2009 and followed through 2011. Three sets of 6190 white patients were sequentially matched, using a minimum distance strategy, to the same set of 6190 black patients based on demographic (age, sex, diagnosis year, and SEER registry), tumor presentation (demographic plus comorbidities, tumor stage, grade, and size), and treatment (presentation plus therapies) variables. We conducted sensitivity analyses to explore the effects of socioeconomic status in a sub-cohort that included 2000 randomly selected black patients. Racial differences in treatment were assessed using a logistic regression model; their effects on racial survival disparity were evaluated using Kaplan-Meier method and Cox proportional hazards model. Results After patients were matched for demographic variables, the absolute 5 y difference in survival between black and white patients was 8.3% (white, 59.2% 5 y survival; blacks, 50.9% 5 y survival) (P<.0001); this value decreased significantly, to 5.0% (P<.0001), after patients were matched for tumor presentation, and decreased to 4.9% (P<.0001) when patients were matched for treatment. Differences in treatment therefore accounted for 0.1% of the 8.3% difference in survival between black and white patients. After patients were matched for tumor presentation, racial disparities were observed in almost all types of treatment; the disparities were most prominent for patients with advanced-stage cancer (stages III or IV, up to 11.1% difference) vs early-stage cancer (stages I or II, up to 4.3% difference). After patients were matched for treatment, there was a greater reduction in disparity for black vs white patients with advanced-stage compared with early-stage cancer. In sensitivity analyses, the 5 y racial survival disparity was 7.7% after demographic match, which was less than 8.3% observed in the complete cohort. This reduction was likely due to the differences between the sub-cohort and the complete cohort in those variables that were not included in the demographic match. This value was reduced to 6.5% (P=.0001) after socioeconomic status was included in the demographic match. The difference decreased significantly to 2.8% (P=.090) after tumor presentation match, but was not further reduced after treatment match. Conclusions We observed significant disparities in treatment and survival of black vs white patients with colon cancer. The disparity in survival appears to have been more strongly affected by tumor presentation at diagnosis than treatment. The effects of treatment differences on disparities in survival were greater for patients with advanced-stage, vs early-stage, cancer.

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Section: Resultssupporting

confidence: 88%

Effects of Cancer Stage and Treatment Differences on Racial Disparities in Survival From Colon Cancer: A United States Population-Based Study

et al. 2016

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“…This same association was found active also in pre-treated patients, as shown in another report pooling data from 11 studies [13]. Likewise, an oxaliplatin-based regimen was initially found to be more active when combined to bevacizumab [7]; subsequent pooled analysis confirmed this finding, too [14]. Altogether, these data confirm the improvement in objective response, progression-free and overall survival when bevacizumab is added to a doublet chemotherapy [15], with even more promising results reported in association with a triplet backbone [16,17].…”

Section: Tumour Neo-angiogenesis and Bevacizumabsupporting

confidence: 62%

Use of Bevacizumab in the Management of Potentially Resectable Colorectal Liver Metastases: Safety, Pathologic Assessment and Benefit

Innominato

Adam

2016

Curr Colorectal Cancer Rep

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Liver metastases are a frequent and commonly lethal complication of colorectal cancer. Surgical resection of limited liver disease offers currently the best chance of longterm survival, but surgery is not feasible for a rather significant proportion of patients with hepatic metastases. Despite the overall improvement in the medical management of patients with metastatic colorectal cancer, whose median survival has been substantially prolonged with the availability of novel drugs, long-term outcomes remain rather poor if a combined onco-surgical strategy cannot be implemented. Nonetheless, newer chemotherapy schedules have become more frequently, rapidly and deeply active, improving hepatic lesions' downsizing, hence extending the pool of patients amenable to secondary liver surgery. Here, we summarize available data on the efficacy and safety of bevacizumab, an anti-VEGF monoclonal antibody indicated for the treatment of metastatic colorectal cancer, as a conversion chemotherapeutic option in the management of patients with liver metastases.

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“…In addition, another recent meta-analysis conducted in 2015 focused on the survival benefits of chemotherapy alone, showing that oxaliplatin and capecitabine or infusional/bolus 5-fluorouracil-based chemotherapy plus bevacizumab (XELOC + B and FOLFOX + B) are active,46 approved first-line combination therapies for advanced CRC with improved OS (23.7 months) and PFS (10.3 months) when bevacizumab is part of the combination. However, the included retrospective studies were not homogeneous for site, extent of disease, performance status, comorbidities, or KRAS status (mutant or wild type).…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of outcomes of patients with stage IV colorectal cancer managed with chemotherapy/radiochemotherapy with and without primary tumor resection

Lee¹,

Ou²,

Hu³

et al. 2016

OTT

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BackgroundColorectal cancer is the third leading cause of death worldwide. Currently, novel chemotherapeutic agents are first-line therapy for unresectable stage IV colorectal cancer, while benefits of noncurative primary tumor resection in advanced disease remain debatable.ObjectiveThis meta-analysis evaluated outcomes of patients with unresectable stage IV colorectal cancer receiving systemic chemotherapy with or without primary tumor resection.Materials and methodsA database search of PubMed and Cochrane Library databases identified 167 studies that were screened for relevance. After 119 were excluded, 48 were assessed for eligibility and 26 were included for meta-analysis, including 24 retrospective studies, one prospective study, and one randomized, controlled trial. Extracted data included patient demographics (age, sex), clinical data (tumor stage, metastasis), targeted therapy agents, and surgical data (with/without tumor resection). Patients’ overall and progression-free survival was compared between groups with/without primary tumor resection.ResultsThe 26 studies included 43,903 patients with colorectal cancer, with 29,639 receiving chemotherapy/radiotherapy plus primary tumor resection, and 14,264 managed medically with chemotherapy/chemoradiotherapy alone without primary tumor resection. Patients receiving primary tumor resection plus chemotherapy/radiotherapy had longer overall survival (hazard ratio [HR 0.59], 95% confidence interval [CI] 0.51–0.68; P<0.001), with significant differences in overall survival between patients with and without primary tumor resection (HR 0.58, 95% CI 0.49–0.68; P<0.001). Longer overall survival was also found among patients receiving primary tumor resection who were treated with bevacizumab/cetuximab targeted therapy agents (HR 0.63, 95% CI 0.46–0.86; P=0.003). Patients from three studies who received primary tumor resection had longer progression-free survival (HR 0.73, 95% CI 0.58–0.91; P=0.005). Results are limited by retrospective data, inconsistent complications data, and publication bias.ConclusionStudy results support primary tumor resection in stage IV colorectal cancer, but significant biases in studies suggest that randomized trials are warranted to confirm findings.

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Efficacy of Oxaliplatin-based Chemotherapy+Bevacizumab as First-line Treatment for Advanced Colorectal Cancer

Cited by 27 publications

References 28 publications

Effects of Cancer Stage and Treatment Differences on Racial Disparities in Survival From Colon Cancer: A United States Population-Based Study

Effects of Cancer Stage and Treatment Differences on Racial Disparities in Survival From Colon Cancer: A United States Population-Based Study

Use of Bevacizumab in the Management of Potentially Resectable Colorectal Liver Metastases: Safety, Pathologic Assessment and Benefit

Meta-analysis of outcomes of patients with stage IV colorectal cancer managed with chemotherapy/radiochemotherapy with and without primary tumor resection

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