Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases

Pietrantonio, Filippo; Cotsoglou, Christian; Fucà, Giovanni; Vullo, Salvatore Lo; Nichetti, Federico; Milione, Massimo; Coppa, Jorgelina; Vaiani, Marta; Alessi, Alessandra; Prisciandaro, Michele; Busset, Michele Droz dit; Morano, Federica; Corallo, Salvatore; Lazzati, Silvia; Antista, Maria; Mennitto, Alessia; Randon, Giovanni; Raimondi, Alessandra; Belfiore, Antonino; Padovano, Barbara; Perrone, Federica; Mariani, Luigi; Bartolomeo, Maria Di; Braud, Filippo de; Mazzaferro, Vincenzo

doi:10.1016/j.clcc.2018.11.004

Cited by 7 publications

(4 citation statements)

References 39 publications

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“… 22-24 However, a systematic review and meta-analysis, as well as a phase II single-center study, have shown that pre-operative bevacizumab plus chemotherapy led to increased pathologic response that was associated with better survival outcomes in patients with mCRC. 22 , 24 Together with the results from our study, these data highlight the need to evaluate treatment efficacy of pre-operative ± post-operative therapies in patients with mCRC.…”

Section: Discussionsupporting

confidence: 67%

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer

et al. 2023

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Background Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. Materials and Methods Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. Results The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). Conclusion These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

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Section: Discussionsupporting

confidence: 67%

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer

et al. 2023

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“…In fact, the authors demonstrated that using bevacizumab increases the rates of metastasectomy. Moreover, real-life and interventional studies also suggested that patients who receive bevacizumab with chemotherapy prior to liver resection have improved OS, PFS and metastasectomy rates [ 24 – 27 ]. The favorable impact of bevacizumab in this setting was also found to be associated with reduced sinusoidal obstruction syndrome and hepatic fibrosis [ 28 ] as well as enhanced volumetric restoration [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab in metastatic colorectal cancer in a real-life setting – toxicity profile, survival outcomes, and impact of tumor sidedness

Chibani¹,

Bairi²,

Jarroudi³

et al. 2022

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Introduction Targeting angiogenesis in metastatic colorectal cancer (mCRC) using bevacizumab is a standard of care. The addition of this targeted biological agent to first-line infusional fluoropyrimidine-based chemotherapy was associated with superior overall survival (OS) in several randomized and controlled studies for CRC patients in the metastatic setting. However, access to this therapy in countries with limited resources is challenging. In Morocco, bevacizumab was introduced for this indication after considerable efforts of the Ministry of Health and Lalla Salma Foundation to support cancer patients with a limited income. In this report, the real-world efficacy and safety of the combination of bevacizumab with chemotherapy in mCRC are reported based on a retrospective cohort in Eastern Morocco. Material and methods The archives of the medical records of 98 mCRC patients treated with first-line bevacizumab at the Hassan II Regional Cancer Center (Oujda, Morocco) were sampled from 1 st January 2014 to 31 st December 2019 and analyzed using descriptive statistics, Kaplan-Meier estimation, and a multivariable Cox regression model for a time-to-event study. Results The toxicity profile was dominated by grade I–II proteinuria (10%), bleeding events (10%), thromboembolic events (9%), grade I–III hypertension (3%), and other rare events such as delayed healing of the stoma, scar dehiscence, intestinal perforation, and heart failure deterioration. In terms of survival, median OS and progression-free survival in the whole cohort were 22 and 13 months respectively. Patients who benefited from a metastasectomy after bevacizumab treatment had 31 months of median OS as compared to 14 months in the matched cohort with non-resectable liver metastasis. Notably, we demonstrated that tumor sidedness is a predictive factor of OS [hazard ratio (HR) = 2.452; 95% CI: 1.434–4.191, p = 0.001]. Moreover, the median OS for patients who received between 10 and 20 or more than 20 bevacizumab administrations was 24 and 33 months respectively as compared to those who received less than 10 cures (17 months) (log rank p < 0.0001). These markedly improved outcomes were also confirmed in multivariate Cox regression. A highly significant association of bevacizumab use and OS was found after adjusting for covariates (HR = 0.518, 95% CI: 0.374–0.717; p < 0.0001). Conclusions The current study confirmed the important place of this therapeutic strategy in mCRC. Additional studies with prospective enrollment are awaited to validate these findings.

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“…While perioperative administration of bevacizumab and chemotherapy for patients with liver metastatic CRC might be tolerable and helpful in prolonging survival, several phase II trials showed that recurrence was unavoidable, which lacks further validation. [457][458][459][460] As for locally advanced rectal cancer, abundant phase II studies have been conducted for the neoadjuvant use of anti-EGFR or anti-VEGF therapy, with pooled estimated pCR values of 27% and 14% being reported for bevacizumab-and cetuximab-relevant regimens, respectively, via a meta-analysis of 32 previous studies. 448 Although newer trials echoed the results from metaanalysis, 461 to elucidate whether the targeted agents are truly effective in the neoadjuvant setting still requires larger population-based head-to-head, time-to-event data.…”

Section: Immune Checkpoint Inhibitor Therapymentioning

confidence: 99%

Comprehensive review of targeted therapy for colorectal cancer

Xie

Chen

Fang

2020

Sig Transduct Target Ther

958

821

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Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world and was responsible for nearly 881,000 cancer-related deaths in 2018. Surgery and chemotherapy have long been the first choices for cancer patients. However, the prognosis of CRC has never been satisfying, especially for patients with metastatic lesions. Targeted therapy is a new optional approach that has successfully prolonged overall survival for CRC patients. Following successes with the anti-EGFR (epidermal growth factor receptor) agent cetuximab and the anti-angiogenesis agent bevacizumab, new agents blocking different critical pathways as well as immune checkpoints are emerging at an unprecedented rate. Guidelines worldwide are currently updating the recommended targeted drugs on the basis of the increasing number of high-quality clinical trials. This review provides an overview of existing CRC-targeted agents and their underlying mechanisms, as well as a discussion of their limitations and future trends.

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Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases

Cited by 7 publications

References 39 publications

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer

Bevacizumab in metastatic colorectal cancer in a real-life setting – toxicity profile, survival outcomes, and impact of tumor sidedness

Comprehensive review of targeted therapy for colorectal cancer

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