The Predictive Role of Primary Tumour Sidedness in Metastatic Colorectal Cancer Treated With Targeted Agents

Fiala, Ondřej; Ostasov, Pavel; Hošek, Petr; Šorejs, Ondřej; Liška, Václav; Büchler, Tomáš; Poprach, Alexandr; Kučera, Radek; Topolčan, Ondřej; Šustr, Jan; Sedivcova, Monika; Fínek, Jindřich

doi:10.21873/anticanres.13761

Cited by 10 publications

(5 citation statements)

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“…Primary tumor sidedness is a prognostic factor in patients with WT RAS mCRC, and right-sided primary tumors was associated with poor prognosis. A cohort study with 178 patients with mCRC showed similar results in that superior OS and PFS were observed when anti-EGFR was added to therapy for patients with for left-sided primary tumors (20).…”

Section: Discussionmentioning

confidence: 80%

Efficacy of First-line Therapy With Anti-EGFR Versus Anti-VEGF Therapy for WT RAS Metastatic Colorectal Cancer: Real-world Experience from a Single Institute

Chiang,

Huang,

Chiang

et al. 2024

Preprint

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Background/Aim: Top prospective clinical trials comparing anti-epidermal growth factor receptor (EGFR) therapy and anti-vascular endothelial growth factor (VEGF) therapy plus chemotherapy for wild-type Ras proto-oncogene, GTPase (WT RAS) metastatic colorectal cancer (mCRC) have yielded different outcomes, and real-world data are lacking. This study established real-world experiences and identified challenges in treating patients with mCRC. Patients and Methods: This retrospective study identified first-line regimens for patients with mCRC on anti-EGFR or anti-VEGF therapy plus chemotherapy. The effects on overall survival (OS) were estimated; secondary endpoints were progression-free survival (PFS). OS in the two groups was compared on the basis of sex, age, primary tumor site, oxaliplatin-based chemotherapy, and number of organs with metastases through Cox multivariate regression analysis. Results: A total of 129 patients diagnosed with WT RAS mCRC from June 1, 2018, to December 31, 2021, were included. The median OS was 33.3 months for the anti-EGFR group (n = 78) and 26.1 months for the anti-VEGF group (n = 51; 95% confidence interval = 1.008–2.550; p = 0.044). PFS was 17.6 and 12 months, respectively (95% confidence interval = 0.9-1.963; p = 0.15). Multivariate Cox regression models revealed good OS for patients with WT RAS and left-sided primary tumor. The liver-only metastasis conversion rate after systemic chemotherapy was higher in the anti-EGFR group. Conclusion: High survival rates can be achieved when anti-EGFR is used in patients with WT RAS mCRC. Surgery still plays an important role in patients with mCRC and on systemic treatments.

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Section: Discussionmentioning

confidence: 80%

Efficacy of First-line Therapy With Anti-EGFR Versus Anti-VEGF Therapy for WT RAS Metastatic Colorectal Cancer: Real-world Experience from a Single Institute

Chiang,

Huang,

Chiang

et al. 2024

Preprint

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“…The existing pharmacological treatment of UC is accompanied by a series of problems and a high incidence of adverse effects[ 31 , 32 ]. Moreover, multiple morbidities tend to occur during treatment, and the long-term use of drugs such as sulfonamides and glucocorticosteroids can lead to a gradual decrease in medication adherence and a substantial economic burden for patients[ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Unraveling the mechanism of malancao in treating ulcerative colitis: A multi-omics approach

Huang,

Wu,

Huang

et al. 2024

World J Clin Cases

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BACKGROUND Malancao (MLC) is a traditional Chinese medicine with a long history of utilization in treating ulcerative colitis (UC). Nevertheless, the precise molecular mechanisms underlying its efficacy remain elusive. This study leveraged ultra-high-performance liquid chromatography coupled with exactive mass spectrometry (UHPLC-QE-MS), network pharmacology, molecular docking (MD), and gene microarray analysis to discern the bioactive constituents and the potential mechanism of action of MLC in UC management. AIM To determine the ingredients related to MLC for treatment of UC using multiple databases to obtain potential targets for fishing. METHODS This research employs UHPLC-QE-MS for the identification of bioactive compounds present in MLC plant samples. Furthermore, the study integrates the identified MLC compound-related targets with publicly available databases to elucidate common drug disease targets. Additionally, the R programming language is utilized to predict the central targets and molecular pathways that MLC may impact in the treatment of UC. Finally, MD are conducted using AutoDock Vina software to assess the affinity of bioactive components to the main targets and confirm their therapeutic potential. RESULTS Firstly, through a comprehensive analysis of UHPLC-QE-MS data and public database resources, we identified 146 drug-disease cross targets related to 11 bioactive components. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted that common disease drug targets are primarily involved in oxidative stress management, lipid metabolism, atherosclerosis, and other processes. They also affect AGE-RAGE and apoptosis signaling pathways. Secondly, by analyzing the differences in diseases, we identified key research targets. These core targets are related to 11 active substances, including active ingredients such as quercetin and luteolin. Finally, MD analysis revealed the stability of compound-protein binding, particularly between JUN-Luteolin, JUN-Quercetin, HSP90AA1-Wogonin, and HSP90AA1-Rhein. Therefore, this suggests that MLC may help alleviate intestinal inflammation in UC, restore abnormal lipid accumulation, and regulate the expression levels of core proteins in the intestine. CONCLUSION The utilization of MLC has demonstrated notable therapeutic efficacy in the management of UC by means of the compound target interaction pathway. The amalgamation of botanical resources, metabolomics, natural products, MD, and gene chip technology presents a propitious methodology for investigating therapeutic targets of herbal medicines and discerning novel bioactive constituents.

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“…Furthermore, the results of this study are in agreement with the observations of several other recent retrospective analyses. 13,14,21,22 In light of mounting evidence for the inferiority of first-line bevacizumab in left-sided RAS/RAF WT mCRC, it is unclear why uptake of anti-EGFR agents remains low in the United States. Route of administration and dosing schedule are similar, and compared with bevacizumab, which is associated with serious adverse events such hypertension, gastrointestinal perforation, and thromboembolic events, one could argue that anti-EGFR agents are actually less toxic.…”

Section: Discussionmentioning

confidence: 99%

Treatment Trends and Clinical Outcomes of Left-Sided RAS/RAF Wild-Type Metastatic Colorectal Cancer in the United States

Nevala-Plagemann

Iyengar²,

Trunk³

et al. 2022

Journal of the National Comprehensive Cancer Network

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Background: Post hoc analysis of the CALGB/SWOG 80405 trial suggests that anti-EGFR therapy may be superior to bevacizumab when added to first-line chemotherapy in patients with metastatic colorectal cancer (mCRC) who have left-sided primary tumors. We evaluated trends in use of anti-EGFR agents in patients with left-sided RAS/RAF wild-type (WT) mCRC and compared clinical outcomes among the most commonly used treatment strategies. Methods: A nationwide electronic health record (EHR)–derived deidentified database was reviewed for patients with left-sided RAS/RAF WT mCRC. Treatment trends over time were assessed by fitting a linear model to the percentage of patients receiving anti-EGFR therapy. A propensity score weighted Cox model was used to compare overall survival (OS) stratified by first-line targeted therapy received. Results: A total of 1,607 patients with left-sided RAS/RAF WT mCRC received standard first-line chemotherapy. Of these, 965 (60%) received bevacizumab and 186 (12%) received an anti-EGFR agent. The percentage of patients receiving an anti-EGFR increased from 9% in 2013 to 16% in 2018. Median OS for patients treated with chemotherapy alone was 27.3 months (95% CI, 24.8–32.3), 27.5 months with bevacizumab (95% CI, 25.8–28.9; hazard ratio [HR], 0.88; P=.33), and 42.9 months with an anti-EGFR agent (95% CI, 36.0 to not reached; HR, 0.52; P=.005). Conclusions: This analysis suggests that chemotherapy with bevacizumab remained the most widely used first-line treatment strategy for patients with left-sided RAS/RAF WT mCRC in the United States in 2018. Despite this preference, treatment with an anti-EGFR agent was associated with improved OS.

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The Predictive Role of Primary Tumour Sidedness in Metastatic Colorectal Cancer Treated With Targeted Agents

Cited by 10 publications

References 0 publications

Efficacy of First-line Therapy With Anti-EGFR Versus Anti-VEGF Therapy for WT RAS Metastatic Colorectal Cancer: Real-world Experience from a Single Institute

Efficacy of First-line Therapy With Anti-EGFR Versus Anti-VEGF Therapy for WT RAS Metastatic Colorectal Cancer: Real-world Experience from a Single Institute

Unraveling the mechanism of malancao in treating ulcerative colitis: A multi-omics approach

Treatment Trends and Clinical Outcomes of Left-Sided RAS/RAF Wild-Type Metastatic Colorectal Cancer in the United States

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