Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 126-135 http://medscipublisher.com/index.php/cge 129 of time, and have more patients whose tumors shrink. For instance, a multicenter study found that with bevacizumab treatment, the proportion of patients with tumor shrinkage was 34.7%, and the average survival time of the patients was 18 months. When treated with afriximab, these two figures were 21.5% and 12.5 months respectively. Especially for those patients with normal RAS/BRAF genes, bevacizumab had a better effect (Lo Prinzi et al., 2025). In addition, when irinotecan, TAS-102 and bevacizumab were used together, the effect was also good in the second treatment. 83.3% of the patients had their conditions controlled, and the average time for the condition not to deteriorate was 6.9 months (Zhang et al., 2024; Zhang et al., 2025). During the third treatment, TAS-102 combined with bevacizumab was also helpful for patients who had a poor response to the previous treatment. Studies show that the average time for patients' conditions not to deteriorate is 4.5-4.6 months, and the average survival time is 9.3-10.5 months. The adverse reactions after medication can be controlled, and no patients die due to medication. Therefore, this treatment method can be used as an option for later treatment (Ishida et al., 2020; Yoshida et al., 2022). 4.2 Comparative studies with other targeted agents Comparative studies have found that during the second treatment, using bevacizumab in combination with other drugs may be more effective than using other similar anti-cancer drugs. In direct comparison, bevacizumab is superior to afericept in terms of allowing patients to live longer, maintaining a longer period of non-deterioration of the disease, and having a higher proportion of tumor shrinkage, especially for patients with normal RAS/BRAF genes (average survival time: 20.2 months vs 10.6 months). Time without deterioration of the condition: 8.4 months vs 3.7 months; Tumor shrinkage ratio: 48.6% vs. 15.0% (Lo Prinzi et al., 2025). Although there are similar anti-cancer drugs such as ramucirumab and afliberept, there are still not many studies directly comparing their effects with bevacizumab. However, the available evidence now indicates that in the subsequent treatments, bevacizumab combined with other drugs is better, especially for patients with certain specific genetic types (Yoshino et al., 2023; Lo Prinzi et al., 2025). 4.3 Treatment responses in special patient populations Bevacizumab combined with other drugs is also effective in treating some special patients, such as those with RAS gene mutations and those whose conditions worsen after the first treatment. For patients with metastatic colorectal cancer with RAS gene mutations, after the second treatment with bevacizumab, the average time for the disease not to deteriorate was 171 days. 75.6% of the patients had their disease controlled, and no new safety issues emerged (Luo et al., 2025). For those patients whose previous treatment was ineffective or whose condition relapsed, after the first treatment had a poor effect, continuing to use bevacizumab or starting anew would improve the treatment effect. The average time for the condition not to deteriorate could reach 6.8 months, and it might also enable the patients to live longer. Therefore, when treating these more difficult patients, Bevacizumab can also be used (Amoroso et al., 2015). 5 Common Adverse Effects and Management 5.1 Incidence of key adverse effects The combination of bevacizumab and other drugs in the treatment of advanced colorectal cancer may cause some common side effects, the most prominent of which are elevated blood pressure, protein in urine and bleeding problems. Approximately 5% to 18% of patients will develop relatively severe hypertension (grade 3 hypertension), while less severe proteinuria (grade 1 or 2) is also very common. The probability of relatively severe bleeding conditions (grade 3 or 4) has also increased slightly, at around 1.2%~4.6%. Especially for patients who have undergone surgery during the treatment period, the wound may not heal easily (Saini and Hurwitz, 2006; Wichelmann et al., 2021; Chitkara et al., 2023). Some people have infections or problems with the intestines and stomach, such as leakage at the intestinal junction or gastric mucosal ulcers. Moreover, when bevacizumab is used in combination with chemotherapy,
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