International Journal of Clinical Case Reports 2024, Vol.14, No.4, 189-201 http://medscipublisher.com/index.php/ijccr 195 Figure 1 Combination therapy of anti-PD-L1 and 5-FU in RCC subcutaneous mouse model. Mice were randomly allocated to different groups to accept different treatments: IgG, anti-PD-L1 Abs, 5-FU, and 5-FU and anti-PD-L1 Abs (Adopted from Cui et al., 2017) Image caption: (A) The survival curves indicated that the mice treated with 5-FU and anti-PD-L1 Abs had longer survival times compared to the mice receiving 5-FU or anti-PD-L1 Abs single treatment. (B) The tumor volume increase of mice receiving 5-FU and anti-PD-L1 combination treatment was the slowest among all the treatment groups (Adopted from Cui et al., 2017). 4.4 Clinical efficacy evaluation: overall survival, progression-free survival, objective response rate The efficacy of immune checkpoint blockade therapies in renal cell carcinoma is typically evaluated using clinical endpoints such as overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). In clinical trials, OS represents the gold standard for determining the effectiveness of a treatment. For example, in the CheckMate 214 trial, the combination of nivolumab and ipilimumab demonstrated a significant improvement in OS compared to sunitinib, with a median survival benefit extending beyond 30 months in intermediate- and poor-risk patients (Bedke et al., 2020). Progression-free survival (PFS), which measures the time during and after treatment that a patient lives without disease progression, is another key endpoint. In the KEYNOTE-426 trial, pembrolizumab and axitinib significantly prolonged PFS compared to sunitinib in treatment-naive patients, with benefits observed across all subgroups (Massari et al., 2021). Objective response rate (ORR) refers to the proportion of patients whose tumors shrink or disappear following treatment. Combination therapies involving immune checkpoint inhibitors have been shown to improve ORRs in patients with mRCC. For instance, the ORR in patients receiving the combination of nivolumab and cabozantinib was significantly higher than those receiving monotherapy, with more patients achieving partial or complete responses (Flippot et al., 2018). 5 Safety and Adverse Effects Immune checkpoint blockade (ICB) therapies, such as those targeting PD-1, PD-L1, and CTLA-4, have shown remarkable efficacy in treating renal cell carcinoma (RCC). However, these therapies are also associated with a range of immune-related adverse events (irAEs). 5.1 Common adverse effects and their management ICB therapies can induce irAEs, which result from the immune system becoming overactive and attacking healthy tissues. These irAEs can affect various organ systems, including the skin, gastrointestinal tract, liver, endocrine glands, and kidneys. Common irAEs include colitis, hepatitis, pneumonitis, nephritis, hypothyroidism, and rash. Severe cases of irAEs may lead to life-threatening complications, such as autoimmune encephalitis or severe interstitial nephritis (Murakami et al., 2016; Mysler et al., 2023).
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