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. 2019 Sep:47:78-88.
doi: 10.1016/j.ebiom.2019.08.006. Epub 2019 Aug 19.

Role of immune checkpoint inhibitor-based therapies for metastatic renal cell carcinoma in the first-line setting: A Bayesian network analysis

Junpeng Wang  1 , Xin Li  2 , Xiaoqiang Wu  1 , Zhiwei Wang  1 , Chan Zhang  1 , Guanghui Cao  1 , Xiaofan Zhang  2 , Feng Peng  2 , Tianzhong Yan  3
Affiliations

Role of immune checkpoint inhibitor-based therapies for metastatic renal cell carcinoma in the first-line setting: A Bayesian network analysis

Junpeng Wang et al. EBioMedicine. 2019 Sep.

Abstract

Background: Several novel immune checkpoint inhibitor (ICI)-based treatments exhibited promising survival benefits for metastatic renal cell carcinoma (mRCC), yet there is no current guidance regarding the optimum first-line regimen. We performed this network analysis to compare the efficacy and safety of all available treatments for mRCC.

Methods: A systematic search of literature was conducted up to April 30, 2019, and the analysis was done on a Bayesian fixed-effect model.

Findings: Twenty-five randomized clinical trials (RCTs) involving 13,010 patients were included in this study. The results showed that for overall survival, pembrolizumab plus axitinib (hazard ratio [HR]: 0.53; 95% credible interval [CrI]: 0.38-0.73) and nivolumab plus ipilimumab (HR: 0.63; 95% CrI: 0.50-0.79) were significantly more effective than sunitinib, and pembrolizumab plus axitinib was probably (68%) to be the best choice. For progression-free survival, cabozantinib (HR: 0.66; 95% CrI: 0.46-0.94), pembrolizumab plus axitinib (HR: 0.69; 95% CrI: 0.57-0.84), avelumab plus axitinib (HR: 0.69; 95% CrI: 0.56-0.85), nivolumab plus ipilimumab (HR: 0.82; 95% CrI: 0.68-0.99), and atezolizumab plus bevacizumab (HR: 0.86; 95% CrI: 0.74-0.99) were statistically superior to sunitinib, and cabozantinib was likely (43%) to be the preferred options. Nivolumab plus ipilimumab (OR: 0.50; 95% CrI: 0.28-0.84), and atezolizumab plus bevacizumab (OR: 0.56; 95% CrI: 0.36-0.83) were associated with significantly lower rate of high-grade adverse events than sunitinib.

Interpretation: Our findings demonstrate that pembrolizumab plus axitinib might be the best treatment for mRCC, while nivolumab plus ipilimumab has the most favorable balance between efficacy and acceptability, and may provide new guidance to make treatment decisions. FUND: This research was supported by the Henan Provincial Scientific and Technological Research Project (Grant No. 192102310036).

Keywords: Efficacy; First-line systemic therapies; Immune checkpoint inhibitor; Renal cell carcinoma; Safety.

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Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Literature search and selection.
Fig. 2
Fig. 2
Network of the comparisons for the Bayesian network meta-analysis. Network plot for (A) OS, (B) PFS and (C) high-grade AEs. The size of every treatment node corresponds to the number of randomly assigned patients. The width of the lines is proportional to the number of trials. SUN = sunitinib. CAB = cabozantinib. NIV_IPI = nivolumab plus ipilimumab. PEM_AXI = pembrolizumab plus axitinib. AVE_AXI = avelumab plus axitinib. ATE_BEV = atezolizumab plus bevacizumab. EVE_BEV = everolimus plus bevacizumab. TEM_BEV = temsirolimus plus bevacizumab. TEM_IFN = temsirolimus plus interferon-α. PAZ_EVE = pazopanib plus everolimus. BEV_IFN = bevacizumab plus interferon-α. SOR_TRE = sorafenib plus trebananib. SOR_IL-2 = sorafenib plus interleukin-2. SOR_IFN = sorafenib plus interferon-α. PAZ = pazopanib. ATE = atezolizumab. TEM = temsirolimus. AXI = axitinib. TIV = tivozanib. NIN = nintedanib. EVE = everolimus. SOR = sorafenib. IFN = interferon-α.
Fig. 3
Fig. 3
Pooled hazard ratios for overall survival. (A) Forest plot, with sunitinib as the comparator; (B) Forest plot, with pembrolizumab plus axitinib as the comparator. HR = hazard ratio. CrI = credible interval. Numbers in parentheses indicate 95% credible intervals. SUN = sunitinib. CAB = cabozantinib. NIV_IPI = nivolumab plus ipilimumab. PEM_AXI = pembrolizumab plus axitinib. AVE_AXI = avelumab plus axitinib. ATE_BEV = atezolizumab plus bevacizumab. EVE_BEV = everolimus plus bevacizumab. TEM_BEV = temsirolimus plus bevacizumab. TEM_IFN = temsirolimus plus interferon-α. PAZ_EVE = pazopanib plus everolimus. BEV_IFN = bevacizumab plus interferon-α. PAZ = pazopanib. TEM = temsirolimus. NIN = nintedanib. IFN = interferon-α.
Fig. 4
Fig. 4
Pooled hazard ratios for progression-free survival. (A) Forest plot, with sunitinib as the comparator; (B) Forest plot, with pembrolizumab plus axitinib as the comparator. HR = hazard ratio. CrI = credible interval. Numbers in parentheses indicate 95% credible intervals. SUN = sunitinib. CAB = cabozantinib. NIV_IPI = nivolumab plus ipilimumab. PEM_AXI = pembrolizumab plus axitinib. AVE_AXI = avelumab plus axitinib. ATE_BEV = atezolizumab plus bevacizumab. EVE_BEV = everolimus plus bevacizumab. TEM_BEV = temsirolimus plus bevacizumab. TEM_IFN = temsirolimus plus interferon-α.PAZ_EVE = pazopanib plus everolimus. BEV_IFN = bevacizumab plus interferon-α. SOR_TRE = sorafenib plus trebananib. SOR_IL-2 = sorafenib plus interleukin-2. SOR_IFN = sorafenib plus interferon-α. PAZ = pazopanib. ATE = atezolizumab. TEM = temsirolimus. AXI = axitinib. TIV = tivozanib. NIN = nintedanib. EVE = everolimus. SOR = sorafenib. IFN = interferon-α.
Fig. 5
Fig. 5
Pooled odds ratios for high-grade adverse events. The column treatment is compared with the row treatment. ORs lower than 1 favor the column-defining treatment. Numbers in parentheses indicate 95% credible intervals. Significant results are underscored. SUN = sunitinib. CAB = cabozantinib. NIV_IPI = nivolumab plus ipilimumab. PEM_AXI = pembrolizumab plus axitinib. AVE_AXI = avelumab plus axitinib. ATE_BEV = atezolizumab plus bevacizumab. EVE_BEV = everolimus plus bevacizumab. TEM_BEV = temsirolimus plus bevacizumab. TEM_IFN = temsirolimus plus interferon-α. PAZ_EVE = pazopanib plus everolimus. BEV_IFN = bevacizumab plus interferon-α. SOR_TRE = sorafenib plus trebananib. SOR_IL-2 = sorafenib plus interleukin-2. PAZ = pazopanib. ATE = atezolizumab. TEM = temsirolimus. TIV = tivozanib. SOR = sorafenib. NIN = nintedanib. IFN = interferon-α.
Fig. 6
Fig. 6
Ranking of treatments in terms of overall survival. Rankograms were drawn according to distribution of the ranking probabilities. Ranking indicates the probability to be the best treatment, the second best, the third best, and so on in terms of overall survival, among 15 treatments. SUN = sunitinib. CAB = cabozantinib. NIV_IPI = nivolumab plus ipilimumab. PEM_AXI = pembrolizumab plus axitinib. AVE_AXI = avelumab plus axitinib. ATE_BEV = atezolizumab plus bevacizumab. EVE_BEV = everolimus plus bevacizumab. TEM_BEV = temsirolimus plus bevacizumab. TEM_IFN = temsirolimus plus interferon-α. PAZ_EVE = pazopanib plus everolimus. BEV_IFN = bevacizumab plus interferon-α. PAZ = pazopanib. TEM = temsirolimus. NIN = nintedanib. IFN = interferon-α.
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