Findings

What do systematic reviews say?

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Evidence found and GRADE certainty

34 questions · 34 findings · 8 reviews · Headline outcomes only

No studies found 2 · 5.9%GRADE not reported 1 · 2.9%Very low 4 · 11.8%Low 15 · 44.1%Moderate 10 · 29.4%High 2 · 5.9%

Immune checkpoint inhibitors vs any first‐line chemotherapy

Adverse events grade 3 to 5 Range of · participants with advanced or metastatic muscle invasive bladder cancer

Immune checkpoint inhibitors probably leads to lower adverse events grade 3 to 5 Range of compared with any first‐line chemotherapy (moderate certainty).

1 finding from 1 review

Sorafenib vs pazopanib (targeted agent versus targeted agent)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (any cell type)

It is very uncertain whether sorafenib changes serious adverse events (Grade 3 or 4) compared with pazopanib (targeted agent versus targeted agent) (very low certainty).

1 finding from 1 review

Sunitinib vs avelumab + axitinib (targeted agent versus immunotherapy + targeted agent)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (clear cell type)

Sunitinib showed no clear difference in serious adverse events (Grade 3 or 4) compared with avelumab + axitinib (targeted agent versus immunotherapy + targeted… (low certainty).

1 finding from 1 review

Sunitinib vs pembrolizumab + axitinib (targeted agent versus immunotherapy + targeted agent)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (clear cell type)

Sunitinib showed no clear difference in serious adverse events (Grade 3 or 4) compared with pembrolizumab + axitinib (targeted agent versus immunotherapy +… (low certainty).

1 finding from 1 review

Sorafenib vs sunitinib (targeted agent versus targeted agent)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (any cell type)

It is very uncertain whether sorafenib changes serious adverse events (Grade 3 or 4) compared with sunitinib (targeted agent versus targeted agent) (very low certainty).

1 finding from 1 review

Sunitinib vs atezolizumab + bevacizumab (targeted agent versus immunotherapy + targeted agent)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (clear cell type)

It is very uncertain whether sunitinib changes serious adverse events (Grade 3 or 4) compared with atezolizumab + bevacizumab (targeted agent versus immunotherapy +… (very low certainty).

1 finding from 1 review

Sunitinib vs IMA901 + sunitinib (targeted agent versus tumour vaccine + targeted agent)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (clear cell type)

Sunitinib may leads to lower serious adverse events (Grade 3 or 4) compared with IMA901 + sunitinib (targeted agent versus tumour vaccine + targeted… (low certainty).

1 finding from 1 review

Sunitinib vs atezolizumab (targeted therapy versus immunotherapy)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (clear cell type)

Sunitinib probably leads to higher serious adverse events (Grade 3 or 4) compared with atezolizumab (targeted therapy versus immunotherapy) (moderate certainty).

1 finding from 1 review

Bevacizumab + IFN vs IFN (+ placebo) (targeted agent + classic immunotherapy versus classic immunotherapy)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (clear cell type)

Bevacizumab + IFN probably leads to higher serious adverse events (Grade 3 or 4) compared with IFN (+ placebo) (targeted agent + classic immunotherapy versus… (moderate certainty).

1 finding from 1 review

Temsirolimus + IFN‐α vs IFN (+ placebo) (targeted agent + classic immunotherapy versus classic immunotherapy)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (any cell type)

Temsirolimus + IFN‐α may leads to higher serious adverse events (Grade 3 or 4) compared with IFN‐α (targeted agent + classic immunotherapy versus classic… (low certainty).

1 finding from 1 review

Temsirolimus + bevacizumab vs bevacizumab + IFN‐α (targeted agent + targeted agent versus targeted agent + classic immunotherapy)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (any cell type)

Temsirolimus + bevacizumab showed no clear difference in serious adverse events (Grade 3 or 4) compared with bevacizumab + IFN‐α (targeted agent + targeted agent versus targeted… (low certainty).

1 finding from 1 review

Everolimus + bevacizumab vs bevacizumab + IFN‐α (targeted agent + targeted agent versus targeted agent + classic immunotherapy)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (any cell type)

Everolimus + bevacizumab showed no clear difference in serious adverse events (Grade 3 or 4) compared with IFN α‐2a + bevacizumab (targeted agent + targeted agent versus… (low certainty).

1 finding from 1 review

Sunitinib vs adjuvant immunotherapy (combined ipilimumab and nivolumab)

Serious adverse events (Grade 3 or 4) · Treatment‐naïve metastatic renal cell carcinoma (clear cell type); IMDC intermediate, poor risk patients only.

Sunitinib probably leads to higher serious adverse events (Grade 3 or 4) compared with nivolumab + ipilimumab (targeted agent versus combinations of… (moderate certainty).

1 finding from 1 review