Cochrane · systematic review · CD012796
Targeted therapy for metastatic renal cell carcinoma
Hofmann, F, Hwang, EC, Lam, TBL, et al. · Cochrane Database of Systematic Reviews · 2020 · Cochrane Library
UrologyAMSTAR 2: not assessed
SoF tableOnly the outcomes this review put in its Summary of Findings table are listed (the Cochrane Handbook caps them at about seven per comparison). Its other analyses are not shown here.
Questions
72
current version
GRADE rated
65
No studies
7
Included studies
NR
No studies 7 · 9.7%Ungraded 0 · 0%Very low 10 · 13.9%Low 35 · 48.6%Moderate 16 · 22.2%High 4 · 5.6%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Questions and results
Sorafenib compared to sunitinib (targeted agent versus targeted agent)
Population: Treatment‐naïve metastatic renal cell carcinoma (any cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 10 months) Sorafenib vs sunitinib (targeted agent versus targeted agent) | HR 1.19 [0.92, 1.53] | 1 study · 365 participants | Low Downgraded: risk of bias |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Sorafenib vs sunitinib (targeted agent versus targeted agent) | HR 0.99 [0.74, 1.33] | 1 study · 365 participants | Very low Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4) Sorafenib vs sunitinib (targeted agent versus targeted agent) | RR 0.99 [0.85, 1.14] | 1 study · 353 participants | Very low Downgraded: risk of bias |
Health‐related quality of life5 Sorafenib vs sunitinib (targeted agent versus targeted agent) | no estimate extracted | NR | No studies |
Pazopanib compared to sunitinib (targeted agent versus targeted agent)
Population: Treatment‐naïve metastatic renal cell carcinoma (clear cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Pazopanib vs sunitinib (targeted agent versus targeted agent) | HR 1.05 [0.9, 1.23] | 1 study · 1110 participants | Low Downgraded: risk of bias |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Pazopanib vs sunitinib (targeted agent versus targeted agent) | HR 0.92 [0.8, 1.06] | 1 study · 1110 participants | Low Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4) Pazopanib vs sunitinib (targeted agent versus targeted agent) | RR 1.01 [0.94, 1.09] | 1 study · 1102 participants | Low Downgraded: risk of bias |
Health‐related quality of life (mean change value) Pazopanib vs sunitinib (targeted agent versus targeted agent) | no estimate extracted | 1 study · 467 participants | Low Downgraded: risk of bias, imprecision |
Tivozanib compared to sorafenib (targeted agent versus targeted agent)
Population: Treatment‐naïve metastatic renal cell carcinoma (clear cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Tivozanib vs sorafenib (targeted agent versus targeted agent) | HR 0.79 [0.64, 0.99] | 1 study · 517 participants | Low Downgraded: imprecision |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Tivozanib vs sorafenib (targeted agent versus targeted agent) | HR 1.25 [0.95, 1.64] | 1 study · 517 participants | Low Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4) Tivozanib vs sorafenib (targeted agent versus targeted agent) | RR 0.85 [0.74, 0.97] | 1 study · 516 participants | Low Downgraded: imprecision |
Health‐related quality of life Tivozanib vs sorafenib (targeted agent versus targeted agent) | no estimate extracted | 1 study · 506 participants | Low Downgraded: risk of bias, imprecision |
Sorafenib compared to pazopanib (targeted agent versus targeted agent)
Population: Treatment‐naïve metastatic renal cell carcinoma (any cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Sorafenib vs pazopanib (targeted agent versus targeted agent) | HR 1.92 [1.74, 2.11] | 1 study · 377 participants | Moderate Downgraded: risk of bias |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Sorafenib vs pazopanib (targeted agent versus targeted agent) | HR 1.22 [0.91, 1.64] | 1 study · 377 participants | Low Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4) Sorafenib vs pazopanib (targeted agent versus targeted agent) | RR 0.92 [0.78, 1.09] | 1 study · 366 participants | Very low Downgraded: risk of bias |
Health‐related quality of life(mean change value) Sorafenib vs pazopanib (targeted agent versus targeted agent) | no estimate extracted | 1 study · 267 participants | Low Downgraded: risk of bias, imprecision |
Sunitinib compared to everolimus (targeted agent versus targeted agent)
Population: Treatment‐naïve metastatic renal cell carcinoma (any cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Sunitinib vs everolimus (targeted agent versus targeted agent) | HR 0.71 [0.59, 0.87] | 1 study · 471 participants | Moderate Downgraded: risk of bias |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Sunitinib vs everolimus (targeted agent versus targeted agent) | HR 0.9 [0.72, 1.11] | 1 study · 471 participants | Low Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4) Sunitinib vs everolimus (targeted agent versus targeted agent) | RR 1.34 [1.14, 1.59] | 1 study · 469 participants | Moderate Downgraded: risk of bias |
Health‐related quality of life Sunitinib vs everolimus (targeted agent versus targeted agent) | no estimate extracted | 1 study · 288 participants | Low Downgraded: risk of bias |
Sunitinib compared to avelumab + axitinib (targeted agent versus immunotherapy + targeted agent)
Population: Treatment‐naïve metastatic renal cell carcinoma (clear cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival(absolute effect size estimates based on survival rate at 12 months) Sunitinib vs avelumab + axitinib (targeted agent versus immunotherapy + targeted agent) | HR 1.45 [1.17, 1.8] | 1 study · 886 participants | Moderate Downgraded: risk of bias |
Overall survival (absolute effect size estimates based on survival rate at 12 months) Sunitinib vs avelumab + axitinib (targeted agent versus immunotherapy + targeted agent) | HR 1.28 [0.92, 1.79] | 1 study · 886 participants | Low Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4) Sunitinib vs avelumab + axitinib (targeted agent versus immunotherapy + targeted agent) | RR 1.01 [0.93, 1.1] | 1 study · 873 participants | Low Downgraded: risk of bias |
Health‐related quality of life4 Sunitinib vs avelumab + axitinib (targeted agent versus immunotherapy + targeted agent) | no estimate extracted | NR | No studies |
Sunitinib compared to pembrolizumab + axitinib (targeted agent versus immunotherapy + targeted agent)
Population: Treatment‐naïve metastatic renal cell carcinoma (clear cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival(absolute effect size estimates based on survival rate at 12 months) Sunitinib vs pembrolizumab + axitinib (targeted agent versus immunotherapy + targeted agent) | HR 1.45 [1.19, 1.76] | 1 study · 861 participants | Moderate Downgraded: risk of bias |
Overall survival (absolute effect size estimates based on survival rate at 12 months) Sunitinib vs pembrolizumab + axitinib (targeted agent versus immunotherapy + targeted agent) | HR 1.9 [1.36, 2.65] | 1 study · 861 participants | Moderate Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4) Sunitinib vs pembrolizumab + axitinib (targeted agent versus immunotherapy + targeted agent) | RR 0.9 [0.81, 1.02] | 1 study · 854 participants | Low Downgraded: risk of bias |
Health‐related quality of life4 Sunitinib vs pembrolizumab + axitinib (targeted agent versus immunotherapy + targeted agent) | no estimate extracted | NR | No studies |
Sunitinib compared to atezolizumab + bevacizumab (targeted agent versus immunotherapy + targeted agent)
Population: Treatment‐naïve metastatic renal cell carcinoma (clear cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival(absolute effect size estimates based on survival rate at 12 months) Sunitinib vs atezolizumab + bevacizumab (targeted agent versus immunotherapy + targeted agent) | HR 1.18 [1.02, 1.36] | 2 studies · 1117 participants | Low Downgraded: imprecision |
Overall survival(absolute effect size estimates based on survival rate at 24 months) Sunitinib vs atezolizumab + bevacizumab (targeted agent versus immunotherapy + targeted agent) | HR 0.99 [0.73, 1.33] | 2 studies · 1117 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Serious adverse events (Grade 3 or 4) Sunitinib vs atezolizumab + bevacizumab (targeted agent versus immunotherapy + targeted agent) | RR 1.22 [1, 1.49] | 2 studies · 1098 participants | Very low Downgraded: risk of bias, imprecision, inconsistency |
Health‐related quality of life Sunitinib vs atezolizumab + bevacizumab (targeted agent versus immunotherapy + targeted agent) | no estimate extracted | 2 studies · 691 participants | Low Downgraded: imprecision |
Sunitinib compared to IMA901 + sunitinib (targeted agent versus tumour vaccine + targeted agent)
Population: Treatment‐naïve metastatic renal cell carcinoma (clear cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Sunitinib vs IMA901 + sunitinib (targeted agent versus tumour vaccine + targeted agent) | HR 0.95 [0.7, 1.3] | 1 study · 339 participants | Very low Downgraded: imprecision |
Overall survival (absolute effect size estimates based on survival rate at 12 months) Sunitinib vs IMA901 + sunitinib (targeted agent versus tumour vaccine + targeted agent) | HR 0.75 [0.54, 1.04] | 1 study · 339 participants | Low Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4) Sunitinib vs IMA901 + sunitinib (targeted agent versus tumour vaccine + targeted agent) | RR 0.74 [0.59, 0.95] | 1 study · 334 participants | Low Downgraded: risk of bias, imprecision |
Health‐related quality of life6 Sunitinib vs IMA901 + sunitinib (targeted agent versus tumour vaccine + targeted agent) | no estimate extracted | NR | No studies |
Sunitinib compared to interferon‐α (IFN‐α) (targeted agent versus classic immunotherapy)
Population: Treatment‐naïve metastatic renal cell carcinoma (clear cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 6 months) Sunitinib vs interferon‐α (IFN‐α) (targeted agent versus classic immunotherapy) | HR 0.54 [0.45, 0.64] | 1 study · 750 participants | Moderate Downgraded: risk of bias |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Sunitinib vs interferon‐α (IFN‐α) (targeted agent versus classic immunotherapy) | HR 0.82 [0.67, 1] | 1 study · 750 participants | Low Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4)assessed as: CTCAE v3.0 Sunitinib vs interferon‐α (IFN‐α) (targeted agent versus classic immunotherapy) | RR 1.75 [1.43, 2.16] | 1 study · 735 participants | Moderate Downgraded: risk of bias |
Health‐related quality of life Sunitinib vs interferon‐α (IFN‐α) (targeted agent versus classic immunotherapy) | no estimate extracted | 1 study · 544 participants | Moderate Downgraded: risk of bias, imprecision |
Temsirolimus compared to IFN‐α (targeted agent versus classic immunotherapy)
Population: Treatment‐naïve metastatic renal cell carcinoma (any cell type [80% clear cell])
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Temsirolimus vs IFN‐α (targeted agent versus classic immunotherapy) | HR 0.74 [0.6, 0.91] | 1 study · 416 participants | Low Downgraded: imprecision |
Overall survival survival (absolute effect size estimates based on survival rate at 12 months ) Temsirolimus vs IFN‐α (targeted agent versus classic immunotherapy) | HR 0.78 [0.63, 0.97] | 1 study · 416 participants | Moderate Downgraded: imprecision |
Serious adverse events (Grade 3 or 4) Temsirolimus vs IFN‐α (targeted agent versus classic immunotherapy) | RR 0.86 [0.76, 0.97] | 1 study · 408 participants | Low Downgraded: imprecision |
Health‐related quality of life Temsirolimus vs IFN‐α (targeted agent versus classic immunotherapy) | no estimate extracted | 1 study · 401 participants | Low Downgraded: risk of bias, imprecision |
Sunitinib compared to atezolizumab (targeted therapy versus immunotherapy)
Population: Treatment‐naïve metastatic renal cell carcinoma (clear cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Sunitinib vs atezolizumab (targeted therapy versus immunotherapy) | HR 0.84 [0.58, 1.22] | 1 study · 204 participants | Very low Downgraded: imprecision |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Sunitinib vs atezolizumab (targeted therapy versus immunotherapy) | HR 0.94 [0.58, 1.54] | 1 study · 204 participants | Very low Downgraded: imprecision |
Serious adverse events (Grade 3 or 4) Sunitinib vs atezolizumab (targeted therapy versus immunotherapy) | RR 1.73 [1.32, 2.27] | 1 study · 203 participants | Moderate Downgraded: risk of bias, imprecision |
Health‐related quality of life Sunitinib vs atezolizumab (targeted therapy versus immunotherapy) | no estimate extracted | 1 study · 157 participants | Low Downgraded: risk of bias, imprecision |
Bevacizumab + IFN compared to IFN (+ placebo) (targeted agent + classic immunotherapy versus classic immunotherapy)
Population: Treatment‐naïve metastatic renal cell carcinoma (clear cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Bevacizumab + IFN vs IFN (+ placebo) (targeted agent + classic immunotherapy versus classic immunotherapy) | HR 0.68 [0.6, 0.77] | 2 studies · 1381 participants | Moderate Downgraded: risk of bias |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Bevacizumab + IFN vs IFN (+ placebo) (targeted agent + classic immunotherapy versus classic immunotherapy) | HR 0.88 [0.79, 0.99] | 2 studies · 1381 participants | Low Downgraded: risk of bias |
Serious adverse events (Grade 3 or 4) Bevacizumab + IFN vs IFN (+ placebo) (targeted agent + classic immunotherapy versus classic immunotherapy) | RR 1.31 [1.2, 1.42] | 2 studies · 1356 participants | Moderate Downgraded: risk of bias |
Health‐related quality of life3 Bevacizumab + IFN vs IFN (+ placebo) (targeted agent + classic immunotherapy versus classic immunotherapy) | no estimate extracted | NR | No studies |
Temsirolimus + IFN‐α compared to IFN‐α (targeted agent + classic immunotherapy versus classic immunotherapy)
Population: Treatment‐naïve metastatic renal cell carcinoma (any cell type [80% clear cell])
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Temsirolimus + IFN‐α vs IFN‐α (targeted agent + classic immunotherapy versus classic immunotherapy) | HR 0.76 [0.62, 0.93] | 1 study · 417 participants | Low Downgraded: imprecision |
Overall survival (absolute effect size estimates based on survival rate at 12 months) Temsirolimus + IFN‐α vs IFN‐α (targeted agent + classic immunotherapy versus classic immunotherapy) | HR 0.93 [0.75, 1.15] | 1 study · 417 participants | Low Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4) Temsirolimus + IFN‐α vs IFN‐α (targeted agent + classic immunotherapy versus classic immunotherapy) | RR 1.12 [1.02, 1.22] | 1 study · 408 participants | Low Downgraded: risk of bias, imprecision |
Health‐related quality of life Temsirolimus + IFN‐α vs IFN‐α (targeted agent + classic immunotherapy versus classic immunotherapy) | no estimate extracted | 1 study · 394 participants | Low Downgraded: risk of bias, imprecision |
Temsirolimus + bevacizumab compared to bevacizumab + IFN‐α (targeted agent + targeted agent versus targeted agent + classic immunotherapy)
Population: Treatment‐naïve metastatic renal cell carcinoma (any cell type [80% clear cell])
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Temsirolimus + bevacizumab vs bevacizumab + IFN‐α (targeted agent + targeted agent versus targeted agent + classic immunotherapy) | HR 1.1 [0.9, 1.34] | 1 study · 791 participants | Low Downgraded: imprecision |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Temsirolimus + bevacizumab vs bevacizumab + IFN‐α (targeted agent + targeted agent versus targeted agent + classic immunotherapy) | HR 1.08 [0.9, 1.3] | 1 study · 791 participants | Moderate Downgraded: imprecision |
Serious adverse events (Grade 3 or 4) Temsirolimus + bevacizumab vs bevacizumab + IFN‐α (targeted agent + targeted agent versus targeted agent + classic immunotherapy) | RR 1.05 [0.98, 1.13] | 1 study · 784 participants | Low Downgraded: imprecision |
Health‐related quality of life3 Temsirolimus + bevacizumab vs bevacizumab + IFN‐α (targeted agent + targeted agent versus targeted agent + classic immunotherapy) | no estimate extracted | NR | No studies |
Everolimus + bevacizumab compared to IFN α‐2a + bevacizumab (targeted agent + targeted agent versus targeted agent + classic immunotherapy)
Population: Treatment‐naïve metastatic renal cell carcinoma (any cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 18 months) Everolimus + bevacizumab vs IFN α‐2a + bevacizumab (targeted agent + targeted agent versus targeted agent + classic immunotherapy) | HR 0.91 [0.69, 1.2] | 1 study · 365 participants | Very low Downgraded: risk of bias |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Everolimus + bevacizumab vs IFN α‐2a + bevacizumab (targeted agent + targeted agent versus targeted agent + classic immunotherapy) | HR 1.01 [0.75, 1.36] | 1 study · 365 participants | Very low Downgraded: risk of bias, imprecision |
Serious adverse events (Grade 3 or 4) Everolimus + bevacizumab vs IFN α‐2a + bevacizumab (targeted agent + targeted agent versus targeted agent + classic immunotherapy) | RR 1.06 [0.95, 1.18] | 1 study · 361 participants | Low Downgraded: risk of bias |
Health‐related quality of life5 Everolimus + bevacizumab vs IFN α‐2a + bevacizumab (targeted agent + targeted agent versus targeted agent + classic immunotherapy) | no estimate extracted | NR | No studies |
Sunitinib compared to nivolumab + ipilimumab (targeted agent versus combinations of immunotherapy)
Population: Treatment‐naïve metastatic renal cell carcinoma (clear cell type); IMDC intermediate, poor risk patients only.
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 30 months) Sunitinib vs nivolumab + ipilimumab (targeted agent versus combinations of immunotherapy) | HR 1.3 [1.11, 1.52] | 1 study · 847 participants | Low Downgraded: imprecision |
Overall survival (absolute effect size estimates based on survival rate at 30 months) Sunitinib vs nivolumab + ipilimumab (targeted agent versus combinations of immunotherapy) | HR 1.52 [1.23, 1.89] | 1 study · 847 participants | High |
Serious adverse events (Grade 3 or 4) Sunitinib vs nivolumab + ipilimumab (targeted agent versus combinations of immunotherapy) | RR 1.37 [1.22, 1.53] | 1 study · 1082 participants | Moderate Downgraded: risk of bias, imprecision |
Health‐related quality of life Sunitinib vs nivolumab + ipilimumab (targeted agent versus combinations of immunotherapy) | no estimate extracted | 1 study · 460 participants | Moderate Downgraded: risk of bias, imprecision |
Pazopanib compared to placebo (targeted agent versus placebo)
Population: Previous treated and treatment‐naïve (54%) metastatic renal cell carcinoma (clear cell type)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Progression‐free survival (absolute effect size estimates based on survival rate at 12 months) Pazopanib vs placebo (targeted agent versus placebo) | HR 0.46 [0.34, 0.62] | 1 study · 435 participants | High |
Overall survival (absolute effect size estimates based on survival rate at 24 months) Pazopanib vs placebo (targeted agent versus placebo) | HR 0.91 [0.72, 1.16] | 1 study · 435 participants | Low Downgraded: imprecision |
Serious adverse events (Grade 3 or 4) Pazopanib vs placebo (targeted agent versus placebo) | RR 2 [1.4, 2.85] | 1 study · 435 participants | High |
Health‐related quality of life Pazopanib vs placebo (targeted agent versus placebo) | no estimate extracted | 1 study · 300 participants | High |