Table 1.
Studies included in the multiple-treatment meta-analysis
| Study | Patients (n) | Age (years) median (range) | Sex (% male) | Favourable | MSKCC (%) Intermediate | Poor | Median PFS in months (95% CI) | HR (95% CI) |
| Motzer et al39 (RECORD-3) | ||||||||
| Everolimus | 238 | 62 (20–89) | 69.7 | 29 | 56 | 15 | 7.9 | 1.4 (1.2 to 1.8) |
| Sunitinib | 238 | 62 (29–84) | 73.9 | 30 | 56 | 14 | 10.7 | 1 (Ref) |
| Motzer et al43 (COMPARZ) | ||||||||
| Pazopanib | 557 | 61 (18–88) | 71 | 27 | 58 | 12 | 8.4 (8.3 to 10.9) | 1.05 (0.90 to 1.22) |
| Sunitinib | 553 | 62 (23–86) | 75 | 27 | 59 | 9 | 9.5 (8.3 to 11.1) | 1 (Ref) |
| Rini et al38 (INTORACT) | ||||||||
| Temsirolimus plus bevacizumab | 400 | 59 (22–87) | 72 | 28 | 65 | 8 | 9.1 (8.1 to 10.2) | 1.1 (0.9 to 1.3) |
| Bevacizumab plus IFN-α | 391 | 58 (23–81) | 69 | 27 | 65 | 8 | 9.3 (9.0 to 11.2) | 1 (Ref) |
| Procopio et al42 (ROSORC) | ||||||||
| Sorafenib plus interleukin-2 | 66 | 64 (57–69)* | 79 | 55 | 41 | 5 | NA | NA |
| Sorafenib | 62 | 62 (52–69)* | 69 | 55 | 39 | 6 | NA | NA |
| Hutson et al12 | ||||||||
| Axitinib | 192 | 58 (23–83) | 70 | 49 | 44 | 4 | 10.1 (7.2 to 12.1) | 0.77 (0.56 to 1.05) |
| Sorafenib | 96 | 58 (20–77) | 77 | 55 | 42 | 2 | 6.5 (4.7 to 8.3) | 1 (Ref) |
| Motzer et al13 | ||||||||
| Tivozanib | 260; treatment naive 181 | 59 (23–83) | 71 | 27 | 67 | 7 | 12.7 (9.1 to 15.0) | 0.756 (0.580 to 0.985) |
| Sorafenib | 257; treatment naive 181 | 59 (23–85) | 74 | 34 | 62 | 4 | 9.1 (7.3 to 10.8) | 1 (Ref) |
| Sternberg et al11 (VEG105192) | ||||||||
| Pazopanib | 290; treatment naive 155 | 59 (28–82) | 68 | 36 | 56 | 4 | 11.1 | 0.40 (0.27 to 0.60) |
| Placebo | n=145; treatment naive 78 | 62 (25–81) | 74 | 40 | 51 | 6 | 2.8 | 1 (Ref) |
| Motzer et al36 | ||||||||
| Sunitinib | 375 | 62 (27–87) | 71 | 38 | 56 | 6 | 11 (11 to 13) | 0.539 (0.451 to 0.643) |
| IFN-α | 375 | 59 (34–85) | 72 | 34 | 59 | 7 | 5 (4 to 6) | 1 (Ref) |
| Negrier et al10 (TARGET) | ||||||||
| Sorafenib | 451; treatment naive 77 | 60 | 63.6 | 53.2 | 46.8 | 0 | 5.8 | 0.48 (0.32 to 0.73) |
| Placebo | 452; treatment naive 84 | 60.5 | 69 | 45.2 | 54.8 | 0 | 2.8 | 1 (Ref) |
| Rini et al35 (CALGB 90206) | ||||||||
| Bevacizumab plus IFN-α | 369 | 61 (56–70) | 73 | 26 | 64 | 10 | 8.5 (7.5 to 9.7) | 0.71 (0.61 to 0.83) |
| IFN-α | 363 | 62 (55–70) | 66 | 26 | 64 | 10 | 5.2 (3.1 to 5.6) | 1 (Ref) |
| Escudier et al34 (AVOREN) | ||||||||
| Bevacizumab plus IFN-α | 327 | 61 (30–82) | 68 | 27 | 56 | 9 | 10.2 | 0.61 (0.51 to 0.73) |
| IFN-α | 322 | 60 (18–81) | 73 | 29 | 56 | 8 | 5.4 | 1 (Ref) |
| Motzer et al16 (CheckMate 214) | ||||||||
| Nivolumab plus ipilimumab | 550 | 62 (26–85) | 75 | 23 | 61 | 17 | 11.6 (8.7 to 15.5) | 0.82 (0.64 to 1.05)† |
| Sunitinib | 546 | 62 (21–85) | 72 | 23 | 61 | 16 | 8.4 (7.0 to 10.8) | 1 (Ref) |
| Choueiri et al15 | ||||||||
| Cabozantinib | 79 | 63 (40–82) | 83.5 | 0 | 81.0‡ | 19.0‡ | 8.2 (6.2 to 8.8) | 0.66 (0.46 to 0.95) |
| Sunitinib | 78 | 64 (31–87) | 73.1 | 0 | 80.8‡ | 19.2‡ | 5.6 (3.4 to 8.1) | 1 (Ref) |
| Motzer et al41 (JAVELIN Renal 101) | ||||||||
| Avelumab plus axitinib | 442 | 62 (29–83) | 71.5 | 21.7 | 64 | 11.5 | 13.8 (11.1-NE) | 0.69 (0.56 to 0.84) |
| Sunitinib | 444 | 61 (27–88) | 77.5 | 22.5 | 66 | 10.1 | 8.4 (6.9 to 11.1) | 1 (Ref) |
| Rini et al40 (KEYNOTE-426) | ||||||||
| Pembrolizumab and axitinib | 432 | 62 (30–89) | 71.3 | 31.9‡ | 55.1‡ | 13‡ | 15.1 (12.6 to 17.7) | 0.69 (0.57 to 0.84) |
| Sunitinib | 429 | 61 (26–90) | 74.6 | 30.5‡ | 57.3‡ | 12.1‡ | 11.1 (8.7 to 12.5) | 1 (Ref) |
RECORD-3, COMPARZ, INTORACT, ROSORC, TARGET, CALGB, AVOREN, JAVELIN, and KEYNOTE are names of the trials.
NE denotes could not be estimated.
*IQR.
†99.1% CI.
‡International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group.
CALGB, Cancer and Leukemia Group B; IFN-α, interferon-α; INTORACT, Investigation of Torisel and Avastin Combination Therapy trial; MSKCC, Memorial Sloan Kettering Cancer Center; NA, not available; PFS, progression-free survival; RECORD, Renal Cell Cancer Treatment With Oral RAD001 Given Daily; Ref, reference group (hence HR set to 1); TARGET, Treatment Approaches in Renal Cancer Global Evaluation Trial.