studies

melanoma (ML), ipilimumab alone vs. all, meta-analysis of study results

OutcomeTE95% CInkI2ROBPub. bias deaths (OS)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 1.19 [1.00; 1.42] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.59 [1.22; 2.06] CheckMate 067 (NI vs I ; all population), 2015 (REV) 1.82 [1.39; 2.38] CheckMate 069 (all population), 2015 (REV) 1.35 [0.79; 2.31] CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 (REV) 0.69 [0.22; 2.17] CheckMate 238, 2017 0.87 [0.66; 1.14] EORTC 18071, 2015 0.72 [0.58; 0.89] KEYNOTE-006 (2 week), 2015 (REV) 1.59 [1.19; 2.11] KEYNOTE-006 (3 week), 2015 (REV) 1.45 [1.10; 1.91] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.96 [0.77; 1.20] MDX010 Ipi vs gp100, 2010 0.66 [0.51; 0.86] 1.13[0.91; 1.40]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 20101185%5,944lowlow deaths (OS) (extension)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 1.59 [1.31; 1.92] CheckMate 067 (NI vs I ; all population), 2015 (REV) 1.92 [1.56; 2.37] EORTC 18071, 2015 0.73 [0.64; 0.83] KEYNOTE-006 (2 week), 2015 (REV) 1.47 [1.15; 1.88] KEYNOTE-006 (3 week), 2015 (REV) 1.47 [1.15; 1.87] 1.36[0.90; 2.06]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), EORTC 18071, 2015, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)596%3,323lowserious MFSdetailed resultsCheckMate 238, 2017 0.73 [0.56; 0.96] EORTC 18071, 2015 0.76 [0.63; 0.91] 0.75[0.65; 0.87]CheckMate 238, 2017, EORTC 18071, 201520%1,686lownot evaluable MFS (extension)detailed resultsEORTC 18071, 2015 0.76 [0.64; 0.90] 0.76[0.64; 0.90]EORTC 18071, 201510%951NAnot evaluable PFS (extension)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 1.89 [1.56; 2.28] CheckMate 067 (NI vs I ; all population), 2015 (REV) 2.38 [1.97; 2.87] CheckMate 069 (all population), 2015 (REV) 2.78 [1.74; 4.43] CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 (REV) 2.14 [0.44; 10.39] KEYNOTE-006 (2 week), 2015 (REV) 1.64 [1.34; 2.01] KEYNOTE-006 (3 week), 2015 (REV) 1.64 [1.34; 2.01] 1.94[1.64; 2.29]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)659%2,547lownot evaluable progression or deaths (PFS)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 1.12 [0.83; 1.52] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.75 [1.32; 2.33] CheckMate 067 (NI vs I ; all population), 2015 (REV) 2.38 [1.76; 3.23] CheckMate 069 (all population), 2015 (REV) 2.63 [1.59; 4.36] CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 (REV) 2.63 [1.02; 6.79] CheckMate 069 (BRAF wild type), 2015 (REV) 2.50 [1.45; 4.30] KEYNOTE-006 (2 week), 2015 (REV) 1.72 [1.38; 2.16] KEYNOTE-006 (3 week), 2015 (REV) 1.72 [1.39; 2.13] 1.84[1.53; 2.22]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 (REV), CheckMate 069 (BRAF wild type), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)858%3,383lownot evaluable RFS (extension)detailed resultsCheckMate 238, 2017 0.71 [0.59; 0.85] EORTC 18071, 2015 0.75 [0.63; 0.89] 0.73[0.65; 0.83]CheckMate 238, 2017, EORTC 18071, 201520%1,857lownot evaluable RFS/DFSdetailed resultsCheckMate 238, 2017 0.65 [0.51; 0.83] EORTC 18071, 2015 0.75 [0.63; 0.89] 0.72[0.62; 0.82]CheckMate 238, 2017, EORTC 18071, 201520%1,857lownot evaluable DCRdetailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.84 [0.61; 1.16] 0.84[0.61; 1.16]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV)10%727NAnot evaluable objective responses (ORR)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.76 [0.50; 1.17] CheckMate 067 (N vs I ; all population), 2015 (REV) 0.29 [0.17; 0.49] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.16 [0.10; 0.28] CheckMate 069 (all population), 2015 (REV) 0.07 [0.04; 0.12] CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 (REV) 0.10 [0.00; 2.21] CheckMate 069 (BRAF wild type), 2015 (REV) 0.08 [0.02; 0.29] KEYNOTE-006 (2 week), 2015 (REV) 0.27 [0.17; 0.41] KEYNOTE-006 (3 week), 2015 (REV) 0.28 [0.18; 0.43] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 2.03 [1.03; 4.02] MDX010 Ipi vs gp100, 2010 8.24 [1.85; 36.76] 0.35[0.18; 0.69]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 (REV), CheckMate 069 (BRAF wild type), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 20101091%4,196lowlow objective responses (ORR) (extension)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 0.28 [0.20; 0.41] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.16 [0.11; 0.23] CheckMate 069 (all population), 2015 (REV) 0.08 [0.03; 0.23] CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 (REV) 0.10 [0.00; 2.20] CheckMate 069 (BRAF wild type), 2015 (REV) 0.08 [0.02; 0.29] 0.16[0.09; 0.27]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 (REV), CheckMate 069 (BRAF wild type), 2015 (REV)560%1,544lownot evaluable AE (any grade)detailed resultsCheckMate 238, 2017 0.49 [0.20; 1.23] EORTC 18071, 2015 7.53 [3.17; 17.90] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.51 [0.14; 1.83] MDX010 Ipi vs gp100, 2010 0.99 [0.24; 4.05] 1.21[0.28; 5.25]CheckMate 238, 2017, EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010486%2,624lownot evaluable AE (grade 3-4)detailed resultsCheckMate 238, 2017 0.28 [0.21; 0.37] EORTC 18071, 2015 0.11 [0.08; 0.17] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.01 [0.68; 1.51] MDX010 Ipi vs gp100, 2010 0.95 [0.59; 1.55] 0.42[0.16; 1.10]CheckMate 238, 2017, EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010496%2,624lownot evaluable AE leading to treatment discontinuation (any grade)detailed resultsCheckMate 238, 2017 0.15 [0.10; 0.21] 0.15[0.10; 0.21]CheckMate 238, 201710%905NAnot evaluable AE leading to treatment discontinuation (grade 3-4)detailed resultsCheckMate 238, 2017 0.11 [0.07; 0.18] 0.11[0.07; 0.18]CheckMate 238, 201710%905NAnot evaluable STRAE (any grade)detailed resultsKEYNOTE-006 (2 week), 2015 (REV) 1.49 [0.92; 2.42] KEYNOTE-006 (3 week), 2015 (REV) 1.59 [0.97; 2.60] 1.54[1.09; 2.17]KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)20%1,067moderatenot evaluable STRAE (grade 3-4)detailed resultsKEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 1.08[0.07; 17.38]KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)20%1,067moderatenot evaluable TRAE (any grade)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.42 [0.31; 0.57] CheckMate 067 (N vs I ; all population), 2015 (REV) 0.99 [0.63; 1.56] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.27 [0.14; 0.51] CheckMate 069 (all population), 2015 (REV) 1.33 [0.34; 5.28] CheckMate 238, 2017 0.25 [0.15; 0.43] EORTC 18071, 2015 14.40 [10.07; 20.60] KEYNOTE-006 (2 week), 2015 (REV) 0.62 [0.41; 0.93] KEYNOTE-006 (3 week), 2015 (REV) 0.86 [0.58; 1.28] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.50 [0.29; 0.86] MDX010 Ipi vs gp100, 2010 1.09 [0.60; 1.98] 0.83[0.35; 1.95]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 20101097%5,805lowlow TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.37 [0.25; 0.54] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.40 [0.97; 2.03] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.26 [0.19; 0.37] CheckMate 069 (all population), 2015 (REV) 0.26 [0.12; 0.58] CheckMate 238, 2017 0.20 [0.14; 0.27] EORTC 18071, 2015 25.27 [14.14; 45.18] KEYNOTE-006 (2 week), 2015 (REV) 1.19 [0.77; 1.85] KEYNOTE-006 (3 week), 2015 (REV) 1.22 [0.78; 1.90] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.86 [0.50; 1.48] MDX010 Ipi vs gp100, 2010 1.41 [0.69; 2.88] 0.89[0.40; 1.94]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 20101097%5,805lowlow TRAE leading to death (grade 5)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.50 [0.09; 2.75] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] CheckMate 067 (NI vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] CheckMate 238, 2017 0.25 [0.01; 5.55] EORTC 18071, 2015 10.16 [0.55; 186.52] KEYNOTE-006 (2 week), 2015 (REV) 0.54 [0.02; 16.23] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 0.83[0.28; 2.46]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)70%4,891lownot evaluable TRAE leading to discontinuation (any grade)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.51 [0.36; 0.72] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.40 [0.88; 2.21] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.25 [0.17; 0.37] CheckMate 069 (all population), 2015 (REV) 0.24 [0.10; 0.57] CheckMate 069 (BRAF wild type), 2015 (REV) 0.30 [0.12; 0.71] CheckMate 238, 2017 0.12 [0.08; 0.17] EORTC 18071, 2015 21.35 [13.41; 33.97] KEYNOTE-006 (2 week), 2015 (REV) 1.35 [0.71; 2.53] KEYNOTE-006 (3 week), 2015 (REV) 0.81 [0.46; 1.44] 0.69[0.24; 2.01]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 069 (BRAF wild type), 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)998%5,139lownot evaluable TRAE leading to discontinuation (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.44 [0.30; 0.66] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.93 [1.14; 3.27] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.37 [0.25; 0.55] CheckMate 069 (all population), 2015 (REV) 0.24 [0.09; 0.63] CheckMate 238, 2017 0.09 [0.05; 0.15] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 0.40[0.17; 0.98]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)791%4,086lownot evaluable Abdominal pain TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 4.05 [0.18; 90.07] CheckMate 067 (NI vs I ; all population), 2015 (REV) 2.02 [0.18; 22.39] CheckMate 069 (all population), 2015 (REV) 4.16 [0.14; 126.20] CheckMate 238, 2017 0.50 [0.02; 14.96] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 1.80[0.48; 6.69]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)60%3,360lownot evaluable Adrenal insufficiency TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.50 [0.02; 15.01] CheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.05; 5.56] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.17 [0.02; 1.38] CheckMate 069 (all population), 2015 (REV) 4.23 [0.37; 47.88] CheckMate 238, 2017 0.50 [0.09; 2.74] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.72 [0.03; 16.16] MDX010 Ipi vs gp100, 2010 1.01 [0.02; 51.17] 0.59[0.24; 1.50]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 201070%3,793lownot evaluable Alopecia TRAE (grade 3-4)detailed resultsKEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 1.08[0.07; 17.38]KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)20%1,067moderatenot evaluable Anaemia TRAE (grade 3-4)detailed resultsKEYNOTE-006 (2 week), 2015 (REV) 0.54 [0.05; 6.00] KEYNOTE-006 (3 week), 2015 (REV) 2.17 [0.07; 64.92] 0.86[0.12; 6.13]KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)20%1,067moderatenot evaluable Arthralgia TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.25 [0.01; 5.58] CheckMate 069 (all population), 2015 (REV) 2.05 [0.04; 105.24] CheckMate 238, 2017 0.50 [0.05; 5.53] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 0.62[0.16; 2.37]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)60%3,360lownot evaluable Asthenia TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 2.02 [0.18; 22.39] CheckMate 067 (NI vs I ; all population), 2015 (REV) 2.02 [0.18; 22.39] CheckMate 069 (all population), 2015 (REV) 2.05 [0.04; 105.24] CheckMate 238, 2017 0.25 [0.03; 2.24] KEYNOTE-006 (2 week), 2015 (REV) 2.18 [0.20; 24.20] KEYNOTE-006 (3 week), 2015 (REV) 4.35 [0.20; 97.02] 1.38[0.48; 3.97]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)60%3,360lownot evaluable Chills TRAE (grade 3-4)detailed resultsCheckMate 069 (all population), 2015 (REV) 2.05 [0.04; 105.24] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 1.34[0.14; 12.95]CheckMate 069 (all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)30%1,207moderatenot evaluable Colitis TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.46 [0.21; 1.04] CheckMate 067 (N vs I ; all population), 2015 (REV) 8.64 [2.57; 29.01] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.92 [0.52; 1.65] CheckMate 069 (all population), 2015 (REV) 0.34 [0.09; 1.23] EORTC 18071, 2015 39.14 [5.34; 286.74] KEYNOTE-006 (2 week), 2015 (REV) 5.18 [1.73; 15.52] KEYNOTE-006 (3 week), 2015 (REV) 2.92 [1.20; 7.11] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.73 [0.67; 4.49] MDX010 Ipi vs gp100, 2010 14.85 [0.83; 264.38] 2.35[1.02; 5.42]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), EORTC 18071, 2015, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010982%4,900lowserious Constipation TRAE (grade 3-4)detailed resultsCheckMate 069 (all population), 2015 (REV) 1.02 [0.03; 31.03] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 1.06[0.12; 9.12]CheckMate 069 (all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)30%1,207moderatenot evaluable Cough TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 0.25 [0.01; 5.58] CheckMate 067 (NI vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 0.64[0.10; 3.99]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)40%2,315lownot evaluable Decreased appetite TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 2.02 [0.07; 60.32] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.25 [0.03; 2.24] CheckMate 069 (all population), 2015 (REV) 2.05 [0.04; 105.24] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 0.71[0.17; 2.95]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)50%2,455lowserious Diabetes TRAE (grade 3-4)detailed resultsCheckMate 238, 2017 2.01 [0.07; 59.97] KEYNOTE-006 (3 week), 2015 (REV) 0.54 [0.02; 16.17] 1.04[0.09; 11.51]CheckMate 238, 2017, KEYNOTE-006 (3 week), 2015 (REV)20%1,438lownot evaluable Diarrhoea TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.54 [0.31; 0.95] CheckMate 067 (N vs I ; all population), 2015 (REV) 2.08 [0.92; 4.69] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.60 [0.33; 1.11] CheckMate 069 (all population), 2015 (REV) 1.02 [0.33; 3.19] CheckMate 238, 2017 0.15 [0.07; 0.34] EORTC 18071, 2015 25.54 [6.16; 105.87] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.38; 3.15] KEYNOTE-006 (3 week), 2015 (REV) 2.57 [0.66; 10.04] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.25 [0.47; 3.34] MDX010 Ipi vs gp100, 2010 6.29 [0.75; 52.98] 1.28[0.62; 2.67]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 20101084%5,805lowcritical Dry skin TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.73 [0.33; 1.61] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 0.76[0.36; 1.61]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)40%2,315lownot evaluable Dyspnoea TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.17 [0.01; 3.34] CheckMate 069 (all population), 2015 (REV) 0.33 [0.02; 6.80] KEYNOTE-006 (2 week), 2015 (REV) 2.18 [0.07; 65.16] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.07; 17.40] 0.56[0.14; 2.24]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)50%2,455lownot evaluable Endocrine disorders TRAE (grade 3-4) detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.43 [0.19; 1.01] CheckMate 069 (all population), 2015 (REV) 0.81 [0.15; 4.34] EORTC 18071, 2015 42.70 [5.84; 312.15] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 3.73 [0.99; 14.11] MDX010 Ipi vs gp100, 2010 10.44 [0.56; 193.00] 2.98[0.56; 15.74]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 069 (all population), 2015 (REV), EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010583%2,585lownot evaluable Eye disorders TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 2.01 [0.07; 60.22] 2.01[0.07; 60.22]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV)10%726NAnot evaluable Fatigue TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.20; 5.03] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.22 [0.06; 0.80] CheckMate 069 (all population), 2015 (REV) 0.20 [0.01; 3.66] CheckMate 238, 2017 0.50 [0.09; 2.74] KEYNOTE-006 (2 week), 2015 (REV) 3.28 [0.34; 31.78] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.22; 5.41] 0.61[0.28; 1.33]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)616%3,360lownot evaluable Febrile neutropenia TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.25 [0.01; 5.57] 0.25[0.01; 5.57]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV)10%726NAnot evaluable Gastrointestinal disorders TRAE (grade 3-4) detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.55 [0.34; 0.88] CheckMate 069 (all population), 2015 (REV) 0.45 [0.16; 1.29] CheckMate 238, 2017 0.10 [0.05; 0.20] EORTC 18071, 2015 22.61 [8.20; 62.34] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.34 [0.62; 2.92] MDX010 Ipi vs gp100, 2010 10.83 [1.37; 85.84] 1.28[0.31; 5.21]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010694%3,490lownot evaluable Guillain-Barré syndrome TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.25 [0.01; 5.57] 0.25[0.01; 5.57]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV)10%726NAnot evaluable Headache TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 2.02 [0.07; 60.32] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.50 [0.05; 5.56] CheckMate 069 (all population), 2015 (REV) 0.51 [0.02; 11.44] CheckMate 238, 2017 0.14 [0.02; 1.15] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 0.46[0.14; 1.49]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)60%3,360lowserious Hepatitis TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.40 [0.08; 2.07] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.10 [0.01; 1.82] CheckMate 069 (all population), 2015 (REV) 0.33 [0.02; 6.80] KEYNOTE-006 (2 week), 2015 (REV) 0.36 [0.04; 3.48] KEYNOTE-006 (3 week), 2015 (REV) 0.21 [0.02; 1.84] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.45 [0.05; 43.54] MDX010 Ipi vs gp100, 2010 1.01 [0.02; 51.17] 0.37[0.15; 0.90]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 201080%3,955lownot evaluable Hepatobiliary disorders TRAE (grade 3-4) detailed resultsCheckMate 069 (all population), 2015 (REV) 0.06 [0.00; 1.08] CheckMate 238, 2017 0.15 [0.07; 0.32] EORTC 18071, 2015 57.44 [7.90; 417.44] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.36 [0.02; 6.86] MDX010 Ipi vs gp100, 2010 0.16 [0.01; 3.32] 0.53[0.04; 7.00]CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010587%2,764lownot evaluable Hypersensitivity TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.17 [0.01; 3.33] CheckMate 238, 2017 2.01 [0.07; 59.97] 0.51[0.04; 5.72]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 238, 2017214%1,631lownot evaluable Hyperthyroidism TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.17 [0.01; 3.34] CheckMate 069 (all population), 2015 (REV) 2.05 [0.04; 105.24] CheckMate 238, 2017 1.00 [0.06; 16.07] KEYNOTE-006 (2 week), 2015 (REV) 2.18 [0.07; 65.16] KEYNOTE-006 (3 week), 2015 (REV) 2.17 [0.07; 64.92] 0.97[0.25; 3.75]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)60%3,360lownot evaluable Hypophysitis TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.70 [0.26; 1.85] CheckMate 067 (N vs I ; all population), 2015 (REV) 5.10 [0.59; 43.89] CheckMate 067 (NI vs I ; all population), 2015 (REV) 1.01 [0.29; 3.51] CheckMate 069 (all population), 2015 (REV) 2.09 [0.29; 15.34] CheckMate 238, 2017 0.18 [0.04; 0.81] EORTC 18071, 2015 44.19 [2.67; 732.31] KEYNOTE-006 (2 week), 2015 (REV) 4.37 [0.20; 97.37] KEYNOTE-006 (3 week), 2015 (REV) 2.17 [0.20; 24.11] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 2.93 [0.41; 21.02] MDX010 Ipi vs gp100, 2010 4.08 [0.18; 91.29] 1.67[0.72; 3.91]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 20101050%5,805lowcritical Hypothyroidism TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.50 [0.02; 15.01] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03] CheckMate 069 (all population), 2015 (REV) 2.05 [0.04; 105.24] CheckMate 238, 2017 0.50 [0.05; 5.53] KEYNOTE-006 (2 week), 2015 (REV) 0.54 [0.02; 16.23] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.45 [0.05; 43.54] MDX010 Ipi vs gp100, 2010 1.01 [0.02; 51.17] 0.77[0.25; 2.38]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 201090%4,860lowserious Increase AST TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.12 [0.02; 0.99] CheckMate 067 (N vs I ; all population), 2015 (REV) 0.67 [0.11; 4.03] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.10 [0.02; 0.43] CheckMate 069 (all population), 2015 (REV) 0.14 [0.01; 2.46] CheckMate 238, 2017 0.10 [0.02; 0.44] KEYNOTE-006 (2 week), 2015 (REV) 4.37 [0.20; 97.37] KEYNOTE-006 (3 week), 2015 (REV) 2.17 [0.20; 24.11] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.45 [0.05; 43.54] MDX010 Ipi vs gp100, 2010 1.01 [0.02; 51.17] 0.33[0.13; 0.85]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010936%4,860lowserious Increased ALT TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.16 [0.04; 0.73] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.26 [0.34; 4.75] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.17 [0.07; 0.46] CheckMate 069 (all population), 2015 (REV) 0.09 [0.01; 1.62] CheckMate 238, 2017 0.18 [0.07; 0.48] KEYNOTE-006 (2 week), 2015 (REV) 4.37 [0.20; 97.37] KEYNOTE-006 (3 week), 2015 (REV) 2.17 [0.20; 24.11] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.72 [0.03; 16.16] MDX010 Ipi vs gp100, 2010 1.01 [0.02; 51.17] 0.38[0.17; 0.85]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010944%4,860lownot evaluable Increased lipase level TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.50 [0.02; 15.01] CheckMate 067 (N vs I ; all population), 2015 (REV) 0.86 [0.39; 1.88] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.33 [0.17; 0.65] CheckMate 069 (all population), 2015 (REV) 0.24 [0.03; 1.97] 0.48[0.26; 0.88]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV)419%2,114lownot evaluable Infusion-related reactions TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.25 [0.01; 5.57] 0.25[0.01; 5.57]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV)10%726NAnot evaluable Maculopapular rash TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.50 [0.02; 15.01] CheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.05; 5.56] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.17 [0.02; 1.38] CheckMate 069 (all population), 2015 (REV) 0.33 [0.02; 6.80] CheckMate 238, 2017 0.05 [0.00; 0.95] KEYNOTE-006 (2 week), 2015 (REV) 2.18 [0.07; 65.16] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.07; 17.40] 0.35[0.12; 0.98]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)70%4,086lownot evaluable Myalgia TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03] CheckMate 069 (all population), 2015 (REV) 2.05 [0.04; 105.24] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.07; 17.46] KEYNOTE-006 (3 week), 2015 (REV) 2.17 [0.07; 64.92] 1.01[0.23; 4.46]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)50%2,455lownot evaluable Myositis TRAE (grade 3-4)detailed resultsKEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 1.08[0.07; 17.38]KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)20%1,067moderatenot evaluable Nausea TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 4.05 [0.18; 90.07] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.28 [0.06; 1.37] CheckMate 069 (all population), 2015 (REV) 2.07 [0.13; 33.80] CheckMate 238, 2017 2.01 [0.07; 59.97] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 0.79[0.27; 2.35]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)60%3,360lowserious Nephritis TRAE (grade 3-4)detailed resultsKEYNOTE-006 (2 week), 2015 (REV) 2.18 [0.07; 65.16] KEYNOTE-006 (3 week), 2015 (REV) 2.17 [0.07; 64.92] 2.17[0.20; 24.03]KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)20%1,067moderatenot evaluable Nervous system disorders TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.12 [0.01; 2.36] EORTC 18071, 2015 18.45 [1.07; 319.15] 1.54[0.01; 206.07]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), EORTC 18071, 2015283%1,671lownot evaluable Neutropenia TRAE (grade 3-4)detailed resultsKEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 1.08[0.07; 17.38]KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)20%1,067moderatenot evaluable Pancreatitis TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.50 [0.02; 15.01] 0.50[0.02; 15.01]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV)10%726NAnot evaluable Pancytopenia TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.50 [0.02; 15.01] 0.50[0.02; 15.01]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV)10%726NAnot evaluable Paraesthesia TRAE (grade 3-4)detailed resultsKEYNOTE-006 (2 week), 2015 (REV) 2.18 [0.07; 65.16] KEYNOTE-006 (3 week), 2015 (REV) 2.17 [0.07; 64.92] 2.17[0.20; 24.03]KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)20%1,067moderatenot evaluable Pericarditis TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.50 [0.02; 15.01] 0.50[0.02; 15.01]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV)10%726NAnot evaluable Peripheral neuropathy TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.25 [0.01; 5.57] 0.25[0.01; 5.57]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV)10%726NAnot evaluable Pneumonitis TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.12 [0.01; 2.36] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.06; 16.16] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.33 [0.03; 3.22] CheckMate 069 (all population), 2015 (REV) 1.02 [0.09; 11.57] KEYNOTE-006 (2 week), 2015 (REV) 2.18 [0.07; 65.16] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.07; 17.40] 0.64[0.21; 1.92]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)60%3,181lownot evaluable Polymyalgia Rheumatica TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 2.01 [0.07; 60.22] 2.01[0.07; 60.22]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV)10%726NAnot evaluable Pruritic rash TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 2.01 [0.07; 60.22] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] CheckMate 067 (NI vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] CheckMate 069 (all population), 2015 (REV) 2.05 [0.04; 105.24] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 1.33[0.28; 6.35]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)60%3,181lownot evaluable Pruritus TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 1.01 [0.14; 7.18] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.06; 16.16] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.17 [0.02; 1.38] CheckMate 069 (all population), 2015 (REV) 1.02 [0.03; 31.03] CheckMate 238, 2017 0.10 [0.01; 1.82] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.45 [0.05; 43.54] MDX010 Ipi vs gp100, 2010 1.01 [0.02; 51.17] 0.57[0.22; 1.47]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 201090%4,860lownot evaluable Pyrexia TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 2.02 [0.07; 60.32] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.50 [0.05; 5.56] CheckMate 069 (all population), 2015 (REV) 0.33 [0.02; 6.80] CheckMate 238, 2017 0.25 [0.01; 5.55] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 0.60[0.16; 2.16]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)60%3,360lownot evaluable Rash TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.40 [0.08; 2.07] CheckMate 067 (N vs I ; all population), 2015 (REV) 5.10 [0.59; 43.89] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.50 [0.17; 1.47] CheckMate 069 (all population), 2015 (REV) 0.20 [0.01; 3.66] CheckMate 238, 2017 0.35 [0.13; 0.98] EORTC 18071, 2015 10.16 [0.55; 186.52] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.58 [0.07; 4.98] MDX010 Ipi vs gp100, 2010 2.02 [0.07; 60.83] 0.64[0.34; 1.22]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 20101010%5,805lowlow Renal and urinary disorders TRAE (grade 3-4) detailed resultsCheckMate 069 (all population), 2015 (REV) 1.02 [0.03; 31.03] CheckMate 238, 2017 1.00 [0.02; 50.62] 1.01[0.08; 13.30]CheckMate 069 (all population), 2015 (REV), CheckMate 238, 201720%1,045lownot evaluable Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.12 [0.01; 2.36] CheckMate 069 (all population), 2015 (REV) 0.67 [0.07; 6.66] CheckMate 238, 2017 0.12 [0.01; 2.36] 0.27[0.06; 1.25]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 201730%1,771lownot evaluable Skin and subcutaneous tissue disorders TRAE (grade 3-4) detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.71 [0.22; 2.27] CheckMate 069 (all population), 2015 (REV) 0.10 [0.01; 1.83] CheckMate 238, 2017 0.18 [0.07; 0.46] EORTC 18071, 2015 42.00 [2.53; 697.02] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.64 [0.14; 3.00] MDX010 Ipi vs gp100, 2010 4.08 [0.18; 91.29] 0.80[0.21; 3.02]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 069 (all population), 2015 (REV), CheckMate 238, 2017, EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010671%3,490lownot evaluable Thyroiditis TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 0.50 [0.02; 15.01] CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03] 0.61[0.08; 4.71]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV)30%1,974lownot evaluable Uveitis TRAE (grade 3-4)detailed resultsAscierto (ipi 10 vs 3 mg/kg), 2017 (REV) 2.01 [0.07; 60.22] KEYNOTE-006 (2 week), 2015 (REV) 1.09 [0.02; 54.94] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 1.39[0.16; 11.91]Ascierto (ipi 10 vs 3 mg/kg), 2017 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)30%1,793moderatenot evaluable Vitiligo TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03] CheckMate 067 (NI vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88] CheckMate 069 (all population), 2015 (REV) 2.05 [0.04; 105.24] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 2.91 [0.06; 147.31] MDX010 Ipi vs gp100, 2010 1.01 [0.02; 51.17] 1.18[0.22; 6.46]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 201050%2,162lownot evaluable Vomiting TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.06; 16.16] CheckMate 067 (NI vs I ; all population), 2015 (REV) 0.14 [0.02; 1.15] CheckMate 069 (all population), 2015 (REV) 1.02 [0.03; 31.03] KEYNOTE-006 (2 week), 2015 (REV) 0.54 [0.02; 16.23] KEYNOTE-006 (3 week), 2015 (REV) 1.08 [0.02; 54.74] 0.44[0.12; 1.61]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), CheckMate 069 (all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)50%2,455lowserious Weight decreased TRAE (grade 3-4)detailed resultsCheckMate 067 (N vs I ; all population), 2015 (REV) 2.02 [0.07; 60.32] CheckMate 067 (NI vs I ; all population), 2015 (REV) 2.02 [0.07; 60.32] KEYNOTE-006 (2 week), 2015 (REV) 2.18 [0.07; 65.16] KEYNOTE-006 (3 week), 2015 (REV) 2.17 [0.07; 64.92] 2.09[0.38; 11.45]CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 067 (NI vs I ; all population), 2015 (REV), KEYNOTE-006 (2 week), 2015 (REV), KEYNOTE-006 (3 week), 2015 (REV)40%2,315lownot evaluable Abdominal pain AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.04 [0.01; 0.17] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.97 [0.19; 4.85] MDX010 Ipi vs gp100, 2010 0.28 [0.06; 1.36] 0.21[0.03; 1.36]EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010377%1,719lownot evaluable Anaemia AE (grade 3-4)detailed resultsMDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.06 [0.33; 3.38] MDX010 Ipi vs gp100, 2010 0.35 [0.11; 1.12] 0.61[0.20; 1.81]MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010243%774lownot evaluable Colitis AE (grade 3-4)detailed resultsEORTC 18071, 2015 6.26 [2.61; 15.03] 6.26[2.61; 15.03]EORTC 18071, 201510%945NAnot evaluable Constipation AE (grade 3-4)detailed resultsMDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 2.95 [0.59; 14.78] MDX010 Ipi vs gp100, 2010 3.07 [0.32; 29.91] 2.99[0.80; 11.14]MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 201020%774lownot evaluable Cough AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.01 [0.00; 0.15] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.45 [0.05; 43.54] MDX010 Ipi vs gp100, 2010 1.01 [0.02; 51.17] 0.20[0.01; 6.38]EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010369%1,719lownot evaluable Decreased appetite AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.06 [0.01; 0.46] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.97 [0.19; 4.85] MDX010 Ipi vs gp100, 2010 0.50 [0.09; 2.76] 0.34[0.07; 1.59]EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010356%1,719lownot evaluable Diarrhoea AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.26 [0.18; 0.37] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.21 [0.49; 2.98] MDX010 Ipi vs gp100, 2010 7.40 [0.90; 60.98] 1.01[0.20; 5.07]EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010389%1,719lownot evaluable Dyspnoea AE (grade 3-4)detailed resultsMDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.04 [0.37; 2.94] MDX010 Ipi vs gp100, 2010 0.83 [0.25; 2.80] 0.95[0.43; 2.08]MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 201020%774lownot evaluable Fatigue AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.05 [0.03; 0.10] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.40 [0.62; 3.18] MDX010 Ipi vs gp100, 2010 2.36 [0.71; 7.87] 0.53[0.04; 6.96]EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010396%1,719lownot evaluable Headache AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.04 [0.01; 0.11] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 2.20 [0.49; 9.98] MDX010 Ipi vs gp100, 2010 1.01 [0.20; 5.09] 0.42[0.03; 6.30]EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010392%1,719lownot evaluable Hypophysitis AE (grade 3-4)detailed resultsEORTC 18071, 2015 11.01 [2.57; 47.24] 11.01[2.57; 47.24]EORTC 18071, 201510%945NAnot evaluable Hypothyroidism AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.14 [0.02; 1.16] 0.14[0.02; 1.16]EORTC 18071, 201510%945NAnot evaluable Increase AST AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.80 [0.45; 1.45] 0.80[0.45; 1.45]EORTC 18071, 201510%945NAnot evaluable Increased ALT AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.97 [0.55; 1.70] 0.97[0.55; 1.70]EORTC 18071, 201510%945NAnot evaluable Nausea AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.01 [0.00; 0.07] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 1.46 [0.36; 5.93] MDX010 Ipi vs gp100, 2010 1.01 [0.20; 5.09] 0.26[0.02; 4.55]EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 2010389%1,719lownot evaluable Pruritus AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.14 [0.07; 0.26] 0.14[0.07; 0.26]EORTC 18071, 201510%945NAnot evaluable Pyrexia AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.21 [0.08; 0.56] MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV) 0.72 [0.03; 16.16] MDX010 Ipi vs gp100, 2010 0.25 [0.01; 5.58] 0.24[0.10; 0.58]EORTC 18071, 2015, MDX010 Ipi plus gp100 vs Ipi (EXPLORATORY), 2010 (REV), MDX010 Ipi vs gp100, 201030%1,719lownot evaluable Rash AE (grade 3-4)detailed resultsEORTC 18071, 2015 0.06 [0.03; 0.15] 0.06[0.03; 0.15]EORTC 18071, 201510%945NAnot evaluable0.020.01.0relative treatment effectwww.metaEvidence.org2024-05-25 10:28 +02:00

TE: relative treatment effect (measured by a risk ratio, an odds ratio or an hazard ratio depending on what is reported in the papers); k: number of studies; n: total number of patients; ROB: risk of bias (ROB 2.0); Pub. bias: publication bias; OBS: observational studies; RCT: randomized clinical trials
studied treatment is better when TE > 1; studied treatment is better when TE < 1;

pathologies: 2,283,284,70,235,285,68,127,128,286,69,129 - treatments: 329,558