Table 3 Adverse event rates by approved first-line anti-angiogenic and molecularly targeted therapeutic agents in the treatment of good and intermediate risk metastatic clear cell renal cell carcinoma

Any grade 3, 4, or 5

0.544 (0.505-0.582)

0.705 (0.670-0.738)

0.734 (0.695-0.769)

0.744 (0.706-0.778)

AE leading to discontinuation of drug

0.185 (0.158-0.217)

0.282 (0.237-0.332)

0.197 (0.173-0.224)

0.244 (0.210-0.281)

AE leading to death

0.013 (0.008-0.022)

0.016 (0.009-0.028)

0.022 (0.014-0.033)

0.023 (0.014-0.040)

Thrombocytopenia

0.135 (0.115-0.157)

0.084 (0.066-0.107)

0.732 (0.703-0.760)

0.410 (0.370-0.451)

Grade ≥ 3

0.009 (0.005-0.017)

0.021 (0.013-0.035)

0.164 (0.141-0.189)

0.036 (0.023-0.055)

Neutropenia

0.320 (0.292-0.350)

0.260 (0.229-0.294)

0.714 (0.684-0.742)

0.366 (0.327-0.407)

Grade ≥ 3

0.069 (0.055-0.087)

0.069 (0.052-0.090)

0.192 (0.168-0.218)

0.045 (0.031-0.066)

Anemia

0.365 (0.336-0.395)

0.132 (0.109-0.159)

0.674 (0.643-0.703)

0.309 (0.272-0.348)

Grade ≥ 3

0.051 (0.039-0.067)

0.033 (0.022-0.049)

0.076 (0.060-0.095)

0.022 (0.012-0.037)

Asthenic conditions or fatigue

0.576 (0.545-0.606)

0.638 (0.602-0.673)

0.593 (0.561-0.624)

0.545 (0.503-0.586)

Grade ≥ 3

0.178 (0.156-0.203)

0.250 (0.220-0.284)

0.146 (0.125-0.171)

0.106 (0.083-0.135)

Diarrhea

0.152 (0.127-0.181)

0.205 (0.165-0.251)

0.589 (0.557-0.621)

0.628 (0.587-0.667)

Grade ≥ 3

0.011 (0.005-0.022)

0.021 (0.010-0.042)

0.082 (0.066-0.102)

0.088 (0.068-0.115)

Nausea

0.467 (0.430-0.504)

0.580 (0.529-0.630)

0.482 (0.450-0.514)

0.446 (0.405-0.487)

Grade ≥ 3

0.030 (0.020-0.045)

0.072 (0.049-0.103)

0.034 (0.024-0.047)

0.022 (0.012-0.037)

Anorexia or appetite loss

0.402 (0.372-0.432)

0.542 (0.505-0.579)

0.358 (0.327-0.389)

0.374 (0.334-0.415)

Grade ≥ 3

0.043 (0.032-0.057)

0.104 (0.084-0.129)

0.029 (0.020-0.042)

0.014 (0.007-0.028)

HTN

0.054 (0.042-0.070)

0.273 (0.242-0.307)

0.364 (0.334-0.396)

0.464 (0.423-0.506)

Grade ≥ 3

0.006 (0.003-0.013)

0.072 (0.055-0.093)

0.137 (0.116-0.160)

0.148 (0.121-0.180)

Proteinuria

0.049 (0.035-0.069)

0.452 (0.416-0.489)

0.137 (0.111-0.168)

0.177 (0.147-0.211)

Grade ≥ 3

0.002 (0.000-0.009)

0.112 (0.090-0.137)

0.040 (0.027-0.060)

0.042 (0.028-0.062)

Pyrexia

0.386 (0.349-0.423)

0.451 (0.399-0.504)

0.128 (0.108-0.151)

0.087 (0.066-0.113)

Grade ≥ 3

0.009 (0.004-0.020)

0.024 (0.012-0.046)

0.011 (0.006-0.020)

0.004 (0.001-0.013)

Headache

0.161 (0.135-0.191)

0.234 (0.192-0.282)

0.186 (0.163-0.213)

0.227 (0.194-0.264)

Grade ≥ 3

0.006 (0.002-0.015)

0.021 (0.010-0.042)

0.011 (0.006-0.020)

0.027 (0.016-0.044)

Thyroid dysfunction

0.010 (0.005-0.020)

0.006 (0.002-0.020)

0.202 (0.177-0.229)

0.121 (0.096-0.151)

Grade ≥ 3

0.006 (0.002-0.014)

0.006 (0.002-0.020)

0.011 (0.006-0.020)

0.000 (0.000-0.007)

Weight loss

0.130 (0.107-0.157)

0.157 (0.124-0.199)

0.085 (0.068-0.104)

0.152 (0.124-0.184)

Grade ≥ 3

0.013 (0.007-0.024)

0.041 (0.025-0.067)

0.005 (0.002-0.013)

0.009 (0.004-0.021)

Dyspnea

0.098 (0.081-0.118)

0.139 (0.115-0.166)

0.143 (0.122-0.167)

0.137 (0.111-0.168)

Grade ≥ 3

0.026 (0.018-0.037)

0.036 (0.024-0.052)

0.023 (0.015-0.035)

0.025 (0.015-0.042)