Which Is the Most Appropriate PI3K Inhibitor for Breast Cancer Patients with or without PIK3CA Status Mutant? A Systematic Review and Network Meta-Analysis
Table 3
Adverse events of included RCTs of PI3K inhibitors in treatment of breast cancer.
System
Outcomes
PI3K inhibitor type
Included RCTs
OR (95% CI)
,
Meta-regression
Publication bias
Certainty of evidence
Gastrointestinal disorders
Diarrhoea (all AE)
Overall
6 [19, 21-24, 26]
3.310 (2.211, 4.955)
0.001, 75.6%&
0.015#
0.092, 1.000
Low
Alpelisib
1 [19]
7.350 (4.947, 10.919)
—
Buparlisib
4 [22-24, 28]
2.710 (2.182, 3.366)
0.738, 0.0%
Taselisib
1 [21]
2.786 (1.546, 5.021)
—
Diarrhoea (3-5 AE)
Overall
7 [19, 21-26]
2.438 (1.404, 4.231)
0.293, 17.9%
0.113
0.230, 0.165
High
Alpelisib
1 [19]
1.300 (0.647, 2.612)
Buparlisib
4 [22-24, 26]
2.868 (1.507, 5.459)
0.790, 0.0%
Taselisib
1 [21]
8.352 (1.033, 67.540)
Pictilisib
1 [25]
14.455 (0.812, 257.300)
Nausea (all AE)
Overall
6 [19, 21-24, 26]
2.241 (1.896, 2.649)
0.930, 0.0%
0.277
1.000, 0.726
High
Alpelisib
1 [19]
2.819 (1.960, 4.053)
Buparlisib
4 [22-24, 26]
2.120 (1.739, 2.585)
0.930, 0.0%
Taselisib
1 [21]
1.991 (1.084, 3.659
High
Nausea (3-5 AE)
Overall
6 [19, 21-23, 25-26]
1.405 (0.604, 3.269)
0.288, 19.3%
0.146
0.707, 0.489
Alpelisib
1 [19]
7.227 (0.883, 59.126)
Buparlisib
3 [22-23, 26]
0.915 (0.425, 1.972)
0.527, 0.0%
Taselisib
1 [21]
3.018 (0.122, 74.618)
Pictilisib
1 [25]
6.434 (0.327, 126.509)
Vomiting (all AE)
Overall
4 [19, 23-24, 26]
1.739 (0.943, 3.206)
0.003,78.8%&
0.066
0.734, 0.767
Moderate
Alpelisib
1 [19]
3.441 (2.151, 5.503)
—
Buparlisib
3 [23-24, 26]
1.228 (0.929, 1.624)
0.791, 0.0%
Vomiting (3-5 AE)
Overall
4 [19, 23, 25-26]
1.636 (0.789, 3.392)
0.897, 0.0%
0.657
0.734, 0.811
High
Alpelisib
1 [19]
2.028 (0.183, 22.496)
Buparlisib
2 [23, 26]
1.497 (0.665, 3.372)
0.565, 0.0%
Pictilisib
1 [25]
2.721 (0.277, 26.704)
Decreased appetite (all AE)
Overall
4 [19, 22-23, 26]
3.541 (2.731, 4.590)
0.349, 8.7%
0.280
0.308, 0.456
High
Alpelisib
1 [19]
4.728 (3.016, 7.411)
Buparlisib
3 [22-23, 26]
3.180 (2.403, 4.208)
0.568, 0.0%
Decreased appetite (3-5 AE)
Overall
4 [19, 22-23, 26]
3.207 (1.044, 9.853)
0.652, 0.0%
0.714
0.308, 0.144
High
Alpelisib
1 [19]
2.028 (0.183, 22.496)
Buparlisib
3 [22-23, 26]
3.643 (1.024, 12.958)
0.486, 0.0%
Stomatitis (all AE)
Overall
6 [19, 21-24, 26]
3.741 (2.924, 4.785)
0.696, 0.0%
0.333
1.000, 0.735
High
Alpelisib
1 [19]
4.888 (2.825, 8.458)
Buparlisib
4 [22-24, 26]
3.415 (2.564, 4.548)
0.710, 0.0%
Taselisib
1 [21]
4.660 (1.713, 12.67)
Stomatitis (3-5 AE)
Overall
6 [19, 21-24, 26]
4.482 (1.767, 11.371)
0.967, 0.0%
0.834
0.452, 0.081
Moderate
Alpelisib
1 [19]
15.541 (0.883, 273.393)
Buparlisib
4 [22-24, 26]
3.973 (1.412, 11.175)
0.994, 0.0%
Taselisib
1 [21]
3.018 (0.122, 74.618)
General and skin disorders
Fatigue (all AE)
Overall
6 [19, 21-24, 26]
1.234 (1.018, 1.496)
0.318, 14.9%
0.385
0.260, 0.097
Moderate
Alpelisib
1 [19]
1.559 (1.035, 2.349)
Buparlisib
4 [22-24, 26]
1.272 (1.041, 1.554)
0.655, 0.0%
Taselisib
1 [21]
0.782 (0.464, 1.316)
Fatigue (3-5 AE)
Overall
7 [19, 22-26]
2.791 (1.689, 4.613)
0.608, 0.0%
0.341
0.707, 0.805
High
Alpelisib
1 [19]
3.455 (0.941, 12.688)
Buparlisib
4 [22-24, 26]
2.526 (1.451, 4.398)
0.553, 0.0%
Pictilisib
1 [25]
14.455 (0.812, 257.300)
Rash (all AE)
Overall
6 [19, 21-24, 26]
4.403 (2.587, 7.492)
0.002, 74.2%&
0.953
0.707, 0.522
Moderate
Alpelisib
1 [19]
8.766 (5.072, 15.148)
Buparlisib
4 [22-24, 26]
3.902 (1.964, 7.753)
0.004, 77.7%&
Taselisib
1 [21]
2.735 (0.953, 7.853)
Rash (3-5 AE)
Overall
6 [19, 21-24, 26]
14.634 (6.090, 35.160)
0.688, 0.0%
0.955
1.000, 0.645
High
Alpelisib
1 [19]
31.281 (4.226, 231.549)
Buparlisib
4 [22-24, 26]
13.499 (4.204,43.349)
0.362, 6.2%
Taselisib
1 [21]
7.128 (0.365, 139.069)
Metabolism and nervous system disorders
Hyperglycaemia (all AE)
Overall
4 [19, 21-22, 24]
7.720 (3.035, 19.637)
0.000, 88.4%&
0.406
0.734, 0.767
Moderate
Alpelisib
1 [19]
16.255 (10.273, 25.719)
Buparlisib
2 [22, 26]
9.603 (2.823, 32.666)
0.032, 78.3%&
Taselisib
1 [21]
2.168 (1.045, 4.495)
Hyperglycaemia (3-5 AE)
Overall
5 [19, 21-22, 25-26]
30.844 (11.114, 85.602)
0.359, 8.3%
0.474
0.086, 0.064
Moderate
Alpelisib
1 [19]
82.333 (20.070, 337.758)
Buparlisib
2 [22, 26]
24.869 (4.825, 128.190)
0.680, 0.0%
Taselisib
1 [21]
5.060 (0.241, 106.208)
Pictilisib
1 [25]
8.368 (0.443, 157.925)
Headache (all AE)
Overall
4 [21-23, 26]
0.981 (0.768, 1.252)
0.842, 0.0%
0.774
0.308, 0.053
High
Buparlisib
1 [21]
0.995 (0.768, 1.291)
0.681, 0.0%
Taselisib
3 [22, 23, 26]
0.877 (0.431, 1.785)
0.831, 0.0%
Headache (3-5 AE)
Overall
4 [21-23, 26]
0.838 (0.522, 1.346)
0.842, 0.0%
0.881
0.734, 0.665
High
Buparlisib
1 [21]
0.808 (0.427, 1.527)
0.669, 0.0%
Taselisib
3 [22-23, 26]
0.877 (0.431,1.785)
Significant differences, &Substantial heterogeneity, #Source of heterogeneity.
