Table 2. Meta analysis summary of adverse events.

AE	Number of studies	Number of evaluable patients	Number of patients with AE	Random effects toxicity rate (%)	Random effects 95% confidence interval	Heterogeneity p-value	I2
Any AE	10	1450	1435	98.4	96.9–99.2	0.12	36.5
Any Serious AE	9	1198	430	34.5	28.1–41.6	< 0.001	82.6
Any Grade 3/4 AE	8	1147	751	64.0	47.1–78.0	< 0.001	96.1
Diarrhea	15	2005	1133	54.4	40.5–67.6	< 0.001	96.5
Diarrhea 3/4	15	2005	49	2.6	1.6–4.2	0.013	50.7
Nausea	15	2005	1087	51.5	29.5–63.3	< 0.001	95.8
Nausea 3/4	15	2005	53	2.5	1.6–4.1	0.003	56.9
Vomiting	15	2005	852	38.3	29.1–48.3	< 0.001	94.3
Vomiting 3/4	15	2005	51	2.7	1.8–4.2	0.025	46.4
Constipation	14	1973	618	31.0	26.5–35.8	< 0.001	79.7
Constipation 3/4	14	1973	12	1.2	0.7–1.9	0.68	0.0
Fatigue	14	1901	533	27.2	22.9–31.9	< 0.001	78.8
Fatigue 3/4	14	1901	54	3.2	2.0–5.0	0.004	57.7
ALT	12	1552	502	28.2	19.8–38.3	< 0.001	93.5
ALT 3/4	12	1552	239	11.1	7.1–16.9	< 0.001	89.4
AST	13	1662	447	24.8	18.3–32.5	< 0.001	90.7
AST 3/4	13	1662	125	6.8	4.6–9.9	< 0.001	74.5
QTc	5	477	40	8.6	4.9–14.8	0.04	60.1
QTc 3/4	11	1558	28	2.1	1.2–3.6	0.061	43.4
ILD	9	1255	26	2.2	1.2–4.0	0.04	50.5
ILD 3/4	10	1346	17	1.9	1.2–3.0	0.54	0

Abbreviations: AE = Adverse Event; ALT = Alanine Aminotransferase; AST = Aspartate Aminotransferase; ILD = Interstial Lung Disease.

^*Meta-analyses were conducted using one-sample proportions to obtain random effects, estimates of toxicity rates and 95% confidence intervals. Heterogeneity was assessed by the Q chi square statistic. p ≤ 0.05 was considered statistically significant.

The percent of total variance for study heterogeneity was estimated using the I squared (I²) statistic. Analyses were conducted using Comprehensive Meta-Analysis software package (Comprehensive Meta-Analysis, Version 3.3.070, 2014, Biostatic; Englewood NJ).