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 2

Efficacy of included RCTs of PI3K inhibitors in treatment of breast cancer.

Outcomes	PIK3CA mutation status	Included RCTs	OR (95% CI)	,	Meta-regression	Publication bias	Certainty of evidence
Objective response rate (ORR)	Overall	7 [20, 21-24, 26-27]	1.539 (1.074, 2.204)	0.015, 54.6%^&		0.683, 0.000	Low
	Mutated	5 [20-21, 23-24, 26]	1.952 (1.012, 3.766)	0.030, 62.6%^&	0.306	0.624, 0.715	Moderate
	Alpelisib	1[20]	2.474 (1.410, 4.343)		0.785
	Buparlisib	3 [23-24, 26]	1.481 (0.270, 8.112)	0.009, 78.6%^&		1.000, 0.996	Moderate
	Taselisib	1 [21]	2.093 (1.094, 4.002)
	Wild-type	3 [21, 23-24]	1.252 (0.833, 1.882)	0.630, 0.0%		0.602, 0.251	Moderate
	Total	3 [22, 26-27]	1.303 (0.621, 2.734)	0.075, 61.3%^&		0.117, 0.029	Low
Progression-free survival (PFS)
6m-PFS	Overall	7 [19-20, 22-23, 25-27]	1.189 (0.965, 1.465)	0.080, 37.1%	0.292	0.152, 0.000	Moderate
	Mutated	6 [20, 22-23, 25-27]	1.519 (1.144, 2.018)	0.841, 0.0%		0.188, 0.761	High
	Alpelisib	1 [20]	1.549 (1.010, 2.376)		0.678
	Buparlisib	3 [22, 23, 26]	1.427 (0.924, 2.205)	0.396, 0.0%		0.602, 0.859	Moderate
	Pictilisib	2 [25, 27]	1.736 (0.802, 3.761)	0.935, 0.0%		0.371, -	Moderate
	Wild-type	3 [20, 22, 26]	0.938 (0.575, 1.529)	0.132, 50.7%^&		0.117, 0.106	Low
	Total	4 [19, 23, 25, 27]	1.134 (0.806, 1.596)	0.088, 50.6%^&		1.000, 0.354	Moderate
1y-PFS	Overall	6 [19, 20, 22-23, 25-26]	1.188 (0.880, 1.603)	0.095, 36.9%	0.840	0.353, 0.000	Moderate
	Mutated	5 [20, 22-23, 25-26]	1.392 (0.972, 1.992)	0.471, 0.0%		1.000, 0.686	High
	Wild-type	3 [20, 22, 26]	0.931 (0.278, 3.115)	0.163, 44.8%		0.117, 0.084	Moderate
	Total	3 [19, 23, 25]	1.210 (0.756, 1.938)	0.048, 62.0%^&		0.497, 0.384	Low
1.5y-PFS	Overall	6 [19, 20, 23-24, 26-27]	1.506 (1.071, 2.119)	0.892, 0.0%	0.725	0.173, 0.021	Moderate
	Mutated	5 [20, 23-24, 26-27]	1.577 (0.907, 2.740)	0.865, 0.0%		0.624, 0.693	High
	Wild-type	2 [23, 26]	1.995 (0.632, 6.294)	0.755, 0.0%		0.317, -	Moderate
	Total	3 [19, 24, 27]	1.368 (0.829, 2.258)	0.354, 7.8%		0.042, 0.079	Moderate
2y-PFS	Overall	4 [19-20, 24, 26]	1.716 (0.758, 3.885)	0.934, 0.0%	0.986	0.564, -	High
	Mutated	2 [20, 26]	1.840 (0.491, 6.898)	0.818, 0.0%		0.317, -	Moderate
	Wild-type	2 [24, 26]	1.360 (0.219, 0.435)	0.733, 0.0%		0.317, -	Moderate
	Total	1 [19]	1.771 (0.475, 6.603)	0.303, 5.8%		0.317, -	Moderate
PFS from HR data	Overall	7 [19-20, 22-23, 25-27]	-0.271 (-0.369, -0.173)	0.342, 10.3%	0.315	0.126, 0.000	Moderate
	Mutated	7 [19-20, 22-23, 25-27]	-0.346 (-0.525, -0.168)	0.235, 25.4%		0.293, 0.586	High
	Alpelisib	2 [19-20]	-0.431 (-0.658, -0.203)	1.000, 0.0%	0.398	0.371, -
	Buparlisib	3 [22, 23, 26]	-0.324 (-0.526, -0.123)	0.046, 67.6%^&		0.602, 0.602	Moderate
	Pictilisib	2 [25, 27]	-0.171 (-0.607, 0.266)	0.415, 0.0%		0.371, -
	Wild-type	3 [20, 22, 26]	-0.168 (-0.413, 0.077)	0.306, 15.5%		0.117, 0.003	Low
	Total	3 [23, 25, 27]	-0.238 (-0.364, -0.112)	0.647, 0.0%		0.602, 0.678	Low

Significant differences, ^&Substantial heterogeneity.