Table 2.

Subgroup analyses for the incidence and risk of all-grade ILD/pneumonitis related to CDK4/6 inhibitors.

Group/Subgroup	No. of studies	ILD/pneumonitis
		No. of patients		Peto Odds Ratio	95% CI	I [2] (%),	P value
		Treatment	Control			χ [2] p value
Overall	12	131/8407 (1.6%)	50/7349 (0.7%)	2.12	1.57, 2.86	0%, 0.98	<0.00001
Phase							0.70
II	3	10/325 (3.1%)	3/184 (1.6%)	1.70	0.53, 5.44	0%, 0.85	0.37
III	9	121/8082 (1.5%)	47/7165 (0.7%)	2.16	1.58, 2.94	0%, 0.92	< 0.00001
Cancer type							0.19
BC	9	123/7972 (1.5%)	45/7062 (0.6%)	2.24	1.65, 3.06	0%, 0.98	< 0.00001
Other	3	8/435 (1.8%)	5/287 (1.7%)	1.02	0.33, 3.16	0%, 0.93	0.97
CDK4/6 inhibitor assignation							0.24
monotherapy	2	7/371 (1.9%)	4/227 (1.8%)	1.04	0.30, 3.58	0%, 0.71	0.95
In combination withother chemotherapy	10	124/8036 (1.5%)	46/7122 (0.6%)	2.22	1.63, 3.02	0%, 0.99	< 0.00001
CDK4/6 inhibitor							0.92
Palbociclib	3	16/3348 (0.5%)	6/3212 (0.2%)	2.41	1.04, 5.59	0%, 0.73	0.04
Abemaciclib	7	108/4397 (2.5%)	42/3639 (1.2%)	2.10	1.51, 2.92	0%, 0.88	< 0.00001
Ribociclib	2	7/662 (1.1%)	2/498 (0.4%)	1.77	0.44, 7.10	0%, 0.44	0.42
Control group setting							0.42
Other chemotherapy	2	9/261 (3.4%)	2/124 (1.6%)	1.93	0.54, 6.94	0%, 0.73	0.32
Endocrine therapy	8	117/7817 (1.5%)	44/6990 (0.6%)	2.24	1.63, 3.07	0%, 0.97	< 0.00001
Anti-EGFR agents	2	5/329 (1.5%)	4/235 (1.7%)	0.89	0.23, 3.39	0%, 0.97	0.87
CDK4/6 inhibitor setting							0.44
Adjuvant setting	2	89/5631 (1.6%)	38/5730 (0.7%)	2.28	1.61, 3.24	0%, 0.82	< 0.00001
Other setting	10	42/2776 (1.5%)	12/1619 (0.7%)	1.76	0.99, 3.10	0%, 0.96	0.05

Abbreviation: BC, breast cancer. Significant differences (P value < 0.05) between treatment group and control group are shown in bold.