Progression-free survival/time to progression as a potential surrogate for overall survival in HR+, HER2− metastatic breast cancer

Figures & data

Figure 1 Flow chart of articles included in the analysis.

Table 1 Subgroup analysis of correlation between median PFS/TTP and median OS

Categories	Sub-group	Sample number	Pearson’s coefficient	P-value	Spearman’s coefficient	P-value
Reference case		79	0.741	0.000	0.650	0.000
Definition of surrogate	PFS	73	0.747	0.000	0.664	0.000
	TTP	6	0.532	0.278	0.086	0.862
Age group (years)	40–59.9	52	0.749	0.000	0.646	0.000
	≥60	17	0.793	0.000	0.722	0.001
Line of therapy	First line	43	0.747	0.000	0.659	0.000
	Second line or more	26	0.673	0.000	0.534	0.002
Chemotherapy setting	Chemotherapy setting	59	0.741	0.000	0.681	0.000
	Others	20	0.790	0.000	0.646	0.021
ECOG (%)	ECOG 0>50	34	0.724	0.000	0.555	0.000
	ECOG 0<50	9	0.936	0.000	0.929	0.000
	ECOG 0>60	19	0.726	0.000	0.463	0.046
	ECOG 0<60	24	0.780	0.000	0.739	0.000
HER2− (%)	100	43	0.602	0.000	0.491	0.001
	<100	30	0.844	0.000	0.793	0.000
HR+ (%)	100	14	0.827	0.000	0.899	0.000
	<100	35	0.355	0.036	0.353	0.004
ER+ (%)	>75	16	0.801	0.000	0.551	0.027
	≤75	18	0.895	0.000	0.854	0.000
PR+ (%)	>60	12	0.765	0.004	0.413	0.183
	≤60	14	0.922	0.000	0.820	0.000
Visceral metastases (%)	>50	46	0.673	0.000	0.652	0.000
	≤50	7	0.557	0.195	0.072	0.878
Number of metastatic sites, <3 sitesa (%)	At least 60	37	0.725	0.000	0.493	0.002
Prior endocrine therapy (%)	At least 50	23	0.448	0.032	0.316	0.141
	<50	12	0.892	0.000	0.830	0.001
Prior chemotherapy (adjuvant/neoadjuvant, n) (%)	At least 75	11	0.666	0.025	0.360	0.277
	<75	32	0.812	0.000	0.755	0.000

Note:

a The results in the subgroup of <60% are not presented because there were only two observations from one RCT.

Abbreviations: ECOG, Eastern Cooperative Oncology Group; ER+, estrogen receptor positive; HER2−, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; OS, overall survival; PFS, progression-free survival; PR+, progesterone receptor positive; RCT, randomized controlled trial; TTP, time to progression.

Figure 2 Regression analysis with weighted trial size.

Note: Point size corresponds to trial size.
Abbreviations: CI, confidence interval; OS, overall survival; PFS, progression-free survival.

Figure 3 Multivariate regression analysis adding two covariates.

Note: Point size corresponds to trial size.
Abbreviations: CI, confidence interval; OS, overall survival; PFS, progression-free survival.

Table S1 Search strategy for MEDLINE

1	exp Breast Neoplasms/	250773
2	(breast adj6 cancer$).af.	246948
3	(breast adj6 neoplas$).af.	252542
4	(breast adj6 carcinoma$).af.	63807
5	(breast adj6 tumour$).af.	7401
6	(breast adj6 tumor$).af.	48416
7	1 or 2 or 3 or 4 or 5 or 6	336672
8	metasta$.mp. or exp Neoplasm Metastasis/	477568
9	7 and 8	74656
10	(“metastatic breast cancer” or “metastatic breast neoplasms”).af.	11972
11	9 or 10	74661
12	‘hormone receptor positive’.af.	2300
13	‘hormone receptor-positive’.af.	2300
14	(‘estrogen receptor-positive’ or ‘oestrogen receptor-positive’).af.	4218
15	‘progesterone receptor-positive’.af.	732
16	‘hormone sensitive’.af.	3719
17	12 or 13 or 14 or 15 or 16	10513
18	11 and 17	1955
19	exp randomized controlled trials/	111704
20	randomized controlled trial.pt.	448501
21	exp random allocation/or exp randomization/	89826
22	exp placebos/	34191
23	exp Double-Blind Method/or double-blind$.af.	180225
24	exp Multicenter Study/or multicent$.af.	279405
25	random$.ti,ab,kw,sh.	1124651
26	blind$.ti,ab,kw,sh.	263750
27	placebo$.ti,ab,kw,sh.	203823
28	parallel$.ti,ab,kw,sh.	266233
29	exp clinical trial, phase 3/	13116
30	exp clinical trial, phase 2/	29002
31	(‘phase 3’ or ‘phase 2’ or (‘phase III’ or ‘phase II’)).af.	112861
32	19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31	1752319
33	18 and 32	610
34	limit 33 to yr=”2006 -Current”	422
35	limit 34 to “review articles”	74
36	34 not 35	348
37	limit 36 to humans	297
38	remove duplicates from 37	244

Table S2 Search strategy for Embase

1	breast cancer’.af.	404912
2	exp breast tumor/	456726
3	(breast adj6 tumour*).mp	10358
4	(breast adj6 tumor*).mp	132238
5	(breast adj6 neoplas*).mp	22949
6	(breast adj6 cancer*).mp	446177
7	(breast adj6 carcinoma*).mp	95202
8	1 or 2 or 3 or 4 or 5 or 6 or 7	513111
9	metastasis/	310169
10	metasta*	697570
11	9 or 10	697570
12	8 and 11	123533
13	(‘metastatic breast neoplasms’ or ‘metastatic breast neoplasm’ or ‘metastatic breast cancer’).mp	19097
14	12 or 13	123533
15	hormone receptor positive’ OR ‘hormone receptor-positive’	3917
16	progesterone receptor-positive’ OR ‘progesterone receptor positive’	1185
17	estrogen receptor-positive’ or ‘oestrogen receptor-positive’	7549
18	hormone sensitive’	4924
19	hormone adj3 positive	5460
20	15 or 16 or 17 or 18 or 19	17999
21	14 and 20	4258
22	exp ‘randomized controlled trial’/	481221
23	randomization/	84943
24	random*.ti,ab.	1181594
25	parallel*.ti,ab	303245
26	((single or double or triple) adj3 (blind* or mask* or dummy)).ti,ab.	201720
27	double-blind’ or ‘double-blinded’	219339
28	multicenter study’ or multicent*	277968
29	blind*.ti,ab.	341487
30	placebo*.ti,ab	254042
31	(‘phase 3’ OR ‘phase 2’).ti,ab	40098
32	(‘phase iii’ OR ‘phase ii’).ti,ab	111214
33	22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32	2028041
34	21 and 33	1173
35	limit 34 to human	1094
36	limit 35 to english language	1075
37	limit 36 to yr=”2006 -Current”	898
38	limit 37 to embase	562
39	limit 38 to (article or conference abstract)	501

Table S3 Search strategy for Cochrane Library

1	exp Breast Neoplasms	9184
2	breast adj6 cancer$	21934
3	breast adj6 neoplas$	10989
4	breast adj6 carcinoma$	2112
5	breast adj6 tumour$	573
6	breast adj6 tumor$	1851
7	1 or 2 or 3 or 4 or 5 or 6	23744
8	metasta$	21265
9	Neoplasm Metastasis.sh.	2226
10	8 or 9	21265
11	7 and 10	6121
12	‘hormone receptor positive’	607
13	hormone receptor-positive’ 588	607
14	‘estrogen receptor-positive’ or ‘oestrogen receptor-positive’ 654	522
15	‘progesterone receptor-positive’ 250	109
16	hormone sensitive 986	210
17	12 or 13 or 14 or 15 or 16 2325	1318
18	11 and 17	453
19	limit 18 to yr=”2006 -Current”	329
20	limit 19 to english language	284
21	limit 20 to humans	278
22	remove duplicates from 21	272