Overall survival in all cancer patients		ESA arm			Control arm			ESA versus control
Subgroups	Patients	events	sample	%	events	sample	%	HR	95% CI	P value*
Patient level characteristics
Hb at baseline
Hb at baseline (continuous)										0.75
Hb at baseline (cat 1)										0.63
Hb ≤ 8 g/dL	791	176	448	39%	147	343	43%	1.08	0.87‐1.35
Hb 8‐≤10 g/dL	3930	725	2222	33%	672	1708	39%	1.02	0.92‐1.14
Hb 10‐≤12 g/dL	5004	967	2851	34%	777	2153	36%	1.11	1.01‐1.22
Hb 12‐≤14 g/dL	2843	566	1433	39%	553	1410	39%	1.06	0.95‐1.20
Hb >14 g/dL	839	155	428	36%	155	411	38%	0.94	0.75‐1.18
Unknown	526	54	252	21%	46	274	17%	1.22	0.82‐1.82
Hb at baseline (cat 2)										0.83
Hb ≤ 8 g/dL	791	176	448	39%	147	343	43%	1.08	0.87‐1.35
Hb 8‐≤9 g/dL	1319	256	742	35%	252	577	44%	1.05	0.88‐1.25
Hb 9‐≤10 g/dL	2611	469	1480	32%	420	1131	37%	1.02	0.89‐1.16
Hb 10‐≤11 g/dL	2927	542	1699	32%	414	1228	34%	1.16	1.02‐1.32
Hb 11‐≤12 g/dL	2077	425	1152	37%	363	925	39%	1.06	0.92‐1.22
Hb 12‐≤13 g/dL	1739	377	873	43%	371	866	43%	1.04	0.90‐1.20
Hb 13‐≤14 g/dL	1104	189	560	34%	182	544	33%	1.12	0.91‐1.37
Hb >14 g/dL	839	155	428	36%	155	411	38%	0.94	0.75‐1.18
Unknown	526	54	252	21%	46	274	17%	1.23	0.83‐1.83
Malignancy type
Tumour (cat. 1)										0.23
Haematological malignancies	2403	378	1400	27%	286	1003	29%	1.19	1.02‐1.39
Solid tumours	10795	2103	5848	36%	1916	4947	39%	1.04	0.98‐1.11
Other	693	158	369	43%	145	324	45%	0.99	0.82‐1.20
Missing / unknown	42	4	17	24%	3	25	12%	2.14	0.48‐9.62
Tumour (cat. 2)										0.21
Haematological malignancies	2403	378	1400	27%	286	1003	29%	1.18	1.01‐1.38
Breast cancer	4302	563	2245	25%	481	2057	23%	1.13	1.00‐1.28
Head and neck cancer	868	235	443	53%	208	425	49%	1.14	0.91‐1.42
Lung cancer	3076	986	1618	61%	975	1458	67%	0.98	0.89‐1.07
Gastrointestinal cancer	708	124	434	29%	103	274	38%	0.89	0.68‐1.16
Gynaecological cancer	1399	115	842	14%	87	557	16%	1.13	0.85‐1.50
Genitourinal cancer	442	80	266	30%	62	176	35%	1.24	0.89‐1.73
Other	693	158	369	43%	145	324	45%	0.99	0.82‐1.20
Missing / unknown	42	4	17	24%	3	25	12%	2.12	0.47‐9.50
Sex
Male	5136	1323	2854	46%	1193	2282	52%	1.01	0.94‐1.10	0.15
Female	8797	1320	4780	28%	1157	4017	29%	1.10	1.02‐1.19
Age
Age continuous										0.38
Age categorical										0.26
< 18 years	123	0	55	0%	1	68	1%	Not estimable	Not estimable
≥18‐35 years	346	37	191	19%	27	155	17%	0.89	0.54‐1.46
≥35‐45 years	1343	196	745	26%	147	598	25%	1.02	0.82‐1.26
≥45‐55 years	3010	536	1614	33%	439	1396	31%	1.16	1.03‐1.32
≥55‐65 years	4193	818	2237	37%	793	1956	41%	1.01	0.91‐1.11
≥65‐75 years	3517	780	1970	40%	711	1547	46%	1.04	0.94‐1.15
≥75 years	1389	276	816	34%	231	573	40%	1.20	1.00‐1.43
Missing	12	0	6	0%	1	6	17%	Not estimable	Not estimable
Hct levels at baseline
Hct continuous										0.90
Hct categorical										0.03
≤ 23.5%	390	82	210	39%	55	180	31%	1.66	1.18‐2.34
23.5‐≤ 29.4%	2788	476	1567	30%	479	1221	39%	0.94	0.83‐1.07
29.4‐≤ 35.3%	4615	945	2692	35%	732	1923	38%	1.10	0.99‐1.21
35.3‐≤ 41.2%	2458	579	1258	46%	558	1200	47%	1.07	0.95‐1.21
> 41.2%	785	169	414	41%	165	371	44%	1.02	0.82‐1.26
Missing / unknown	2897	392	1493	26%	361	1404	26%	1.08	0.93‐1.24
Serum Epo at baseline
Serum Epo continuous										0.14
Serum Epo categorical										0.81
< 25 mU/ml	1497	341	876	39%	309	621	50%	0.97	0.84‐1.14
25‐100 mU/ml	2908	586	1643	36%	548	1265	43%	1.02	0.90‐1.14
100‐200 mU/ml	740	187	451	41%	130	289	45%	1.10	0.88‐1.38
200‐500 mU/ml	325	60	190	32%	51	135	38%	1.18	0.81‐1.72
> 500 mU/ml	181	31	103	30%	22	78	28%	1.08	0.63‐1.88
Unknown	8282	1438	4371	33%	1290	3911	33%	1.09	1.01‐1.17
Performance score
ECOG categorical										0.41
ECOG 0	3392	351	1808	19%	341	1584	22%	1.06	0.91‐1.23
ECOG 1	4900	984	2779	35%	814	2121	38%	1.09	0.99‐1.20
ECOG 2	1678	490	933	53%	433	745	58%	1.01	0.89‐1.15
ECOG 3	139	48	77	62%	35	62	56%	1.18	0.76‐1.82
ECOG 4	3	2	2	100%	0	1	0%	Not estimable	Not estimable
ECOG missing	3821	768	2035	38%	727	1786	41%	1.02	0.93‐1.14
ECOG dichotomous										0.50
ECOG 0, 1, 2	10083	1847	5578	33%	1604	4505	36%	1.08	1.01‐1.15
ECOG 3, 4	142	50	79	63%	35	63	56%	1.25	0.81‐1.93
ECOG missing	3708	746	1977	38%	711	1731	41%	1.02	0.92‐1.13
Body mass index
≤ 19 kg/m²	865	187	424	44%	195	441	44%	0.95	0.78‐1.17	0.72
19‐≤ 25 kg/m²	5487	1098	2964	37%	945	2523	37%	1.06	0.97‐1.15
25‐≤ 30 kg/m²	3443	642	1864	34%	543	1579	34%	1.09	0.97‐1.22
> 30 kg/m²	1650	250	867	29%	224	783	29%	1.03	0.86‐1.24
Missing	2488	466	1515	31%	443	973	46%	1.10	0.97‐1.26
History of thromboembolic events
Yes	561	128	318	40%	107	243	44%	1.03	0.80‐1.33	0.90
No	9059	1720	5044	34%	1509	4015	38%	1.05	0.98‐1.12
Missing / not reported	4313	795	2272	35%	734	2041	36%	1.08	0.98‐1.20
History of cardiovascular events
Yes	3593	758	2002	38%	648	1591	41%	1.07	0.96‐1.19	0.69
No	6729	1141	3700	31%	1010	3029	33%	1.04	0.96‐1.13
Missing / not reported	3611	744	1932	39%	692	1679	41%	1.07	0.97‐1.19
History of hypertension
Yes	2093	420	1219	34%	373	874	43%	1.01	0.88‐1.16	0.57
No	7527	1428	4143	34%	1243	3384	37%	1.06	0.98‐1.14
Missing / not reported	4313	795	2272	35%	734	2041	36%	1.08	0.98‐1.20
History of diabetes mellitus
Yes	709	163	372	44%	158	337	47%	1.05	0.84‐1.31	0.94
No	7316	1456	3927	37%	1250	3389	37%	1.06	0.98‐1.14
Missing / not reported	5908	1024	3335	31%	942	2573	37%	1.06	0.97‐1.16
Geographical region
Northern America	3569	490	2004	24%	470	1565	30%	1.11	0.98‐1.27	0.90
Northern, Western & Southern Europe	7440	1529	4030	38%	1322	3410	39%	1.05	0.98‐1.13
Eastern Europe	1955	514	1030	50%	469	925	51%	1.03	0.91‐1.17
Australia & New Zealand	342	40	216	19%	28	126	22%	1.08	0.66‐1.75
Other	226	48	123	39%	46	103	45%	0.95	0.63‐1.43
Missing / not reported	401	22	231	10%	15	170	9%	1.47	0.75‐2.89
Tumour stage
Metastatic / advanced	8113	1918	4482	43%	1698	3631	47%	1.05	0.98‐1.12	0.86
Not metastatic / not advanced	4039	420	2116	20%	408	1923	21%	1.06	0.93‐1.22
Missing / not reported	1781	305	1036	29%	244	745	33%	1.04	0.87‐1.23
Planned Hb ceiling
Planned Hb ceiling (cat 1)										0.40
≤Hb 13.0 g/dL	3043	437	1624	27%	399	1419	28%	1.09	0.95‐1.25
Hb 13.0 ‐ ≤15.0 g/dL	10193	2019	5631	36%	1782	4562	39%	1.04	0.97‐1.11
Hb >15.0 g/dL	494	159	259	61%	152	235	65%	1.21	0.97‐1.51
Other	203	28	120	23%	17	83	20%	1.13	0.61‐2.07
Planned Hb ceiling (cat 2)										0.60
≤Hb 13.0 g/dL	3043	437	1624	27%	399	1419	28%	1.09	0.95‐1.25
Hb 13.0 – ≤14.0 g/dL	6816	1142	3733	31%	1013	3083	33%	1.03	0.95‐1.13
Hb 14.0 – ≤15.0 g/dL	3377	877	1898	46%	769	1479	52%	1.05	0.95‐1.15
>Hb 15.0 g/dL	494	159	259	61%	152	235	65%	1.21	0.97‐1.51
Other	203	28	120	23%	17	83	20%	1.13	0.61‐2.07
Study level characteristics
Treatment population
Treatment population
Chemotherapy	10441	1888	5676	33%	1667	4765	35%	1.04	0.97‐1.11	0.11
Radiochemotherapy	737	204	368	55%	211	369	57%	0.91	0.75‐1.10
Radiotherapy	799	220	408	54%	196	391	50%	1.17	0.96‐1.42
Mixed	266	17	175	10%	7	91	8%	1.53	0.63‐3.69
None	1690	314	1007	31%	269	683	39%	1.22	1.04‐1.44
Treatment population
Chemotherapy	10441	1888	5676	33%	1667	4765	35%	1.04	0.97‐1.11	0.25
Radiotherapy / radiochemotherapy	1536	424	776	55%	407	760	54%	1.03	0.90‐1.18
Mixed	266	17	175	10%	7	91	8%	1.53	0.63‐3.69
None	1690	314	1007	31%	269	683	39%	1.22	1.04‐1.44
Iron supplementation
Fixed iron supplementation	2589	468	1293	36%	467	1296	36%	1.00	0.87‐1.13	0.48
Iron supplementation as needed	11120	2075	6232	33%	1782	4888	36%	1.07	1.00‐1.14
Other	224	100	109	92%	101	115	88%	1.17	0.89‐1.55
Planned ESA treatment duration
Up to 8 weeks	415	55	256	21%	47	159	30%	1.09	0.74‐1.62	0.74
9‐16 weeks	4800	667	2738	24%	644	2062	31%	1.02	0.91‐1.14
> 17 weeks	3269	816	1701	48%	747	1568	48%	1.11	1.00‐1.22
Until end of chemo‐ or radiotherapy	5449	1105	2939	38%	912	2510	36%	1.05	0.96‐1.14
Planned weekly ESA dosage
< 100 µg Darbepoetin or < 40000 IU Epoetin	4197	832	2297	36%	669	1900	35%	1.04	0.94‐1.15	0.88
= 100 µg Darbepoetin or = 40000 IU Epoetin	3081	557	1545	36%	536	1536	35%	1.08	0.96‐1.22
> 100 µg Darbepoetin or > 40000 IU Epoetin	3845	876	2076	42%	808	1769	46%	1.08	0.98‐1.19
Other	2810	378	1716	22%	337	1094	31%	1.02	0.88‐1.18
Planned frequency of ESA application
Three times per week or more frequent	6131	1067	3458	31%	840	2673	31%	1.07	0.98‐1.18	0.07
Once per week	3948	911	1972	46%	886	1976	45%	1.06	0.97‐1.17
Every second week or less frequent	3036	347	1795	19%	286	1241	23%	1.20	1.02‐1.40
Other	818	318	409	78%	338	409	83%	0.90	0.77‐1.05
Placebo controlled trial
Yes	7657	1578	4211	37%	1403	3446	41%	1.09	1.01‐1.17	0.29
No	6276	1065	3423	31%	947	2853	33%	1.02	0.93‐1.12
Randomisation
Adequate	3882	739	2047	36%	636	1835	35%	1.07	0.96‐1.19	0.80
Unclear	10051	1904	5587	34%	1714	4464	38%	1.05	0.99‐1.13
Concealment of allocation
Adequate	10595	2176	5839	37%	1901	4756	40%	1.07	1.00‐1.14	0.49
Unclear	3338	467	1795	26%	449	1543	29%	1.02	0.89‐1.16
Endpoint survival
Primary endpoint	3116	732	1547	47%	715	1569	46%	1.02	0.92‐1.13	0.39
Secondary endpoint	4313	1164	2282	51%	985	2031	48%	1.04	0.96‐1.14
Safety /adverse events	6504	747	3805	20%	650	2699	24%	1.13	1.01‐1.25
Designed for long‐term follow‐up
Yes	8974	2213	4619	48%	1972	4355	45%	1.06	1.00‐1.13	0.64
No	4959	430	3015	14%	378	1944	19%	1.03	0.89‐1.18
Year of last patient randomized
1990‐1994	1447	100	890	11%	70	557	13%	0.96	0.70‐1.31	0.13
1995‐1999	1725	312	1001	31%	224	724	31%	0.97	0.81‐1.16
2000‐2004	7620	1453	4105	35%	1296	3515	37%	1.13	1.04‐1.21
2005‐2006	3141	778	1638	47%	760	1503	51%	0.99	0.89‐1.09
Source of data
Manufacturer	12229	2434	6789	36%	2151	5440	40%	1.06	1.00‐1.13	0.57
Clinical study group	1704	209	845	25%	199	859	23%	1.00	0.83‐1.22
*P value for likelihood‐ratio test (test for interaction), patients with missing data are excluded from this test, analysis based on one‐stage Cox fixed‐effects model stratified by study ESA= erythropoiesis‐stimulating agents