Mortality in all cancer patients during the  active study period		ESA arm			Control arm			ESA versus control
	Patients	events	sample	%	events	sample	%	HR	95% CI	P value*
Patient level characteristics
Hb at baseline (continuous)										0.82
Hb at baseline (cat. 1)										0.75
Hb ≤ 8 g/dL	791	90	448	20%	58	343	17%	1.28	0.92‐1.78
Hb 8‐≤ 10 g/dL	3930	292	2222	13%	239	1708	14%	1.08	0.91‐1.28
Hb 10‐≤ 12 g/dL	5004	300	2851	11%	220	2153	10%	1.22	1.03‐1.46
Hb 12‐≤ 14 g/dL	2843	141	1433	10%	114	1410	8%	1.28	1.00‐1.64
Hb > 14 g/dL	839	37	428	9%	30	411	7%	1.06	0.66‐1.72
Unknown	526	5	252	2%	4	274	1%	0.91	0.24‐3.40
Hb at baseline (cat. 2)										0.79
Hb ≤ 8 g/dL	791	90	448	20%	58	343	17%	1.28	0.92‐1.79
Hb 8‐≤ 9 g/dL	1319	117	742	16%	101	577	18%	1.05	0.81‐1.38
Hb 9‐≤ 10 g/dL	2611	175	1480	12%	138	1131	12%	1.11	0.89‐1.39
Hb 10‐≤ 11 g/dL	2927	188	1699	11%	121	1228	10%	1.34	1.07‐1.69
Hb 11‐≤ 12 g/dL	2077	112	1152	10%	99	925	11%	1.07	0.82‐1.41
Hb 12‐≤ 13 g/dL	1739	92	873	11%	80	866	9%	1.22	0.90‐1.64
Hb 13‐≤ 14 g/dL	1104	49	560	9%	34	544	6%	1.45	0.93‐2.24
Hb >14 g/dL	839	37	428	9%	30	411	7%	1.06	0.65‐1.72
Unknown	526	5	252	2%	4	274	1%	0.92	0.25‐3.44
Malignancy type
Tumour (cat. 1)										0.16
Haematological malignancies	2403	128	1400	9%	79	1003	8%	1.20	0.91‐1.60
Solid tumours	10795	684	5848	12%	532	4947	11%	1.20	1.07‐1.35
Other	693	49	369	13%	51	324	16%	0.81	0.54‐1.20
Missing / unknown	42	4	17	24%	3	25	12%	1.99	0.44‐8.94
Tumour (cat. 2)										0.47
Haematological malignancies	2403	128	1400	9%	79	1003	8%	1.19	0.90‐1.59
Breast cancer	4302	224	2245	10%	164	2057	8%	1.34	1.10‐1.65
Head and neck cancer	868	23	443	5%	20	425	5%	1.13	0.62‐2.07
Lung cancer	3076	292	1618	18%	243	1458	17%	1.17	0.99‐1.39
Gastrointestinal cancer	708	61	434	14%	44	274	16%	0.96	0.65‐1.42
Gynaecological cancer	1399	40	842	5%	27	557	5%	1.18	0.72‐1.94
Genitourinary cancer	442	44	266	17%	34	176	19%	1.02	0.65‐1.60
Other	693	49	369	13%	51	324	16%	0.81	0.54‐1.20
Missing / unknown	42	4	17	24%	3	25	12%	1.96	0.44‐8.79
Sex
Male	5136	419	2854	15%	309	2282	14%	1.15	0.99‐1.34	0.86
Female	8797	446	4780	9%	356	4017	9%	1.17	1.02‐1.35
Age
Age continuous										0.87
Age categorical										0.50
< 18 years	123	0	55	0%	1	68	1%	Not estimable	Not estimable
≥18‐35 years	346	11	191	6%	9	155	6%	0.83	0.34‐2.01
≥35‐45 years	1343	57	745	8%	34	598	6%	1.36	0.89‐2.08
≥45‐55 years	3010	162	1614	10%	111	1396	8%	1.34	1.05‐1.71
≥55‐65 years	4193	256	2237	11%	222	1956	11%	1.07	0.89‐1.28
≥65‐75 years	3517	271	1970	14%	210	1547	14%	1.16	0.97‐1.39
≥75 years	1389	108	816	13%	77	573	13%	1.27	0.94‐1.70
Missing	12	0	6	0%	1	6	17%	Not estimable	Not estimable
Hct levels at baseline
Hct continuous										0.57
Hct categorical										0.01
≤23.5%	390	55	210	26%	24	180	13%	2.19	1.35‐3.55
23.5‐≤ 29.4%	2788	199	1567	13%	191	1221	16%	0.96	0.78‐1.17
29.4‐≤ 35.3%	4615	321	2692	12%	223	1923	12%	1.17	0.99‐1.39
35.3‐≤ 41.2%	2458	176	1258	14%	130	1200	11%	1.41	1.12‐1.76
> 41.2%	785	48	414	12%	40	371	11%	1.12	0.73‐1.70
Missing	2897	66	1493	4%	57	1404	4%	1.09	0.76‐1.55
Serum Epo at baseline
Serum Epo continuous										0.21
Serum Epo categorical										0.54
<25 mU/ml	1497	95	876	11%	58	621	9%	1.33	0.96‐1.85
25‐<100 mU/ml	2908	195	1643	12%	171	1265	14%	0.98	0.80‐1.21
100‐<200 mU/ml	740	73	451	16%	47	289	16%	1.08	0.75‐1.57
200‐<500 mU/ml	325	29	190	15%	19	135	14%	1.29	0.72‐2.31
> 500 mU/ml	181	21	103	20%	10	78	13%	1.26	0.59‐2.69
Unknown	8282	452	4371	10%	360	3911	9%	1.23	1.07‐1.41
Performance score
ECOG categorical										0.63
ECOG 0	3392	86	1808	5%	76	1584	5%	1.15	0.85‐1.57
ECOG 1	4900	327	2779	12%	250	2121	12%	1.14	0.97‐1.35
ECOG 2	1678	241	933	26%	178	745	24%	1.21	1.00‐1.47
ECOG 3	139	26	77	34%	18	62	29%	1.30	0.71‐2.39
ECOG 4	3	1	2	50%	0	1	0%	Not estimable	Not estimable
ECOG missing	3821	184	2035	9%	143	1786	8%	1.12	0.90‐1.39
ECOG dichotomous										0.56
ECOG 0, 1, 2	10083	655	5578	12%	505	4505	11%	1.18	1.05‐1.33
ECOG 3, 4	142	27	79	34%	18	63	29%	1.42	0.78‐2.59
ECOG missing	3708	183	1977	9%	142	1731	8%	1.12	0.89‐1.39
Body mass index
≤ 19 kg/m²	865	76	424	18%	73	441	17%	1.00	0.73‐1.39	0.72
19‐ ≤25 kg/m²	5487	374	2964	13%	277	2523	11%	1.21	1.04‐1.42
25‐≤ 30 kg/m²	3443	193	1864	10%	144	1579	9%	1.14	0.92‐1.42
> 30 kg/m²	1650	74	867	9%	56	783	7%	1.26	0.89‐1.79
Missing	2488	148	1515	10%	115	973	12%	1.22	0.95‐1.57
History of thromboembolic events
Yes	561	40	318	13%	42	243	17%	0.80	0.52‐1.23	0.06
No	9059	637	5044	13%	474	4015	12%	1.23	1.09‐1.39
Missing / not reported	4313	188	2272	8%	149	2041	7%	1.09	0.87‐1.35
History of cardiovascular events
Yes	3593	273	2002	14%	197	1591	12%	1.24	1.03‐1.49	0.62
No	6729	404	3700	11%	319	3029	11%	1.17	1.01‐1.35
Missing / not reported	3611	188	1932	10%	149	1679	9%	1.09	0.87‐1.35
History of hypertension
Yes	2093	140	1219	11%	107	874	12%	1.15	0.90‐1.49	0.76
No	7527	537	4143	13%	409	3384	12%	1.21	1.06‐1.37
Missing / not reported	4313	188	2272	8%	149	2041	7%	1.09	0.88‐1.35
History of diabetes mellitus
Yes	709	62	372	17%	56	337	17%	1.12	0.78‐1.61	0.70
No	7316	555	3927	14%	427	3389	13%	1.21	1.06‐1.37
Missing / not reported	5908	248	3335	7%	182	2573	7%	1.11	0.91‐1.34
Geographical region
Northern America	3569	184	2004	9%	159	1565	10%	1.08	0.87‐1.34	0.17
Northern, Western & Southern Europe	7440	403	4030	10%	320	3410	9%	1.08	0.93‐1.26
Eastern Europe	1955	234	1030	23%	151	925	16%	1.44	1.17‐1.77
Australia & New Zealand	342	20	216	9%	11	126	9%	1.42	0.68‐2.97
Other	226	13	123	11%	13	103	13%	0.90	0.42‐1.93
Missing / not reported	401	11	231	5%	11	170	6%	0.98	0.42‐2.26
Tumour stage
Metastatic / advanced	8113	692	4482	15%	527	3631	15%	1.20	1.07‐1.34	0.76
Not metastatic / not advanced	4039	63	2116	3%	45	1923	2%	1.28	0.87‐1.87
Missing / not reported	1781	110	1036	11%	93	745	12%	0.92	0.69‐1.22
Planned Hb ceiling
Planned Hb ceiling (cat. 1)										0.98
≤Hb 13.0 g/dL	3043	209	1624	13%	157	1419	11%	1.19	0.97‐1.47
Hb 13.0 ‐ ≤15.0 g/dL	10193	599	5631	11%	468	4562	10%	1.16	1.03‐1.32
Hb >15.0 g/dL	494	29	259	11%	23	235	10%	1.22	0.70‐2.11
Other	203	28	120	23%	17	83	20%	1.12	0.61‐2.06
Planned Hb ceiling (cat. 2)										0.88
≤Hb 13.0 g/dL	3043	209	1624	13%	157	1419	11%	1.19	0.97‐1.47
Hb 13.0 – ≤14.0 g/dL	6816	381	3733	10%	322	3083	10%	1.12	0.97‐1.31
Hb 14.0 – ≤15.0 g/dL	3377	218	1898	11%	146	1479	10%	1.25	1.01‐1.54
>Hb 15.0 g/dL	494	29	259	11%	23	235	10%	1.22	0.70‐2.11
Other	203	28	120	23%	17	83	20%	1.12	0.61‐2.06
Study level characteristics
Treatment population
Treatment population (cat. 1)
Chemotherapy	10441	605	5676	11%	490	4765	10%	1.10	0.98‐1.24	0.42
Radiochemotherapy	737	31	368	8%	20	369	5%	1.50	0.85‐2.63
Radiotherapy	799	19	408	5%	12	391	3%	1.52	0.74‐3.14
Mixed	266	17	175	10%	7	91	8%	1.53	0.63‐3.69
None	1690	193	1007	19%	136	683	20%	1.33	1.06‐1.66
Treatment population (cat. 2)
Chemotherapy	10441	605	5676	11%	490	4765	10%	1.10	0.98‐1.24	0.27
Radiotherapy / radiochemotherapy	1536	50	776	6%	32	760	4%	1.51	0.97‐2.35
Mixed	266	17	175	10%	7	91	8%	1.53	0.63‐3.69
None	1690	193	1007	19%	136	683	20%	1.33	1.06‐1.66
Iron supplementation
Fixed iron supplementation	2589	71	1293	5%	60	1296	5%	1.17	0.83‐1.65	0.48
Iron supplementation as needed	11120	778	6232	12%	584	4888	12%	1.18	1.06‐1.32
Other	224	16	109	15%	21	115	18%	0.79	0.41‐1.51
Planned ESA treatment duration
Up to 8 weeks	415	21	256	8%	17	159	11%	0.96	0.50‐1.84	0.33
9‐16 weeks	4800	244	2738	9%	204	2062	10%	1.08	0.89‐1.30
> 17 weeks	3269	388	1701	23%	286	1568	18%	1.30	1.12‐1.52
Until end of chemo‐ or radiotherapy	5449	212	2939	7%	158	2510	6%	1.09	0.88‐1.34
Planned weekly ESA dosage
< 100 µg Darbepoetin or < 40000 IU Epoetin	4197	238	2297	10%	193	1900	10%	0.98	0.81‐1.19	0.12
= 100 µg Darbepoetin or = 40000 IU Epoetin	3081	240	1545	16%	190	1536	12%	1.36	1.12‐1.64
> 100 µg Darbepoetin or > 40000 IU Epoetin	3845	250	2076	12%	184	1769	10%	1.23	1.01‐1.49
Other	2810	137	1716	8%	98	1094	9%	1.11	0.85‐1.45
Planned frequency of ESA application
Three times per week or more frequent	6131	311	3458	9%	238	2673	9%	1.01	0.85‐1.20	0.03
Once per week	3948	303	1972	15%	231	1976	12%	1.40	1.18‐1.66
Every second week or less frequent	3036	180	1795	10%	122	1241	10%	1.25	0.99‐1.57
Other	818	71	409	17%	74	409	18%	0.93	0.67‐1.29
Placebo controlled trial
Yes	7657	594	4211	14%	456	3446	13%	1.21	1.07‐1.37	0.38
No	6276	271	3423	8%	209	2853	7%	1.09	0.91‐1.31
Randomisation
Adequate	3882	303	2047	15%	245	1835	13%	1.17	0.99‐1.39	0.98
Unclear	10051	562	5587	10%	420	4464	9%	1.17	1.03‐1.33
Concealment of allocation
Adequate	10595	744	5839	13%	559	4756	12%	1.20	1.08‐1.34	0.23
Unclear	3338	121	1795	7%	106	1543	7%	1.01	0.78‐1.31
Endpoint survival
Primary endpoint	3116	247	1547	16%	195	1569	12%	1.30	1.08‐1.57	0.41
Secondary endpoint	4313	213	2282	9%	161	2031	8%	1.10	0.89‐1.35
Safety /adverse events	6504	405	3805	11%	309	2699	11%	1.13	0.97‐1.32
Year of last patient randomized
1990‐1994	1447	95	890	11%	67	557	12%	0.95	0.69‐1.30	0.24
1995‐1999	1725	95	1001	9%	70	724	10%	0.96	0.70‐1.32
2000‐2004	7620	431	4105	10%	337	3515	10%	1.26	1.10‐1.46
2005‐2006	3141	244	1638	15%	191	1503	13%	1.18	0.98‐1.43
Source of data
Manufacturer	12229	846	6789	12%	641	5440	12%	1.19	1.07‐1.32	0.13
Clinical study group	1704	19	845	2%	24	859	3%	0.74	0.41‐1.35
*P value for likelihood‐ratio test, patients with missing data are excluded from the test, analysis based on one‐stage Cox fixed‐effects model stratified by study ESA=erythropoiesis‐stimulating agents