Economic burden of dermatologic adverse drug reactions in the treatment of colorectal, non-small cell lung, and head and neck cancers with epidermal growth factor receptor inhibitors

Figures & data

Figure 1.  Sample selection.

Figure 2.  ADR observation period.

Figure 3.  Study period.

Table 1.  Patients with at least one dermatologic ADR and incidence rate of dermatologic ADR by cancer type.

EGFRI medications	Proportion of patients ≥ 1 adverse drug reaction	Incidence rate (95% CI) (per 100 patient-years)
Patients with CRC
All medication	819 (32.3%)	57.4 (53.5–61.3)
Cetuximab	704 (32.2%)	55.7 (51.6–59.8)
Panitumumab	115 (32.7%)	70.9 (58.0–83.9)
Patients with NSCLC
All medication	692 (20.5%)	44.2 (41.0–47.2)
Gefitinib	122 (15.4%)	32.0 (26.3–37.7)
Erlotinib	570 (22.0%)	48.2 (44.2–52.2)
Patients with HNC
Cetuximab	365 (36.4%)	56.1 (50.3–61.8)

Table 2.  Baseline characteristics—comparison between ADR and ADR-free patients.

Baseline characteristics	Patients with colorectal cancer			Patients with NSCLC			Patients with head and neck cancer
	ADR patients	ADR-free patients	p-value	ADR patients	ADR-free patients	p-value	ADR patients	ADR-free patients	p-value
Number of patients, n	746	1720	–	635	2688	–	333	638	–
Demographics
Age, mean ± SD	54.7 ± 7.5	55.2 ± 7.7	0.0307**	56.2 ± 7.3	57.6 ± 6.0	0.0005**	56.3 ± 6.7	56.2 ± 7.0	0.8137
Female, n (%)	337 (45.2)	805 (46.8)	0.4564	376 (59.2)	1367 (50.9)	0.0001**	66 (19.8)	120 (18.8)	0.7039
Index drug, n (%)
Cetuximab	642 (86.1)	1483 (86.2)	0.9148	0 (0.0)	0 (0.0)	–	333 (100.0)	638 (100.0)	–
Erlotinib	0 (0.0)	0 (0.0)	–	521 (82.0)	2018 (75.1)	0.0002**	0 (0.0)	0 (0.0)	–
Gefitinib	0 (0.0)	0 (0.0)	–	114 (18.0)	670 (24.9)	0.0002**	0 (0.0)	0 (0.0)	–
Panitumumab	104 (13.9)	237 (13.8)	0.9148	0 (0.0)	0 (0.0)	–	0 (0.0)	0 (0.0)	–
Charlson comorbidity index
Mean ± SD	7.34 ± 2.80	6.98 ± 2.87	0.0052**	6.89 ± 3.02	6.78 ± 3.06	0.4233	6.50 ± 3.11	5.94 ± 3.31	0.0106**
Comorbidities, n (%)
Chronic pulmonary disease	40 (5.4)	91 (5.3)	0.9422	166 (26.1)	679 (25.3)	0.6465	52 (15.6)	92 (14.4)	0.6188
Coagulopathy	42 (5.6)	106 (6.2)	0.6089	40 (6.3)	159 (5.9)	0.7138	13 (3.9)	29 (4.5)	0.6409
Depression	20 (2.7)	48 (2.8)	0.8785	19 (3.0)	69 (2.6)	0.5484	19 (5.7)	25 (3.9)	0.2037
Diabetes mild	97 (13.0)	167 (9.7)	0.0151**	70 (11.0)	196 (7.3)	0.0018**	41 (12.3)	69 (10.8)	0.4847
Deficiency Anemias	216 (29.0)	492 (28.6)	0.8600	173 (27.2)	794 (29.5)	0.2522	87 (26.1)	153 (24.0)	0.4620
Fluid electrolyte disorders	192 (25.7)	512 (29.8)	0.0418**	95 (15.0)	509 (18.9)	0.0195**	99 (29.7)	188 (29.5)	0.9321
Hypertension	179 (24.0)	373 (21.7)	0.2064	127 (20.0)	482 (17.9)	0.2256	90 (27.0)	198 (31.0)	0.1944
Hypothyroidism	24 (3.2)	53 (3.1)	0.8587	42 (6.6)	93 (3.5)	0.0003**	33 (9.9)	46 (7.2)	0.1441
Lymphoma	12 (1.6)	15 (0.9)	0.1064	9 (1.4)	48 (1.8)	0.5202	24 (7.2)	22 (3.4)	0.0089**
Metastatic cancer	590 (79.1)	1299 (75.5)	0.0547	438 (69.0)	1849 (68.8)	0.9263	205 (61.6)	359 (56.3)	0.1126
Other neurological disorders	30 (4.0)	65 (3.8)	0.7739	40 (6.3)	211 (7.8)	0.1836	18 (5.4)	36 (5.6)	0.8783
Pulmonary circulation disorders	19 (2.5)	76 (4.4)	0.0265**	53 (8.3)	195 (7.3)	0.3463	5 (1.5)	11 (1.7)	0.7959
Weight Loss	36 (4.8)	86 (5.0)	0.8546	25 (3.9)	104 (3.9)	0.9364	43 (12.9)	91 (14.3)	0.5625
Cancers, n (%)
Breast cancer	28 (3.8)	51 (3.0)	0.3072	41 (6.5)	122 (4.5)	0.0441**	8 (2.4)	14 (2.2)	0.8362
CRC	–	–	–	19 (3.0)	88 (3.3)	0.7176	19 (5.7)	25 (3.9)	0.2037
Cutaneous cell lymphoma	0 (0.0)	0 (0.0)	–	0 (0.0)	0 (0.0)	–	0 (0.0)	0 (0.0)	–
HNC	26 (3.5)	26 (1.5)	0.0017**	18 (2.8)	64 (2.4)	0.5075	–	–	–
Hepatocellular carcinoma	61 (8.2)	117 (6.8)	0.2256	15 (2.4)	60 (2.2)	0.8427	4 (1.2)	12 (1.9)	0.4297
Hodgkins lymphoma	2 (0.3)	4 (0.2)	0.8693	4 (0.6)	5 (0.2)	0.0529	0 (0.0)	0 (0.0)	–
Non hodgkins lymphoma	13 (1.7)	16 (0.9)	0.0856	12 (1.9)	53 (2.0)	0.8933	25 (7.5)	22 (3.4)	0.0051**
NSCLC	66 (8.8)	155 (9.0)	0.8955	–	–	–	45 (13.5)	101 (15.8)	0.3376
Pancreatic cancer	13 (1.7)	27 (1.6)	0.7549	7 (1.1)	47 (1.7)	0.2468	1 (0.3)	2 (0.3)	0.9720
Prostate cancer	9 (1.2)	22 (1.3)	0.8818	6 (0.9)	31 (1.2)	0.6526	8 (2.4)	9 (1.4)	0.2633
Skin cancer	21 (2.8)	21 (1.2)	0.0049**	20 (3.1)	64 (2.4)	0.2671	54 (16.2)	76 (11.9)	0.0615
Healthcare costs, mean ± SD
IP costs	21,852 ± 54,518	19,460 ± 48,992	0.1887	19,030 ± 46,960	20,738 ± 41,518	0.0013**	21,669 ± 43,813	15,924 ± 32,792	0.0559
ER costs	388 ± 1142	429 ± 2045	0.4764	382 ± 1320	495 ± 1684	0.0028**	654 ± 2367	574 ± 5273	0.1534
OP costs	83,370 ± 54,408	75,796 ± 58,141	<0.0001**	41,581 ± 44,793	41,819 ± 41,225	0.2993	69,601 ± 50,680	65,711 ± 51,454	0.1233
Pharmacy costs	3220 ± 5663	3000 ± 6182	0.5010	11,763 ± 8427	10,124 ± 7518	<0.0001**	2319 ± 4840	2226 ± 4848	0.7709
Healthcare resource utilization, mean ± SD
IP visits	0.8 ± 1.1	0.8 ± 1.2	0.6118	0.7 ± 1.1	0.9 ± 1.2	0.0002**	0.8 ± 1.1	0.7 ± 1.0	0.0891
Inpatient days	5.5 ± 10.3	6.6 ± 12.3	0.7450	5.6 ± 10.6	7.2 ± 12.1	0.0002**	5.5 ± 9.5	5.2 ± 12.2	0.1547
ER visits	0.5 ± 1.1	0.5 ± 1.4	0.7265	0.4 ± 1.3	0.5 ± 1.3	0.0030**	0.9 ± 3.3	0.6 ± 2.3	0.1311
OP visits	30.1 ± 13.6	28.0 ± 13.9	0.0006**	25.5 ± 13.6	25.7 ± 14.6	0.7677	34.4 ± 16.5	32.9 ± 17.9	0.1838

*Significant at the 5% level.

Table 3.  Comparison of healthcare resource utilization of ADR vs ADR-free patients by cancer type.

Medical services	Incidence rate (patient-years)		Incidence rate ratio DR patients vs ADR-free patients
	ADR patients	ADR-free patients	Unadjusted IRR (95% CI)	p-value	Adjusted IRR (95% CI)	p-value
Patients with CRC
IP admissions	1.76	1.68	1.05 (0.96–1.15)	0.2917	1.02 (0.93–1.12)	0.6227
IP days	14.02	13.51	1.04 (1.00–1.07)	0.0235**	1.01 (0.97–1.04)	0.7535
ER visits	0.89	0.73	1.21 (1.06–1.38)	0.0047**	1.18 (1.03–1.35)	0.0155**
OP	49.45	43.44	1.14 (1.12–1.16)	<0.0001**	1.12 (1.10–1.14)	<0.0001**
Other medical services	15.05	15.15	0.99 (0.96–1.02)	0.6688	0.97 (0.94–1.00)	0.0918
Patients with NSCLC
IP admissions	1.55	1.66	0.93 (0.85–1.02)	0.1224	0.96 (0.87–1.05)	0.3437
IP days	13.16	13.14	1.00 (0.97–1.03)	0.9181	1.02 (0.99–1.06)	0.1881
ER visits	1.01	0.79	1.29 (1.14–1.45)	<0.0001**	1.28 (1.13–1.45)	0.0001**
OP	41.95	31.36	1.34 (1.31–1.36)	<0.0001**	1.28 (1.25–1.30)	<0.0001**
Other medical services	12.66	11.31	1.12 (1.08–1.16)	<0.0001**	1.15 (1.11–1.19)	<0.0001**
Patients with HNC
IP admissions	1.23	0.82	1.50 (1.27–1.78)	<0.0001**	1.44 (1.22–1.71)	<0.0001**
IP days	11.14	7.26	1.53 (1.45–1.62)	<0.0001**	1.46 (1.38–1.54)	<0.0001**
ER visits	1.30	0.68	1.91 (1.60–2.28)	<0.0001**	1.85 (1.55–2.22)	<0.0001**
OP	42.04	33.55	1.25 (1.22–1.29)	<0.0001**	1.23 (1.20–1.27)	<0.0001**
Other medical services	10.27	9.26	1.11 (1.05–1.17)	0.0001**	1.07 (1.02–1.13)	0.0117**

**Significant at the 5% level.

Table 4.  Comparison of healthcare costs of ADR patients and ADR-free patients by cancer type.

Healthcare cost components US $2010	Monthly costs per patient Mean ± SD		Incremental monthly costs ADR vs ADR-free patients
	ADR patients [A]	ADR-free patients [B]	Unadjusted [A–B]	p-value	Adjusted [A–B]	p-value
Patients with CRC
EGFRI costs	3567 ± 5278	3047 ± 5463	520	<0.0001**	276	0.2435
Other pharmacy costs	473 ± 852	343 ± 874	131	<0.0001**	123	<0.0001**
Medical services costs	11,592 ± 12,068	9781 ± 15,472	1811	<0.0001**	1558	<0.0001**
IP	4565 ± 10,609	4027 ± 13,164	537	<0.0001**	517	0.3154
ER	72 ± 214	84 ± 710	−12	<0.0001**	−10	0.5509
OP	6287 ± 6525	5093 ± 7655	1195	<0.0001**	876	0.0040**
Other medical services	668 ± 1670	577 ± 1528	91	<0.0001**	37	0.5709
Total costs	15,631 ± 13,980	13,170 ± 17,216	2461	<0.0001**	2313	<0.0001**
Patients with NSCLC
EGFRI costs	1120 ± 1437	1070 ± 1847	50	<0.0001**	−42	0.5070
Other pharmacy costs	618 ± 946	418 ± 1044	200	<0.0001**	148	<0.0001**
Medical services costs	11,077 ± 17,856	7564 ± 12,994	3513	<0.0001**	3158	<0.0001**
IP	5196 ± 16,451	3714 ± 11,043	1482	<0.0001**	1111	0.0200**
ER	97 ± 324	103 ± 618	−6	<0.0001**	−10	0.6587
OP	5290 ± 6516	3247 ± 6513	2043	<0.0001**	1872	<0.0001**
Other medical services	494 ± 1402	499 ± 1533	−6	<0.0001**	−4	0.9261
Total costs	12,815 ± 17,929	9053 ± 13,306	3763	<0.0001**	3210	<0.0001**
Patients with HNC
EGFRI costs	2013 ± 4063	1902 ± 4161	111	<0.0001**	14	0.9102
Other pharmacy costs	356 ± 717	247 ± 533	109	<0.0001**	97	0.0200**
Medical services costs	10,170 ± 13,010	7535 ± 13,105	2634	<0.0001**	2178	0.0080**
IP	4834 ± 10,844	2900 ± 10,411	1934	<0.0001**	1702	0.0160**
ER	144 ± 509	82 ± 394	62	<0.0001**	46	0.0838
OP	4766 ± 6582	4077 ± 7157	689	<0.0001**	548	0.2475
Other medical services	426 ± 802	476 ± 1326	−50	<0.0001**	−83	0.1916
Total costs	12,539 ± 14,774	9684 ± 14,806	2855	<−0.0001**	2284	0.0120**

**Significant at the 5% level.