Outcomes of Antineoplastic Immunotherapy at a Large Healthcare Organization: Impact of Provider, Race and Socioeconomic Status

Figures & data

Table 1 Patient Characteristics by Race (A) and Care Provider (B)

A
Factors	Whole Cohort (n = 1070) Frequency (%) or Mean (STD)	White (n = 783) Frequency (%) or Mean (STD)	Black (n = 122) Frequency (%) or Mean (STD)	p-value
Age (years), mean (STD)	64.34 (13.11)	64.3 (13.2)	63.8 (13.0)	0.647
Sex; n (%)
Female	459 (42.90)	320 (40.87)	66 (54.10)	0.006
Male	611 (57.10)	463 (59.13)	56 (45.90)
Insurance; n (%)
Medicaid	105 (9.95)	54 (6.99)	30 (24.59)	< 0.0001
Medicare	527 (49.95)	393 (50.91)	61 (50.00)
Private	423 (40.09)	325 (42.10)	31 (25.41)
Employment; n (%)
Employed	331 (36.90)	255 (39.11)	30 (29.13)	0.001
Retired	428 (47.71)	314 (48.16)	46 (44.66)
Unemployed	138 (15.38)	83 (12.73)	27 (26.21)
Care provider; n (%)
DOP	723 (67.76)	498 (63.76)	102 (83.61)	< 0.0001
COP	344 (32.24)	283 (36.24)	20 (16.39)
A
Factors	Whole Cohort (n = 1070) Frequency (%) or Mean (STD)	White (n = 783) Frequency (%) or Mean (STD)	Black (n = 122) Frequency (%) or Mean (STD)	p-value
Marital status; n (%)
Divorced	108 (10.15)	78 (10.01)	15 (12.40)	< 0.0001
Married	670 (62.97)	523 (67.14)	43 (35.54)
Single	186 (17.48)	109 (13.99)	50 (41.32)
Widowed	100 (9.40)	69 (8.86)	13 (10.74)
Performance Status; n (%)
0, 1, 2	919 (89.75)	679 (91.26)	104 (88.14)	0.27
3, 4	105 (10.25)	65 (8.74)	14 (11.86)
Immunotherapy (ICI); n (%)
NIVOLUMAB (PD1)	529 (49.44)	378 (48.28)	72 (59.02)	0.006
PEMBROLIZUMAB (PD1)	302 (28.22)	212 (27.08)	33 (27.05)
IPILIMUMAB (CTLA4)	190 (17.76)	160 (20.43)	8 (6.56)
ATEZOLIZUMAB (PD-L1)	32 (2.99)	20 (2.55)	6 (4.92)
DURVALUMAB (PD-L1)	15 (1.40)	11 (1.40)	3 (2.46)
AVELUMAB (PD-L1)	2 (0.19)	2 (0.26)	0 (0.00)
Comorbidity index; mean (STD)	9.76 (2.04)	9.74 (2.10)	9.98 (2.06)	0.25
Poverty level; n (%)
≤ 5%	447 (44.74)	367 (50.55)	8 (6.67)	< 0.0001
6–10%	325 (32.53)	235 (32.37)	42 (35.0)
≥11%	227 (22.72)	124 (17.08)	70 (58.33)
Stage; n (%)
I	5 (0.48)	1 (0.84)	4 (0.52)	0.6122
II	21 (2.01)	2 (1.68)	18 (2.33)
III	153 (14.63)	14 (11.76)	116 (15.05)
IV	867 (82.89)	102 (85.71)	633 (82.10)
Diagnosis; n (%)
NSCLC	383 (35.83)	258 (32.95)	70 (57.85)	<0.0001
Melanoma	256 (23.95)	224 (28.61)	5 (4.13)
RCC	49 (4.58)	38 (4.85)	4 (3.31)
Other	381 (35.64)	263 (33.59)	42 (34.71)
B
Factors	Whole Cohort (n = 1070) Frequency (%) or Mean (STD)	Disease-Oriented Provider (n =723) Frequency (%) or Mean (STD)	Community Oncology Provider (n =344) Frequency (%) or Mean (STD)	p-value
Age (years); mean (STD)	64.34 (13.11)	62.95 (13.95)	67.28 (10.59)	<0.0001
Sex; n (%)
Female	459 (42.90)	317 (43.85)	140 (40.70)	0.3315
Male	611 (57.10)	406 (56.15)	204 (59.30)
Race; n (%)
Black	122 (13.48)	102 (17.00)	20 (6.60)	<0.0001
White	783 (86.52)	498 (83.00)	283 (93.40)
Insurance; n (%)
Medicaid	105 (9.95)	74 (10.39)	31 (9.06)	0.0388
Medicare	527 (49.95)	336 (47.19)	190 (55.56)
Private	423 (40.09)	302 (42.42)	121 (35.38)
Employment; n (%)
Employed	331 (36.90)	249 (39.40)	82 (31.06)	0.0472
Retired	428 (47.71)	286 (45.25)	141 (53.41)
Unemployed	138 (15.38)	97 (15.35)	41 (15.53)
Marital status; n (%)
Divorced	108 (10.15)	71 (9.83)	37 (10.91)	0.1005
Married	670 (62.97)	452 (62.60)	216 (63.72)
Single	186 (17.48)	138 (19.11)	47 (13.86)
Widowed	100 (9.40)	61 (8.45)	39 (11.50)
Performance Status; n (%)
0, 1, 2	919 (89.75)	640 (90.14)	279 (88.85)	0.5312
3, 4	105 (10.25)	70 (9.86)	35 (11.15)
Immunotherapy (ICI); n (%)
NIVOLUMAB (PD1)	529 (49.44)	322 (44.54)	207 (60.17)	<0.0001
PEMBROLIZUMAB (PD1)	302 (28.22)	199 (27.52)	103 (29.94)
IPILIMUMAB (CTLA4)	190 (17.76)	172 (23.79)	15 (4.36)
ATEZOLIZUMAB (PD-L1)	32 (2.99)	17 (2.35)	15 (4.35)
DURVALUMAB (PD-L1)	15 (1.40)	11 (1.52)	4 (1.16)
AVELUMAB (PD-L1)	2 (0.19)	2 (0.28)	0 (0.00)
B
Factors	Whole Cohort (n = 1070) Frequency (%) or Mean (STD)	Disease-Oriented Provider (n =723) Frequency (%) or Mean (STD)	Community Oncology Provider (n =344) Frequency (%) or Mean (STD)	p-value
Comorbidity index; mean (STD)	9.76 (2.04)	9.49 (1.97)	10.32 (2.08)	<0.0001
Poverty level; n (%)
≤ 5%	447 (44.74)	283 (42.94)	163 (48.37)	0.0067
6–10%	325 (32.53)	206 (31.26)	117 (34.72)
≥11%	227 (22.72)	170 (25.80)	57 (16.91)
Stage; n (%)
I	5 (0.48)	5 (0.71)	0 (0.00)	0.4142
II	21 (2.01)	16 (2.28)	5 (1.46)
III	153 (14.63)	101 (14.41)	52 (15.20)
IV	867 (82.89)	579 (82.60)	285 (83.33)
Diagnosis; n (%)
NSCLC	383 (35.83)	196 (27.15)	187 (54.36)	<0.0001
Melanoma	256 (23.95)	227 (31.44)	26 (7.56)
RCC	49 (4.58)	32 (4.43)	17 (4.94)
Other	381 (35.64)	267 (6.98)	114 (3.14)

Abbreviations: STD, standard deviation; DOP, Disease Oriented Provider; COP, Community Oncology Provider; ICI, Checkpoint inhibitor; PD1, Programmed Death- 1 inhibitor; CTLA4, Cytotoxic T-Lymphocyte-Associated Antigen 4; PD-L1, Programmed Death Ligand-1 inhibitor; NSCLC, Non-Small Cell Lung Cancer; RCC, Renal Cell Carcinoma.

Table 2 Cox Regression on Overall Survival

Factor	Univariate Analysis		Multivariable Regression
	HR (95% CI)	p-value	HR (95% CI)	p-value
Age (per year increase)	1.008 (1.002, 1.014)	0.0077	1.01 (0.998, 1.02)	0.1309
Sex (Female vs Male)	1.02 (0.88, 1.19)	0.79
Race (Black vs White)	1.17 (0.92, 1.49)	0.21
Insurance
Medicaid vs Private	1.16 (0.90, 1.51)	0.26
Medicare vs Private	0.89 (0.75, 1.04)	0.15
Employment
Employed vs Unemployed	0.74 (0.58, 0.96)	0.02	0.78 (0.60, 1.03)	0.0775
Retired vs Unemployed	0.93 (0.73, 1.19)	0.57	0.89 (0.66, 1.19)	0.4356
Care provider
DOP vs COP	0.65 (0.55, 0.76)	<0.0001	0.68 (0.56, 0.84)	0.0002
Marital status
Divorced vs Widowed	1.01 (0.71, 1.44)	0.97
Married vs Widowed	1.05 (0.79, 1.38)	0.76
Single vs Widowed	1.24 (0.90, 1.70)	0.19
Performance Status (0, 1, 2 vs 3, 4)	0.46 (0.36, 0.57)	<0.0001	0.46 (0.35, 0.59)	<0.0001
Poverty level
<5% vs ≥11%	1.1 (0.89, 1.35)	0.385
6–10% vs ≥11%	1.1 (0.89, 1.37)	0.38
Comorbidity index	1.03 (0.99, 1.07)	0.11	0.94 (0.88, 0.995)	0.0333
Stage
Stage I/II vs Stage IV	0.45 (0.24, 0.84)	0.013	0.48 (0.25, 0.94)	0.0329
Stage III vs Stage IV	0.56 (0.44, 0.72)	<0.0001	0.57 (0.43, 0.76)	0.0001
Diagnosis
NSCLC vs Other	0.94 (0.79, 1.12)	0.4665	0.84 (0.68, 1.03)	0.0893
Melanoma vs Other	0.44 (0.35, 0.55)	<0.0001	0.44 (0.33, 0.58)	<0.0001
RCC vs Other	0.76 (0.52, 1.10)	0.1391	0.70 (0.47, 1.05)	0.0838

Notes: Univariate analysis - Compared to patients who were treated by community oncology providers (COPs), patients who were treated by disease-oriented providers (DOPs) had a lower hazard of death. The hazard ratio of death was 0.65 (95% CI: 0.55–0.76, p < 0.0001). Significant differences were also apparent comparing patients who had a melanoma diagnosis compared to “other” (HR of death 0.44; 95% CI: 0.33–0.58; p < 0.001), stage I/II disease compared to stage IV (HR of death 0.45; 95% CI: 0.25–0.94; p = 0.013) and stage III disease compared to stage IV (HR of death 0.56; 95% CI: 0.43–0.76; p < 0.001), older age compared to younger age (HR of death 1.008; 95% CI: 1.002–1.014; p = 0.0077) and employed compared to unemployed (HR of death 0.74; 95% CI: 0.58–0.96; p = 0.02). There is no significant OS difference comparing Black vs White patients (p = 0.21). Multivariable regression - After controlling for the effects of age, performance status, employment status, histopathologic diagnosis and disease stage there was a significant difference in OS comparing the patients who were treated by DOPs to those who were treated by COPs (p = 0.0002). Age and employment status did not remain statistically significant. The interpretation is similar for other factors.

Figure 1 Kaplan–Meier estimation of overall survival by care provider type.

Notes: The median survival (95% CI) was 15.8 (13.7, 19.2) months for patients who were treated by a DOP. The median survival (95% CI) was 8.7 (6.4, 10.3) months for patients who were treated by a COP. There was a significant difference in OS between DOPs and COPs (p < 0.001).

Table 3 The Results from Cox Regression with Death as Competing Risk (Fine and Gray Method) on Time to Adverse Event (TTAE)

Factor	Univariate Analysis		Multivariable Regression
	HR (95% CI)	p-value	HR (95% CI)	p-value
Age (per year increase)	1.01 (0.99, 1.03)	0.44	1.002 (0.98, 1.03)	0.85
Sex (Female vs Male)	0.81 (0.53, 1.25)	0.34	0.95 (0.61, 1.47)	0.80
Race (Black vs White)	0.996 (0.52, 1.92)	0.99
Insurance
Medicaid vs Private	0.57 (0.22, 1.46)	0.24
Medicare vs Private	1.16 (0.75, 1.79)	0.51
Employment
Employed vs Unemployed	1.49 (0.68, 3.25)	0.32
Retired vs Unemployed	1.53 (0.71, 3.28)	0.28
Care provider
DOP vs COP	1.88 (1.12, 3.15)	0.017	1.53 (0.88, 2.65)	0.13
Marital status
Divorced vs Widowed	1.04 (0.40, 2.71)	0.94
Married vs Widowed	1.04 (0.50, 2.19)	0.91
Single vs Widowed	0.99 (0.42, 2.34)	0.98
Performance Status (0, 1, 2 vs 3, 4)	1.06 (0.51, 2.22)	0.88
Poverty level
<5% vs ≥11%	1.7 (0.93, 3.08)	0.083
6–10% vs ≥11%	1.25 (0.65, 2.39)	0.503
Comorbidity index	1.03 (0.99, 1.07)	0.11	1.11 (0.97, 1.28)	0.12
Stage
Stage I/II vs Stage IV	0.93 (0.23, 3.85)	0.92
Stage III vs Stage IV	1.12 (0.63, 1.98)	0.70
Diagnosis
NSCLC vs Other	0.78 (0.43, 1.41)	0.411	0.78 (0.44, 1.39)	0.40
Melanoma vs Other	2.43 (1.47, 4.01)	0.0005	2.37 (1.42, 3.97)	0.001
RCC vs Other	1.51 (0.59, 3.88)	0.392	1.57 (0.61, 4.04)	0.35

Notes: Univariate analysis - Compared to patients who were treated by community oncology providers (COPs) patients who were treated by disease oriented providers (DOPs) were more likely to have an immune-related adverse event (irAE). The hazard ratio of having an irAE was 1.88 (95% CI: 1.12–3.15; p = 0.017). Comparing patients with a melanoma diagnosis to those with another diagnosis, those with melanoma were more likely to have an irAE. The hazard ratio of having an irAE was 2.43 (95% CI: 1.47–4.01; p = 0.0005). The interpretation is similar for other factors. There is no significant difference in time to adverse event (TTAE) based on race (p = 0.99). Multivariable regression - After controlling for the effects of age, gender, comorbidity index and diagnosis there was no significant difference in TTAE comparing the patients who were treated by COPs and patients who were treated by DOPs (p = 0.13). However, a significant difference in TTAE remains when comparing the patients who had melanoma and patients with other cancer types (p = 0.001).

Figure 2 Graphical representation of suggested academic and community site integration measures to address provider disparities.

Note: Arrow directionality represents which providers will receive primary benefit from the suggested measure (ie, integrated tumor boards will primarily benefit community oncology providers).