Hispanic Individuals are Underrepresented in Phase III Clinical Trials for Advanced Liver Cancer in the United States

Figures & data

Table 1 SEER 5-Year Age-Adjusted Incidence Rates for the ten Most Common Types of Cancer from 2015–2019

Cancer Site	All Races/Eth	NHW	NHB	NH AI/AN	NH A/PI	Hispanic (Any Race)	Ratio Hispanic to NHW
All Cancer Sites	444.5	476.3	459	420.4	308.3	354.3	0.74
Colon and Rectum	37.7	38.1	44.3	49	30.7	34.4	0.90
Liver	9.5	7.5	11	18.8	12.5	15.1	2.01
Pancreas	13.3	13.5	16.1	12.8	10	12	0.89
Lung and Bronchus	52	58.4	56.1	48.3	35.4	27.4	0.47
Melanoma of the Skin	21.5	31.1	0.9	8.3	1.3	4.4	0.14
Breast	128.3	137.6	129.6	111.3	106.9	99.9	0.73
Cervix Uteri	7.8	7.1	9	10.1	6.3	10	1.41
Prostate	112.7	110	183.4	70.3	59.6	88.6	0.81
Urinary Bladder	18.7	22.4	11.2	12.5	8.6	10.2	0.46
Kidney and Renal Pelvis	17.3	17.7	18.8	26.6	8.7	18.5	1.05

Notes: Rates are per 100,000 and are age-adjusted to the 2000 US Std Population (19 age groups - Census P25-1130).

Figure 1 Ten most frequent cancer sites in the US population per race/ethnicity. Cancer sites displayed from top to bottom: prostate, breast, lung and bronchus, colon and rectum, melanoma, urinary bladder, kidney and renal pelvis, pancreas, liver, endometrial. NHW=non-Hispanic white individuals, NHB=non-Hispanic black individuals. Rates are per 100,000 and age-adjusted to the 2000 US Std Population (19 age groups–- Census P25-1130) standard. Data acquired from SEER database for 2015–2019.

Figure 2 Incidence Rate-Ratio relative to non-Hispanic White individuals by race/ethnicity. Ratio of cancer incidence in (A) Hispanic individuals, (B) non-Hispanic black individuals (NHB), (C) non-Hispanic Asian/pacific islander individuals (NH A/PI), and (D) non-Hispanic American Indian/Alaska Native (NH AI/AN) individuals compared to non-Hispanic white individuals. Rates are per 100,000 and age-adjusted to the 2000 US Std Population (19 age groups–- Census P25-1130) standard sourced from SEER database.

Figure 3 Incidence and mortality rate of liver cancer by race/ ethnicity. (A) Incidence and (B) mortality rates per 100,000 cases from CDC USCS database for non-Hispanic white (NHW) individuals, non-Hispanic black (NHB) individuals, and Hispanic individuals.

Figure 4 Consort diagram. Specific search terms and filters yielded 389 studies using PubMed (National Library of Medicine), Embase (Elsevier), and Web of Science: Core Collection (Clarivate Analytics) for multinational phase III clinical oncology trials of patients with liver cancer. These were further filtered to exclude non-interventional trials or trials that were phase I II or IV (manual verification), yielding 17 studies. Thirteen of those studies sufficiently reported data on race and ethnicity.

Table 2 Multinational Phase III Clinical Trials of Liver Cancer in the Last 10 Years by Race/Ethnicity of Trial Participants

Trial Name, Identifier	Treatment	Total Patients	Ethnicity	Race							From Americas
			Hispanic	NHW	NHB	Asian	NH/OPI	AI/AN	MT1R	Other/NR
BRISK-FL NCT00858871	Brivanib, Sorafenib	1155								1155	152
BRISK-PS NCT00825955	Brivanib	395		188	16	184				7	67
NCT00699374	Sunitinib, Sorafenib	1074		223	16	829				6	NR
SEARCH NCT0901901	Sorafenib, Erlotinib	720								720	173
REACH NCT01140347	Ramucirumab	565	43	276	8	266				15	65
NCT01009593	Linifanib, Sorafenib	1035				689				346	NR
RESORCE NCT01774344	Regorafenib	573		206	8	234				125	NR
NCT01761266	Lenvatinib, Sorafenib	954	17	276	13	660	1	1		3	NR
CELESTIAL NCT01908426	Cabozantinib	707	30	394	19	241	3		1	49	167
REACH-2 NCT02435433	Ramucirumab	377	22	104	6	233			5	51	34
ClarIDHy NCT02989857	Ivosidenib	187	9	106	2	23	1	1		54	NR
IMbrave150 NCT03434379	Atezolizumab, Bevacizumab, Sorafenib	501	13	175	10	284		1		31	NR
KEYNOTE-240 NCT02702401	Pembrolizumab	413	35	213	19	165	1	6	8	1	37
TOPAZ-1 NCT03875235	Durvalumab, Gemcitabine, Cisplatin	685				386				299	374
CheckMate459 NCT02576509	Nivolumab, Sorafenib	743	15	395	5	332		1		10	295
HIMALAYA NCT03298451	Durvalumab, Tremelimumab, Sorafenib	1171		521	19	596	1			34	NR
COSMIC-312 NCT03755791	Cabozantinib, Atezolizumab, Sorafenib	1209		614	17	366	1	28		189	82
Total		12,464	184	3691	158	5488	8	38	14	3095	1446
% of total			1.48%	29.61%	1.27%	44.03%	0.06%	0.30%	0.11%	24.83%	11.60%
Total*		10,589	184	3691	158	5488	8	38	14	1220	1121
% of total*			1.74%	34.86%	1.49%	51.83%	0.08%	0.36%	0.13%	11.52%	10.59%
Total**		8869	184	3691	158	4413	8	38	14	575	747
% of total**			2.07%	41.62%	1.78%	49.76%	0.09%	0.43%	0.16%	6.48%	8.42%

Notes: *Excludes trials that did not report race or ethnicity. **Excludes trials that did not report race or ethnicity or only reported Asian individuals.

Abbreviations: NHW, non-Hispanic white individuals; NHB, non-Hispanic black individuals; NH/OPI, non-Hispanic/other pacific islander individuals; AI/AN, American Indian/Alaska native individuals; MT1R, more than one race; NR, data specifically on Americas not reported.

Figure 5 Multinational Studies of Liver Cancer from 2012–2022 per Race/ Ethnicity. Relative size of pie chart shows relative number of participants. Inner circles display information on ethnicity, outer circles display information on race.

Figure 6 Underrepresentation of Hispanic individuals in clinical trials for liver cancer. (A) difference in incident rate ratio (D-IRE) by race and ethnicity and (B) the ratio of incidence by race and ethnicity (R-IRE) for non-Hispanic white (NHW) individuals, non-Hispanic Asian/pacific islander (NH A/PI) individuals, non-Hispanic black (NHB) individuals, and Hispanic individuals. (C) number of liver cancer cases by race/ethnicity over time and proportion of participants enrolled in clinical trials for liver cancer over time.