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Sunday Poster Session

Category: Liver

P0972 - Efficacy of Immune Checkpoint Inhibitors in Combination With TKIs in Hepatocellular Carcinoma: A Systematic Review of Clinical Trials

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Presenting Author(s)

MA

Mukarram Jamat Ali, MD (he/him/his)

Howard University Hospital
Washington, DC

Mukarram Jamat Ali, MD¹, Wajeeha Aiman, MBBS², Muhammad Ashar Ali, MD³
¹Howard University Hospital, Washington, DC; ²Saint Michael's Medical Center, Newark, NJ; ³St. Mary's and St. Clare's Hospital, New York Medical College, Denville, NJ

Introduction: Hepatocellular carcinoma (HCC) is increasing worldwide and is often diagnosed at an advanced stage
with no curative treatment. HCC frequently has an immunosuppressed microenvironment and therefore
immune checkpoint inhibitors (ICI) can be effective in these tumors. Tyrosine kinase inhibitors (TKIs)
bind with tyrosine receptors leading to antiangiogenic effects. In this systematic review, we will assess
the efficacy of ICIs in combination with TKIs in HCC.

Methods: Literature search was performed on PubMed and Embase with Mesh and Emtree terms, “Hepatocellular
Carcinoma”, AND “ICI” from the inception of data till 2/30/23. We screened 3,741 articles and included
2 randomized clinical trials (RCT, N=1,380) and 10 nonrandomized clinical trials (nRCTs, N=404). We
followed PRISMA guidelines in conducting this systematic review.

Results: In an RCT by Kelly et al. (N=837) on newly diagnosed (ND) HCC patients, OR/CR/PR was 11%/1%/11%
with cabozantinib + atezolizumab vs. 4%/0/4% with sorafenib. HRs of PFS and OS were 0.63 (0.44–0.91)
and 0.90 (0.69–1.18). Preliminary results of an RCT by Chan et al. (N=543) on ND HCC patients showed
HRs of PFS and OS as 0.52 (0.41-0.65) and 0.62 (0.49-0.80), respectively in favor of camrelizumab +
rivoceranib vs. sorafenib. In 7 early phase nRCTs (N=233) on newer combinations of ICI with tyrosine
kinase inhibitors showed OR/CR/PR in 36%/2%/34% of the ND HCC patients. In 3 clinical trials on ICI
combination with tyrosine kinase inhibitors (TKIs) (N=171) on patients with relapsed/refractory (RR)
HCC, ORR, CR, and PR were 21%, 1.1%, and 20%, respectively. Table.

Discussion: Cabozantinib + atezolizumab, and camrelizumab + rivoceranib showed significantly better clinical
responses and survival rates as compared to sorafenib in ND HCC patients. Newer combinations of ICIs
with TKIs have shown promising results in early-phase trials in both previously treated and untreated
patients with HCC. However, more large-scale multicenter RCTs are needed to confirm these results.

NCT #

Study

Medications

Median OS

HR of OS

ORR

Median PFS

HR of PFS

NCT03092895

Mei et al. 2021

Camrelizumab + Apatinib

13. 1 mo

10.70%

3 (10.7%

16(57.1

9(32.1%

3.8 mo

NCT03289533

Kudo et al. 2021

Avelumab + Axitinib

14.1 mo

13.60%

3(13.6%

12(54.5%

6(27.3%

5.5 mo

NCT03755791

Kelley et al. 2022

837

Cabozantinib + Atezolizumab 432

15.4 mo

HR 0·90 (96% CI 0·69–1·18); p=0·44

47 (11%)

1 (< 1%)

46 (11%)

290 (67%)

61 (14%)

6.8 mo

0·63 (99% CI 0·44–0·91); p=0·0012

Sorafenib 217

15.5 mo

8 (4%)

132 (61%)

44 (20%)

4.2 mo

Cabozantinib 188

12 (6%)

145 (77%)

20 (11%)

5.8 mo

0·71 (99% CI 0·51–1·01); p=0·011 vs S

NCT03764293

Chan et al. 2022

543

Camrelizumab +rivoceranib (N=272)

22.1 mo

0.62 [95% CI 0.49-0.80]

25.4%

5.6 mo

0.52 [95% CI 0.41-0.65]

Sorafenib (N=271)

15.2 mo

5.9%

3.7 mo

NCT03794440

Ren et al. 2021

595

Sintilimab+Bevacizumab (n=380)

not reached (NR)

HR 0·57, 95% CI 0·43–0·75; p< 0·0001

75 (21%)

189 (52%)

98 (27%)

4·6 mo

0·56, 95% CI 0·46–0·70; p< 0·0001

Sorafenib (n=191)

10·4 mo [8·5-NR]

7 (4%)

103 (60%)

57 (33%)

2·8 mo

NCT03841201

Vogel et al. 2022

Nivolumab + Lenvatinib

27.1 mo

28%

6%,

22.00%

46.00%

12.00%

9.0 mo

NCT04044313

Lai et al. 2022

Lenvatinib, Toripalimab + FOLFOX-HAIC

17.9 mo

23 (63.9%)

9 (25%)

2 (5.6%)

10.4 mo

NCT04052152

Chen et al. 2022

Sintilimab + Anlotinib

12.2 mo

NCT04172571

Han et al. 2022

Penpulimab + Anlotinib

Not R

8.8 mo

NCT04411706

Li et al. 2022

Sintilimab + Apatinib + Capecitabine

Not R

50.0%

23 50%

19 (41.3%)

4 (8.7%)

9.0 mo

NCT03941873

Zhang et al., 2022

Sitravatinib+ Tislelizumab N=22

52.7% (95% CI: 23.2-75.5)

2 (10%)

4.8 mo (95% CI: 3.2-6.9

NCT04072679

Zhang et al, 2020

Sintilimab + IBI305 N = 29

7 (24%)

15 (52%)

7 (24%)

NCT03463876

Xu et al., 2021

120

Camrelizumab + Apatinib

22.5% (27/120; 95% CI, 15.4-31.0)

OS=Overall survival, ORR= Overall response rate, CR=complete response, PR= partial response, SD= Stable disease, PD= Progressive disease, HR= Hazard ratio

Table: Trial for TKI plus ICIs in HCC

Disclosures:

Mukarram Jamat Ali indicated no relevant financial relationships.

Wajeeha Aiman indicated no relevant financial relationships.

Muhammad Ashar Ali indicated no relevant financial relationships.

Mukarram Jamat Ali, MD¹, Wajeeha Aiman, MBBS², Muhammad Ashar Ali, MD³. P0972 - Efficacy of Immune Checkpoint Inhibitors in Combination With TKIs in Hepatocellular Carcinoma: A Systematic Review of Clinical Trials, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.