Late combination of transarterial chemoembolization with apatinib and camrelizumab for unresectable hepatocellular carcinoma is superior to early combination

Abstract

Objective The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it. Methods In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS. Results A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8–30.5 months) and the median PFS was 15.7 months (95% CI: 14.7–16.6 months). The ORR was 58.8% (95% CI: 47.2–69.6) and DCR reached 81.2% (95% CI: 71.0–89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060–0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184–0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed. Conclusion TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination.

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

“…A total of 97 were excluded by duplicating, 1,353 by screening titles and abstracts, and another 22 more by reading the full text. Finally, 15 records were assessed to be eligible for this meta-analysis ( 21 , 25 , 30 – 42 ) ( Figure 1 ).…”

“…ORR was evaluated in all included trials ( 21 , 25 , 30 – 42 ), and the pooled ORR and 95% CI was 0.606 (0.528-0.682, Figure 3 ) using the random effect model. No publication bias was identified using the funnel plot ( Supplementary Figure 3 ) and Egger’s and Begg’s tests (0.4223 and 0.4879, respectively), and the result was not influenced by any one of the included studies ( Supplementary Figure 4 ).…”

“…The DCR was also evaluated in all included trials ( 21 , 25 , 30 – 42 ), and the corresponding rates ranged from 70.0% to 100%. Using the random effect model, the pooled DCR was 0.885 with the 95%CI of 0.835–0.927 ( Figure 4 ).…”

“…PFS at 0.5, 1, 1.5, and 2 years were evaluated in 13 ( 21 , 25 , 31 – 38 , 40 – 42 ), 13 ( 21 , 25 , 31 – 38 , 40 – 42 ), 11 ( 21 , 25 , 31 – 37 , 41 , 42 ), and 5 studies ( 21 , 32 , 34 , 37 , 42 ), and the pooled rates and 95%CI were 0.781 (0.688-0.862), 0.387 (0.293-0.486), 0.117 (0.076-0.165), and 0.069 (0.005-0.182), respectively ( Table 3 ). OS at 0.5, 1, 1.5, 2, and 3 years were evaluated in 12 ( 21 , 25 , 31 – 36 , 39 – 42 ), 12 ( 21 , 31 – 34 , 39 – 42 ), 12 ( 21 , 31 – 34 , 39 – 42 ), 9 ( 21 , 31 – 34 , 39 – 42 ), and 5 studies ( 21 , 31 – 33 , 42 ), and the pooled rates and 95%CI were 0.943 (0.902-0.975), 0.690 (0.585-0.786), 0.385 (0.246-0.533), 0.212 (0.117-0.324), and 0.056 (0.028-0.091), respectively ( Table 3 ).…”

“…TACE was adopted in 10 studies ( 21 , 30 – 33 , 38 – 42 ), and HAIC were in 5 studies ( 25 , 34 – 37 ), respectively. Table 4 exhibited the outcomes using TACE+TKIs+ICIs and HAIC+TKIs+ICIs, respectively.…”