Successful conversion therapy for unresectable hepatocellular carcinoma is getting closer: A systematic review and meta-analysis

Abstract

BackgroundConversion therapy provides selected patients with unresectable hepatocellular carcinoma the opportunity to undergo a curative hepatectomy and achieve long-term survival. Although various regimens have been used for conversion therapy, their conversion rate and safety remain uncertain. Therefore, we conducted some meta-analyses to evaluate the efficacy and safety of several conversion regimens in order to elucidate the optimal regimen.MethodWe performed systematic literature research on PubMed, Embase, and the Web of Science until July 30, 2022. Chemotherapy, transcatheter arterial chemoembolization (TACE), molecular therapy (targeted therapy, immunotherapy, or a combination of both), and combined locoregional-systemic therapy were the conversion regimens we targeted.ResultsTwenty-four studies were included. The pooled conversion rates for chemotherapy, TACE, molecular therapy, and combined locoregional-systemic therapy were 13% (95% confidence interval [CI], 7%–20%; I² = 82%), 12% (95% CI, 9%–15%; I² = 60%), 10% (95% CI, 3%–20%; I² = 90%), and 25% (95% CI, 13%–38%; I² = 89%), respectively. The pooled objective response rates (ORR) for chemotherapy, TACE, molecular therapy, and combined locoregional-systemic therapy were 19% (95% CI, 12%–28%; I² = 77%), 32% (95% CI, 15%–51%; I² = 88%), 30% (95% CI, 15%–46%; I² = 93%), and 60% (95% CI, 41%–77%; I² = 91%), respectively. The pooled grade ≥3 AEs for chemotherapy, TACE, molecular therapy, and combined locoregional-systemic therapy were 67% (95% CI, 55%–78%; I² = 79%), 34% (95% CI, 8%–66%; I²= 92%), 30% (95% CI, 18%–43%; I² = 84%), and 40% (95% CI, 23%–58%; I² = 89%), respectively. Subgroup analyses showed the conversion rate, ORR and grade ≥3 AE rate for tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI) and locoregional therapy (LRT) were 33% (95% CI, 17%-52%; I² = 89%), 73% (95% CI, 51%–91%; I² = 90%), 31% (95% CI, 10%-57%; I² = 89%), respectively.ConclusionCombined locoregional-systemic therapy, especially TKI combined with ICI and LRT, may be the most effective conversion therapy regimen, associated with a significant ORR, conversion potential, and an acceptable safety profile.

Conversion therapy for initially unresectable hepatocellular carcinoma: Current status and prospects

“…Locoregionalsystemic combination therapies have a lower incidence of adverse reactions, and particularly grade ≥ 3 adverse events (AEs). The incidence of adverse reactions was 67% with chemotherapy, 34% with TACE, 30% with systemic therapies, and 40% with locoregional-systemic combination therapies (56). Subgroup analyses have confirmed the benefits of locoregional-systemic triple combination therapies.…”

“…Surgical resection can optimize the prognosis for patients with uHCC who have undergone successful conversion therapy. The OS rates at 1, 2, and 5 years postoperatively were 90%, 58%, and 42%, respectively, for patients who underwent conversion therapy (56). Patients with advanced HCC that was initially unresectable had a good long-term survival after undergoing concurrent chemoradiotherapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) conversion therapy in the curative resection group compared to the non-surgery group (49.6% vs. 9.8% at 5 years; p < 0.001) (38).…”

“…Results indicated that locoregional plus systemic combination therapy had the highest conversion rate at 25%, followed by TACE at 13%, chemotherapy at 12%, and systemic therapy at 10% (56). Locoregional plus systemic combination therapy had the highest ORR at 60%, while chemotherapy had the lowest at 19% (56). The other therapies had an ORR ranging from 30% to 32% (56).…”

“…A meta-analysis of 24 studies was performed to determine the conversion rates and ORR of different therapies. Results indicated that locoregional plus systemic combination therapy had the highest conversion rate at 25%, followed by TACE at 13%, chemotherapy at 12%, and systemic therapy at 10% (56). Locoregional plus systemic combination therapy had the highest ORR at 60%, while chemotherapy had the lowest at 19% (56).…”

“…Locoregional plus systemic combination therapy had the highest ORR at 60%, while chemotherapy had the lowest at 19% (56). The other therapies had an ORR ranging from 30% to 32% (56). Locoregionalsystemic combination therapies have a lower incidence of adverse reactions, and particularly grade ≥ 3 adverse events (AEs).…”