Liver Cancer最新文献

Introduction: KEYNOTE-240 showed a favorable benefit/risk profile for pembrolizumab versus placebo in patients with sorafenib-treated advanced hepatocellular carcinoma (HCC); however, prespecified statistical significance criteria for overall survival (OS) and progression-free survival (PFS) superiority were not met at the final analysis. Outcomes based on an additional 18 months of follow-up are reported.

Methods: Adults with sorafenib-treated advanced HCC were randomized 2:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo. Dual primary endpoints were OS and PFS assessed per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included objective response rate (ORR), assessed per RECIST v1.1 by BICR, and safety.

Results: 413 patients were randomized (pembrolizumab, n = 278; placebo, n = 135). As of July 13, 2020, median (range) time from randomization to data cutoff was 39.6 (31.7-48.8) months for pembrolizumab and 39.8 (31.7-47.8) months for placebo. Estimated OS rates (95% CI) were 17.7% (13.4-22.5%) for pembrolizumab and 11.7% (6.8-17.9%) for placebo at 36 months. The estimated PFS rate (95% CI) for pembrolizumab was 8.9% (5.3-13.6%) and 0% for placebo at 36 months. ORR (95% CI) was 18.3% (14.0-23.4%) for pembrolizumab and 4.4% (1.6-9.4%) for placebo. Immune-mediated hepatitis events did not increase with follow-up. No viral hepatitis flare events were reported.

Conclusion: With extended follow-up, pembrolizumab continued to maintain improvement in OS and PFS and was associated with a consistent adverse event profile compared with placebo in patients with sorafenib-treated advanced HCC. Although KEYNOTE-240 did not meet prespecified statistical significance criteria at the final analysis, these results together with the antitumor activity of second-line pembrolizumab observed in KEYNOTE-224 and the statistically significant and clinically meaningful OS and PFS benefits of second-line pembrolizumab in patients from Asia observed in KEYNOTE-394 reinforce the clinical activity of pembrolizumab in previously treated patients with advanced HCC.

Introduction: We aimed to investigate whether concurrent use of intrahepatic external beam radiotherapy (EBRT) is a viable option for patients with advanced hepatocellular carcinoma (HCC) undergoing tyrosine kinase inhibitor (TKI) therapy.

Methods: A total of 453 patients with Barcelona Clinic Liver Cancer stage C (BCLC C) HCC, who started first-line treatment with TKI with intrahepatic EBRT (TKI + RT, n = 97) or TKI without intrahepatic EBRT (TKI, n = 356) were analyzed. The overall survival (OS) and progression-free survival (PFS) were compared in the overall cohort, patients who received at least 8 weeks of TKI treatment and a propensity score-matched cohort.

Results: OS and PFS were better in those treated with TKI + RT than TKI (8.6 vs. 4.4 months and 4.5 vs. 2.3 months, respectively, with p < 0.001). Of note, the TKI + RT group demonstrated significantly longer time to intrahepatic tumor progression. In subgroup analysis, TKI + RT led to better OS than TKI in all subgroups and PFS was significantly improved in patients without extrahepatic metastasis and those with portal vein invasion. There was no significant difference in treatment discontinuation due to adverse events between the TKI + RT and TKI groups (32.0% vs. 37.9%, p = 0.34). Furthermore, patients treated with TKI + RT showed better liver function preservation over time compared to TKI without intrahepatic EBRT. Comparable treatment outcomes were observed between patients who received at least 8 weeks of TKI treatment and the propensity score-matched cohort.

Conclusion: Concurrent intrahepatic EBRT targeting the liver and/or macrovascular invasion can be a viable option to improve outcomes of BCLC stage C patients receiving TKI therapy with an aim to control intrahepatic progression and preserving the liver function.

Introduction: The association between smoking cessation and intrahepatic and extrahepatic cholangiocarcinoma (iCCA and eCCA) risk is unclear. Furthermore, the association in individuals with preexisting risk factors is unknown. We aimed to investigate the association between smoking status (especially smoking cessation) and CCA risk according to individuals' glycemic status.

Methods: In this nationwide cohort study, 9,520,629 adults without cancer who underwent national health screening by the Korean National Health Insurance Service in 2009 were followed up through 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for CCA were estimated after adjusting for potential confounders.

Results: During the 78.3 person-years of follow-up, 16,236 individuals were newly diagnosed with CCA. Quitters had a significantly lower risk of iCCA and eCCA compared to current smokers in all glycemic status groups (all p < 0.01). The HRs (95% CIs) for iCCA in current smokers and quitters were 1.33 (1.24-1.43) versus 0.98 (0.90-1.06) in individuals with normoglycemia, 1.49 (1.37-1.63) versus 1.17 (1.06-1.28) in individuals with prediabetes, and 2.15 (1.96-2.37) versus 1.58 (1.42-1.75) in individuals with diabetes, compared to never-smokers with normoglycemia. Current smokers with diabetes or prediabetes had a synergistically increased risk of iCCA (all p < 0.01). However, quitters with diabetes and prediabetes had an iCCA risk comparable to that of never-smokers. Analysis of eCCA yielded similar results. Smoking was not independently associated with the risk of the ampulla of Vater cancer. However, smoking combined with diabetes or prediabetes was associated with an increased risk of the ampulla of Vater cancer (all p < 0.05).

Conclusion: Smoking cessation was associated with a reduced risk of CCA, despite the synergistically increased risk in current smokers with diabetes and prediabetes. Our findings suggest a crucial opportunity to reduce the risk of CCA. More individualized and intensive cancer prevention education is needed against CCA.

Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or superselective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria.

Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, superselective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone.

Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and 3 patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status.

Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug-free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.

Introduction: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC).

Methods: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups.

Results: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group.

Conclusions: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver.

Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC.

Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab.

Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9-18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8-20]; two or more prior lines, 13% [95% CI, 7-20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment.

Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.