Apatinib is effective for treatment of advanced hepatocellular carcinoma Apatinib is effective for treatment of advanced hepatocellular carcinoma

Background: The prognosis for advanced hepatocellular carcinoma (HCC) remains clinically unsatisfying. Apatinib has proven to be a very effective treatment for advanced HCC in our previous retrospective study. Our aim in this study was to evaluate the efficacy, safety, and toxicity of apatinib in patients with advanced HCC. Methods: This single-arm, open-label phase II clinical trial enrolled patients with advanced HCC. These patients received apatinib, 500 mg once daily, until disease progression, unacceptable toxicity, consent withdrawal, or death. One treatment cycle consisted of 4 weeks of apatinib treatment. The response evaluation criteria in solid tumors (RECIST) was used to assess tumor response every 1–2 cycles. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were the overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and toxicity. Results: Between December 2016 and June 2018, 23 patients were enrolled in the study, 22 of whom were available for response evaluation. The cutoff date was August 10, 2018. The overall ORR and DCR were 30.4% and 65.2%, respectively. The median OS and PFS were 13.8 (95% CI: 5.3–22.3) and 8.7 (95% CI: 5.9–11.1) months, respectively. The most common treatment-related adverse events were proteinuria (39.1%), hypertension (34.8%), and hand-foot-skin reaction (34.8%). Conclusions: Apatinib showed robust clinical activity in patients with advanced HCC. Moreover, apatinib was safe to use, well tolerated, and had acceptable toxicity. (NCT03046979).

Purpose: We retrospectively evaluated the efficacy and safety of apatinib as a first-line treatment for advanced hepatocellular carcinoma (HCC) and explored whether drug-related hypertension (HTN) could predict its efficacy. Patients and Methods: This retrospective analysis included patients with advanced HCC who received oral treatment with apatinib. We evaluated the effectiveness by overall survival (OS), progression-free survival (PFS), time to progression (TTP), and disease control rate (DCR), and assessed the safety of the drug based on the occurrence of adverse events. In order to explore whether apatinib-related HTN can be used as a predictor of therapeutic effect, patients were divided into an HTN group and a non-HTN group and adjusted for propensity score-matched (PSM) to reduce mixed deviation. Subgroup analyses of negative prognostic factors for advanced HCC were also performed, including alpha-fetoprotein (AFP), Child–Pugh Score, macrovascular invasion, and extrahepatic metastasis. Results: A total of 208 patients were analyzed, of which 40.9% (n =85) developed drug-related HTN. For all patients, the OS was 13.4 months (95% CI, 12.2– 14.6), the PFS was 5.7 months (95% CI, 5.1– 6.3), and the TTP was 6.9 months (95% CI, 6.0– 7.8). The OS of the HTN group and the non-HTN group was 17.4 months (m) and 12.5m (p=0.001), and the PFS was 7.4m and 4.7m (p=0.000), respectively. After PSM, the OS (p=0.001) and PFS (p=0.003) of the HTN group were still significantly better than the non-HTN group. Subgroup analysis suggested that overall survival was significantly longer in patients with HTN when serum AFP ≤ 400 μg/L or extrahepatic metastases. Moreover, OS in the HTN group increased significantly with or without macrovascular invasion. In addition, through the analysis of two groups of patients with PFS> 6m and PFS≤ 6m, we know that the patients with drug-related HTN may develop resistance later, so they have longer survival time. Conclusion: Apatinib demonstrates compelling anti-cancer activity and acceptable safety in advanced HCC. Apatinib-related HTN can potentially predict prolonged survival in patients with advanced HCC.

Pancreatic cancer remains a highly lethal malignancy due to late-stage diagnosis and limited therapeutic options. This study presents the development and validation of a noninvasive circulating cell-free DNA (cfDNA)–based model for early pancreatic cancer detection. In a case–control study comprising 232 patients with pancreatic cancer and 235 healthy controls, the model demonstrated high diagnostic accuracy (AUC = 0.9799 in training; 0.9622 in validation). A prospective cohort study involving 1,926 individuals with diabetes and obesity established risk factors for pancreatic cancer and further assessed its clinical applicability. The model detected 75% of pancreatic cancer cases, including all stage 0 patients, with a lead time of up to 298 days, significantly outperforming CA19-9. Additionally, it demonstrates potential for distinguishing high-risk from low-risk pancreatic cysts, thereby facilitating more precise risk stratification. This study highlights the potential of cfDNA-based screening as a scalable, noninvasive tool for early pancreatic cancer detection, warranting further large-scale clinical validation to enhance patient outcomes. Significance: This study develops a cfDNA-based model for early pancreatic cancer detection, demonstrating high accuracy and prospective clinical validation. By enabling presymptomatic identification and risk stratification, this noninvasive approach enhances early intervention and improves outcomes, supporting potential clinical applicability and representing a meaningful step toward improving pancreatic cancer screening and management. See related commentary by Tsui and Lo, p. 10

Purpose: Patients with hepatocellular carcinoma (HCC) who might benefit most from anti-angiogenesis therapy remain unknown. In recent years, neutrophil-to-lymphocyte ratio (NLR), an indicator of inflammatory response, has received particular attention in HCC. Herein, we explored the prognostic value of pre-treatment NLR in individuals with unresectable intermediate and advanced hepatocellular carcinoma treated with apatinib, a second-line angiogenesis inhibitor. The findings of this study would assist in precision medicine and provide clinical decision support. Patients and Methods: This is a retrospective study in which 171 HCC patients attending Tianjin Medical University Cancer Institute and Hospital and treated with apatinib between January 2016 and July 2018 were enrolled. The prognosis of the patients based on NLR signatures was then analyzed. Results: Patients with a low pre-treatment NLR (NLR < 2.49) presented a significantly longer overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P = 0.043). Furthermore, a low pre-treatment NLR level could be used to predict a longer OS in patients with non-macrovascular invasion (P < 0.001). Independent of serum alpha-fetoprotein (AFP) levels, a low NLR level in this cohort of patients is associated with a longer OS. Conclusion: Pre-treatment NLR predicts the prognosis of patients with unresectable intermediate and advanced HCC treated with apatinib.