Efficacy and Safety of TKI Plus PD-1 Inhibitors in Elderly uHCC Patients: A Retrospective Study

Abstract

To explore the efficacy and safety of sorafenib-or lenvatinib-based combination therapy with PD-1 inhibitors in elderly patients aged ≥75 years with unresectable hepatocellular carcinoma (uHCC). Patients and Methods: Systemic therapy-naïve uHCC patients who received first-line sorafenib-or lenvatinib-based combination therapy with PD-1 inhibitors were continually reviewed. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1. Adverse events (AEs) and immune-related AEs (irAEs) were also evaluated. Groups and subgroups were separated at the ages of 65 and 75 years and compared with 1:1 matching. Results: Total 169 eligible patients were enrolled, including 24 aged ≥75 years. Median progression-free survival (PFS) and overall survival (OS) in these 24 elderly patients were 4.6 (95% CI: 2.6-6.6) months, and 17.0 (95% CI: 11.2-22.8) months, with 3-, 6-, 12month OS rate at 82.90%, 73.70%, and 57.50%. Age ≥75 years was confirmed to be a risk factor influencing PFS among patients aged ≥65 years. Adverse events (AEs) were recorded in all these 24 elderly patients, with seven patients experiencing immune-mediated AEs (irAEs). Nearly 30% of elderly patients stopped treatment due to AEs (16% of these due to irAEs). No statistical differences were found in all efficacy endpoints at the cutoff age of 65 years. Conclusion: For patients aged ≥75 years, application of PD-1 inhibitors in combination with sorafenib or lenvatinib is promising, but this has to be done with caution and needs to be confirmed by future prospective studies.

The safety and efficacy of TACE combined with HAIC, PD-1 inhibitors, and tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a retrospective study

“…HAIC is a continuous infusion of chemotherapy through the tumor supply artery, which significantly increases the local drug concentration and exerts anti-tumor effects in the liver and hepatic tumors. Additionally, PD-1 inhibitors and tyrosine kinase inhibitors have been found in several clinical studies to have effective anti-tumor effects when used in the treatment of advanced HCC ( 18 , 19 ). In addition, in second-line treatment of some patients with refractory advanced HCC, regorafenib and cabozantinib were associated with longer OS compared to placebo, while in patients with AFP >400 ng/mL, regorafenib, cabozantinib and remolizumab were associated with longer PFS and OS compared to placebo ( 20 , 21 ).Therefore, TACE combined with HAIC, targeted therapy, and immunotherapy may serve as a new treatment modality for patients with unresectable HCC.…”

Estimation of the effect of atezolizumab plus bevacizumab on pulmonary arterial hypertension using computed tomography in HCC patients

“…Interestingly, advanced age and advanced HCC were shown to be factors related to the increment of mPA-D and mPA-D/aAo-D after Atez/Bev treatment. Elderly patients reportedly have a higher likelihood of not being able to complete the trials due to toxicity and a high rate of adverse events when taking TKIs plus PD-1 inhibitors 42 . Therefore, caution should be exercised during the administration of Atez/Bev to elderly patients to avoid the development of side effects.…”