BackgroundUnresectable hepatocellular carcinoma (u-HCC) still accounts for the majority of newly diagnosed HCC which with poor prognosis. In the era of systemic therapy, combination therapy with programmed cell death protein-1 (PD-1) inhibitors and tyrosine kinase inhibitors (TKIs) has become mainstream. Hepatic arterial infusion chemotherapy (HAIC) as a local treatment has also shown a strong anti-tumor effect. This study aimed to investigate the efficacy and safety of HAIC, PD-1 inhibitors plus TKIs for u-HCC.MethodsThis retrospective study included patients with initially u-HCC between October 2020 to April 2022 who had received at least one cycle of therapy with HAIC, PD-1 inhibitors plus TKIs. The primary outcome included overall response rate (ORR), the disease control rate (DCR), surgical conversion rate, progression-free survival (PFS) and treatment-related adverse events.ResultsA total of 145 patients were included in the study. The median treatment cycle of HAIC and PD-1 inhibitors were 3 and 4, respectively. According to the modified RECIST criteria, the best ORR was 57.2% (83/145), 9 had achieved complete response (CR), DCR was 89.7% (130/145). Median time to achieve CR or PR was 65 days. Surgical conversion rate was 18.6% (27/145), seven patients (7/27,25.9%) achieved pathological complete response (pCR). The median follow-up was 12.5 months (4.5-20 months), and the median PFS was 9.7 months. Subgroup analysis showed that Child-pugh A patients had higher DCR (92.2% vs 79.3%, p=0.041) than Child-pugh B patients, as well as increased successful conversion rate (22.4% vs 3.4%, p=0.019). Patients without vascular invasion and extrahepatic metastases showed higher PR (63.4% vs 43.3%, p<0.05) and ORR (73.2% vs 50.0%, p<0.05) than those with vascular invasion. The ORR (73.2% vs 45.5%, p<0.05) and DCR (95.1% vs 78.8%, p<0.05) were also significantly better than those of patients with extrahepatic metastases. HAIC regimen was not related to efficacy (All p>0.05). The incidence rate of grade 3/4 treatment-related AEs was 17.7% without fatal events.ConclusionThe triple combination therapy of HAIC and PD-1 inhibitors plus TKIs for patients with initially unresectable HCC exhibited satisfactory efficacy with tolerable toxicity.
With the development of immunotherapy, immune checkpoint inhibitors (ICIs) are widely used in clinical oncology and have achieved good results. ICIs could induce immune-related adverse events (irAEs) in cancer treatment, which warrant sufficient attention. Among them, immune myositis can manifest severe symptoms affecting the whole body, and immune myocarditis occurs with a low incidence but high fatality rate. Here we report a case of grade 3/4 adverse reactions in a patient with partial hepatectomy for malignancy after using ICIs and describe the clinical presentation, laboratory results, treatment, and prognosis. It emphasizes that clinicians should focus on being alert to irAEs in liver cancer patients who have received ICI therapy. The case we present is a 56-year-old male diagnosed with hepatocellular carcinoma. Right hepatic lobectomy was performed in April 2019. Postoperative follow-up showed that transcatheter arterial chemoembolization (TACE) combined with sorafenib (400 mg twice daily) failed to stop the recurrence of the tumor. In December 2020, the patient started to use Camrelizumab injections (200mg/injection every 21 days as a cycle). After 3 cycles, the patient had decreased muscle strength in both lower extremities with chest tightness, dyspnea, and expectoration (whitish sputum). The diagnosis was ICIs injection-induced immune myocarditis and myositis accompanied. The patient’s condition improved considerably by steroid pulse therapy timely. The case emphasizes that clinicians should focus on being alert to irAEs in liver cancer patients who have received ICI therapy.
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