Revolutionizing Liver Cancer Treatment
The fight against hepatocellular carcinoma (HCC), a prevalent form of liver cancer, has taken a significant leap forward. A recent clinical trial has shown that a combination of lenvatinib and anti-PD-1 antibodies can convert unresectable HCC into a resectable form.
The Source Article Details
Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial. by Wenwen Zhang et al. in 2023.
The Source Article's Abstract
Over 70% of the patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage and lose the opportunity for radical surgery. Combination therapy of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first-line and second-line treatment of advanced HCC. However, few studies have prospectively evaluated whether TKIs plus anti-PD-1 antibodies could convert unresectable intermediate-advanced HCC into resectable disease.
This single-arm, phase II study enrolled systemic therapy-naive adult patients with unresectable Barcelona Clinic Liver Cancer stage B or C HCC. Patients received oral lenvatinib one time per day plus intravenous anti-PD-1 agents every 3 weeks (one cycle). Tumor response and resectability were evaluated before the fourth cycle, then every two cycles. The primary endpoint was conversion success rate by investigator assessment.
Of the 56 eligible patients enrolled, 53 (94.6%) had macrovascular invasion, and 16 (28.6%) had extrahepatic metastasis. The median follow-up was 23.5 months. The primary endpoint showed a conversion success rate of 55.4% (31/56). ORR was 53.6% per mRECIST and 44.6% per RECIST 1.1. Median PFS was 8.9 months, and median OS was 23.9 months.
Lenvatinib plus anti-PD-1 antibodies demonstrate promising efficacy and tolerable safety as conversion therapy in unresectable HCC. Pre-existing CD8(+) cells are identified as a promising biomarker for response to this regimen.
The Source Article References
- The past, present and future of conversion therapy for liver cancer by Song, 2021 in Am J Cancer Res
- A phase IB study of Lenvatinib (Len) plus Nivolumab (Niv) in patients (Pts) with Unresectable hepatocellular carcinoma (Uhcc): study 117 by Kudo, 2020 in JCO
- 987P A phase IB study of the PD-1 antagonist Cs1003 plus Lenvatinib (LEN) in Chinese patients (Pts) with the first-line (1L) Unresectable hepatocellular carcinoma (uHCC).Annals of oncology by Shen, 2020 in Annals of Oncology
- Phase 2 study of Ak104 (Pd-1/Ctla-4 Bispecific antibody) plus Lenvatinib as first-line treatment of Unresectable hepatocellular carcinoma by Bai, 2021 in JCO
- Sintilimab plus Lenvatinib as conversion therapy in patients with Unresectable locally Intermediate to advanced hepatocellular carcinoma: a single-arm, single-center, open-label, phase 2 study by Wang, 2022 in JCO
- A phase II trial of Lenvatinib plus Toripalimab and hepatic arterial infusion chemotherapy as a first-line treatment for advanced hepatocellular carcinoma by He, 2021 in JCO
- The safety and efficacy of Transarterial Chemoembolization (Tace) + Lenvatinib + programmed cell death protein 1 (Pd-1) antibody of advanced Unresectable hepatocellular carcinoma by Zhang, 2022 in JCO
- A phase 1B trial of Lenvatinib (Len) plus Pembrolizumab (Pem) in patients (Pts) with Unresectable hepatocellular carcinoma (Uhcc) by Ikeda, 2018 in JCO
- A phase IB trial of Lenvatinib (LEN) plus Pembrolizumab (PEMBRO) in Unresectable hepatocellular carcinoma (uHCC): updated results by Llovet, 2019 in Annals of Oncology
- Regulation of Antitumour Cd8 T-cell immunity and Checkpoint blockade Immunotherapy by Neuropilin-1 by Leclerc, 2019 in Nat Commun
- Chinese expert consensus on conversion therapy of immune Checkpoint inhibitors combined Antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2021 edition) by Cao, 2021 in Eletronic Journal of Liver Tumor
Citing the Source Article (APA)
Zhang, W., Tong, S., Hu, B., Wan, T., Tang, H., Zhao, F., Jiao, T., Li, J., Zhang, Z., Cai, J., Ye, H., Wang, Z., Chen, S., Wang, Y., Li, X., Wang, F., Cao, J., Tian, L., Zhao, X., Chen, M., Wang, H., Cai, S., Hu, M., Bai, Y., Lu, S. (2023). Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial.. Journal for immunotherapy of cancer, 11(9). 10.1136/jitc-2023-007366
The Game-Changing Combination
Lenvatinib, a tyrosine kinase inhibitor, and anti-PD-1 antibodies, which are immune checkpoint inhibitors, have been combined to create a groundbreaking treatment. The study enrolled patients with unresectable HCC and treated them with this combination.
Impressive Clinical Outcomes
The results are nothing short of remarkable. With a conversion success rate of 55.4%, the study has shown that this treatment can make surgery a viable option for patients who previously had no hope of it.
Furthermore, the study identified pre-existing CD8(+) cells as a potential biomarker for treatment response, adding another layer to personalized medicine.
FAQs and Implications
- Who can benefit from this treatment? Patients with unresectable HCC.
- What are the side effects? Grade ≥3 treatment-related adverse events were observed in 42.9% of patients.
- What’s next? Further studies to validate these findings and explore long-term outcomes.
With these promising results, the medical community is abuzz with the possibilities this opens up for liver cancer treatment. What do you think? Share your thoughts below.