Despite the high unmet needs within hepatocellular carcinoma (HCC), the market was stagnant from 2007 until 2018, when the FDA approved Eisai’s Lenvima (lenvatinib) in first-line advanced HCC. The current landscape has seen a rapid change. The needs in the HCC space are likely to be met in the near future, as many new therapies entering the market have different mechanisms of action (MOA) and are aiming to meet needs in different treatment settings. The high variety of pipeline products for the early, intermediate and advanced HCC settings brings hope for improvements to the cure rate for early stage HCC and survival for all stages of disease, according to GlobalData, a leading data and analytics company.
The result of Phase III IMbrave150 study demonstrated that the combination of systemic bevacizumab therapy Genentech’s Avastin and immunotherapy treatment Tecentriq (atezolizumab) for first-line advanced HCC, approved in May 2020, improved overall survival and progression-free survival than the previous standard of care, Bayer’s Nexavar (sorafenib).
Patients with advanced HCC are not suitable for curative treatments due to the extent of the disease and reduced liver function, therefore, non-curative treatments such as systemic therapy aim to escalate survival and improve the patient’s quality of life. Numerous ongoing Phase III clinical trials are aiming to expand HCC treatment options even further.
Mandana Emamzadeh continues: “Current mechanisms of action (MOAs) under investigation in Phase III trials to treat patients with advanced HCC include multikinase inhibitors, angiogenesis inhibitors and immuno-oncology agents (PD-1/PD-L1 and CLTA-4 inhibitors). The Phase I and II pipeline also contains novel MOAs such as immunomodulators, protein/peptide-based cancer vaccines a stemness inhibitor, adoptive cellular therapy, and chemotherapy. Key opinion leaders interviewed by GlobalData noted that adoptive cellular therapy is an emerging novel target that may change HCC treatment practice.”
The HCC systemic therapy landscape has evolved not only in the advanced stage but also in the earlier stages of HCC. Currently, patients with early stage HCC receive surgical resection, transplantation and ablation.
Emamzadeh adds: “While adjuvant therapy has improved outcomes over surgery alone in other cancer types, there are no such therapies to decrease the incidence of recurrence in HCC. Similarly, patients with intermediate HCC with more widespread liver-confined disease have limited treatment options consisting of locoregional therapies such as transarterial embolization (TACE).
“Systemic therapies are being investigated in combination with surgery as adjuvant therapy for early stage patients and as combinations with TACE for intermediate-stage patients. Label expansions into early and intermediate HCC would be an effective strategy for companies to gain market share in this space.”