Dr Li on Frontline Treatment Considerations With IO-Based Combinations in Unresectable HCC

Daneng Li, MD, associate professor, Department of Medical Oncology & Therapeutics Research, co-director, Neuroendocrine Tumor Program, City of Hope, discusses considerations when choosing between treatment with immuno-oncology (IO)–based combination regimens or single-agent TKIs in the first-line setting for patients with advanced, unresectable hepatocellular carcinoma (HCC), highlighting which patient and disease factors influence these decisions.

The IO-based combinations of atezolizumab (Tecentriq) plus bevacizumab (Avastin) and durvalumab (Imfinzi) plus tremelimumab (Imjudo) are both approved by the FDA for the first-line treatment of patients with unresectable HCC; however, there has not yet been a head-to-head comparison between these two regimens, Li begins. Selecting between these 2 treatments depends on several factors, he states. In the phase 3 IMbrave150 trial (NCT03434379), the combination of atezolizumab and bevacizumab elicited an overall response rate (ORR) of 27.3% (95% CI, 22.5%-32.5%) in patients with unresectable HCC. Conversely, in the phase 3 HIMALAYA trial (NCT03298451), treatment with the combination of durvalumab and tremelimumab led to a 20.1% ORR in this population. In situations where patients present with bulky tumors or significant symptoms, a treatment associated with a higher ORR may be considered, he notes, adding that this strategy aims to reduce tumor size and potentially improve patients' well-being early in the treatment phase.

Furthermore, for patients with specific comorbidities, such as a history of variceal bleeding, extensive varices at high risk of bleeding, prior stroke or other thrombotic events, or poorly controlled hypertension, a treatment that does not target the VEGF pathway is advisable, he expands. In such cases, the use of dual immune checkpoint inhibitors, such as durvalumab plus tremelimumab, becomes a suitable option, Li says.

Patients with contraindications to immunotherapy may benefit from oral TKIs, making those a reasonable alternative to immunotherapy, he emphasizes. When treating patients with bulkier tumors and seeking a higher ORR, considering lenvatinib (Lenvima) instead of sorafenib (Nexavar) is prudent, given that lenvatinib is associated with a notably high ORR, Li continues.

Ultimately, the decision-making process between different frontline regimens revolves around individual patient considerations, including tumor size, symptoms, specific comorbidities, and contraindications to certain treatments, he says. Tailoring the treatment to suit the unique medical profile of each patient is pivotal for achieving the best possible outcome, Li concludes.