Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma.

PURPOSE: In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here. METHODS: Participants were randomly assigned to receive STRIDE, durvalumab, or sorafenib. PROs were assessed (preplanned secondary outcome) using the European Organization for Research and Treatment of Cancer 30-item Quality of Life Questionnaire and the 18-item HCC module. Time to deterioration (TTD), change from baseline and improvement rate in global health status/quality of life (GHS/QoL), functioning, and disease-related symptoms were analyzed. RESULTS: In total, 1,171 participants were randomly assigned to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389) and were evaluable for PRO assessments. Across treatment arms, compliance rates for PROs were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms. TTD in GHS/QoL, physical functioning, fatigue, appetite loss, and abdominal pain was numerically longer for both STRIDE and durvalumab versus sorafenib. Clinically meaningful deterioration in PROs was not observed in any treatment arm. However, TTD in nausea and abdominal swelling was numerically longer for STRIDE versus sorafenib, and the likelihood of clinically meaningful improvement in GHS/QoL, role, emotional and social functioning, and disease-related symptoms was greater with STRIDE and durvalumab versus sorafenib. PROs with STRIDE and durvalumab were generally similar. CONCLUSION: Compared with sorafenib, STRIDE and durvalumab were associated with clinically meaningful, patient-centered GHS/QoL, functioning, and symptom benefits in people with uHCC. These findings support the benefits of the STRIDE regimen compared with sorafenib for a diverse population reflective of the global uHCC population.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update.

PURPOSE: To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to update the 2020 guideline on systemic therapy for HCC. The panel updated the systematic review to include randomized controlled trials (RCTs) published through October 2023 and updated recommendations. RESULTS: Ten new RCTs met the inclusion criteria and were added to the evidence base. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) or durvalumab + tremelimumab (durva + treme) may be offered first-line for patients with advanced HCC, Child-Pugh class A liver disease, and Eastern Cooperative Oncology Group performance status 0-1. Where there are contraindications to these therapies, sorafenib, lenvatinib, or durvalumab may be offered first-line. Following first-line treatment with atezo + bev, second-line therapy with a tyrosine kinase inhibitor (TKI), ramucirumab (for patients with alpha-fetoprotein [AFP] ≥400 ng/mL), durva + treme, or nivolumab + ipilimumab (nivo + ipi) may be recommended for appropriate candidates. Following first-line therapy with durva + treme, second-line therapy with a TKI is recommended. Following first-line treatment with sorafenib or lenvatinib, second-line therapy options include cabozantinib, regorafenib for patients who previously tolerated sorafenib, ramucirumab (AFP ≥400 ng/mL), nivo + ipi, or durvalumab; atezo + bev or durva + treme may be considered for patients who did not have access to these therapies in the first-line setting, and do not have contraindications. Pembrolizumab or nivolumab are also options for appropriate patients following sorafenib or lenvatinib. Third-line therapy may be considered in Child-Pugh class A patients with good PS, using one of the agents listed previously that has a nonidentical mechanism of action with previously received therapy. A cautious approach to systemic therapy is recommended for patients with Child-Pugh class B advanced HCC. Further guidance on choosing between options is included within the guideline.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma.

Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.

Potential Impact of IMbrave150 Results in the Evolving Treatment Landscape of Advanced Hepatocellular Carcinoma: A Multidisciplinary Expert Opinion.

A virtual expert roundtable was convened on April 16, 2020, to discuss the evolving landscape of care for treating patients with advanced hepatocellular carcinoma (HCC) and discuss questions related to patient care and treatment selection. This commentary presents highlights from this discussion and provides an expert opinion about approaches to treatment for HCC in the Americas and the European Union. We anticipate that atezolizumab plus bevacizumab will become the standard of care for advanced HCC patients. However, this approach will make decisions regarding the sequencing of treatments for second-line therapies and beyond more challenging. Therapy will require individualization based on patient characteristics and preferences, while insurance coverage decisions and requirements may also impact the options that patients can access. Additional research regarding prognostic and predictive biomarkers is needed to help better identify optimal treatment approaches for specific patient populations. Multidisciplinary tumor boards will continue to play a critical role in guiding treatment selection for individual patients. Atezolizumab plus bevacizumab offers a promising new first-line therapeutic option for patients with advanced HCC, but more research is needed to optimize and individualize patient therapy.