Tumor Treating Fields Concomitant with Sorafenib in Advanced Hepatocellular Cancer: Results of the HEPANOVA Phase II Study

SIMPLE SUMMARY: Advanced hepatocellular carcinoma (HCC) is an aggressive liver cancer with limited treatment options and poor prognosis. Tumor-Treating Fields (TTFields) are electric fields that disrupt cancer cell division and are approved for glioblastoma and mesothelioma treatment. Laboratory research and clinical data from other solid tumor types provided a rationale to investigate whether TTFields combined with a standard treatment (sorafenib) was effective and well tolerated in advanced HCC, with the aim of ultimately improving treatment for these patients. Overall, 27 patients with large tumors and advanced disease were included in this study. Results showed that TTFields with sorafenib reduced the tumor size in 9.5% of patients compared with 4.5% in other studies examining sorafenib alone and was well tolerated. Reduction of tumor size was even better in patients who received TTFields for ≥12 weeks (18%). Results support further investigation of TTFields used with sorafenib in a larger phase III clinical study. ABSTRACT: Advanced hepatocellular carcinoma (HCC) is an aggressive disease associated with poor prognosis. Tumor Treating Fields (TTFields) therapy is a non-invasive, loco-regional treatment approved for glioblastoma and malignant pleural mesothelioma. HCC preclinical and abdominal simulation data, together with clinical results in other solid tumors, provide a rationale for investigating TTFields with sorafenib in this patient population. HEPANOVA was a phase II, single arm, historical control study in adults with advanced HCC (NCT03606590). Patients received TTFields (150 kHz) for ≥18 h/day concomitant with sorafenib (400 mg BID). Imaging assessments occurred every 12 weeks until disease progression. The primary endpoint was the overall response rate (ORR). Safety was also evaluated. Patients (n = 27 enrolled; n = 21 evaluable) had a poor prognosis; >50% were Child–Turcotte–Pugh class B and >20% had a baseline Eastern Clinical Oncology Group performance status (ECOG PS) of 2. The ORR was higher, but not statistically significant, for TTFields/sorafenib vs. historical controls: 9.5% vs. 4.5% (p = 0.24), respectively; all responses were partial. Among patients (n = 11) with ≥12 weeks of TTFields/sorafenib, ORR was 18%. Common adverse events (AEs) were diarrhea (n = 15/27, 56%) and asthenia (n = 11/27, 40%). Overall, 19/27 (70%) patients had TTFields-related skin AEs; none were serious. TTFields/sorafenib improved response rates vs. historical controls in patients with advanced HCC, with no new safety concerns or related systemic toxicity.