Prospective Findings of TTFields/Sorafenib in Advanced HCC May Warrant a Randomized Study

The final analysis of the phase 2 HEPANOVA EF-30 study (NCT03606590) aimed to give a prospective demonstration of the safety and efficacy of adding tumor treating fields (TTFields) to tislelizumab (BGB-A317) and sorafenib (Nexavar) to treat patients with advanced hepatocellular carcinoma (HCC). Based on the results reported thus far, investigators led by Chris Verslype, MD, PhD, hypothesized that the study will yield positive results.

HEPANOVA EF-30 enrolled 27 patients with unersectable HCC who were able to receive systemic therapy with sorafenib after failure of loco-regional therapy options. To be eligible, patients were required to have an ECOG performance status of 0 to 2, Barcelona clinic liver cancer (BCLC) stage 0-C disease, Child-Turcotte-Pugh (CTP) score between 5 and 8 points, and have measurable disease.

Those treated received sorafenib 400 mg given as 2 200 mg tablets along with TTFields of 150 kHz for 18 hours per day until local disease progression per RECIST. The primary end point of the study was overall response rate (ORR), and the secondary end points were in-field control rate, 12-month progression-free survival (PFS) rate, 1-year overall survival (OS) rate, and the incidence of adverse events (AEs).

According to a presentation given as part of the European Society of Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2021, the ORR observed was 9.5%. In terms of the secondary end point, the PFS was 5.8 months, and there was a 1-year OS rate of 30%. The safety analysis showed that 67% of patients had grade 1 or 2 TTFields-related toxicity, and the same AE was grade 3 for 1 patient. Full safety and efficacy analyses in the study are ongoing.

In an interview with Targeted Oncology following the ESMO World Congress on Gastrointestinal Cancer 2021, HEPANOVA EF-30 investigator, Eleni Gikka, MD, a radiation oncologist at the University Medical Center Freiburg, provided insight into the use of TTFields in combination with standard of care therapy for patients with advanced HCC.

TARGETED ONCOLOGY: Can you explain the needs for new treatment options for this patient population?

Gika: Until now, patients with HCC were treated with sorafenib, but bot with the new data from the IMbrave150 study (NCT03434379). Immunotherapies are the treatment of choice, specifically atezolizumab and bevacizumab. But still, the results are not that good concerning the response rates and OS.

Prior to the IMbrave150 study, we conducted a study in order to see the toxicity and efficacy of TTFields in this patient population. Several studies are currently ongoing with TTFields, and we know from malignancies such as glioblastoma or pleural mesothelioma, which are very aggressive tumors, that TTFields have shown high efficacy. The therapy has led to OS benefits in this patient population, which is very important because we didn't have good results with this treatment for many decades.

Can you explain this treatment modality and why it may be a good option for patients with advanced HCC?

TTFields are an antimitotic treatment, which is originally applied with electric fields, which are applied non-invasively in the region of the tumor with a portable medical device. The patient can carry this the whole day and the treatment should be applied 18 hours per day, but the patient can sleep with it, and it doesn't reduce the quality of life for those patients.

What were the results you presented during the recent ESMO World Congress on Gastrointestinal Cancer 2021?

As I mentioned, we applied the TTFields in these patients concurrently with sorafenib. We had a patient population that was in a higher ECOG score and the higher child-Turcotte-pugh

Twenty-two percent of the group had an ECOG score of 2. Patients received TTFields for a median duration of 10 weeks, and the patient's got autopilot sorafenib for a median duration for of 9 weeks.

The efficacy results were good. We had the median PFS of 5.8 months and time to progression of 8.9 months. The 1-year survival rate was not so good, of course, because the study population was not similar to previous studies with sorafenib. There's always been bevacizumab, and still, we could see that the efficacy was nevertheless good. Of course, this was not a randomized study, and we see also that was that we had no serious adverse events are no toxicity problems in the combination with sorafenib.

What is the key takeaway from this study?

I think the first step, and the reason why we did this study is to see if we can combine these 2 treatments for these patients and if we could get any positive results. I think this was something that we did show in this study. The next step is, of course, to do a randomized study and probably with the new standard of care, which is immunotherapy.

_Reference:

_{Gikka E, Grosu A, Mazarulla T, et al. O-16 HEPANOVA: Final efficacy and safety results from a phase 2 study of Tumor Treating Fields (TTFields, 150 kHz) concomitant with sorafenib in advanced hepatocellular carcinoma. Ann Oncol. 2021;32(suppl 3):S225. doi: 10.1016/j.annonc.2021.05.808}