Real-Life Analysis of Nivolumab in Patients With HCC Align With Clinical Trial Data

In an interview with Targeted Oncology, Maria Reig, MD, PhD, discussed the results from the retrospective analysis of patients with hepatocellular carcinoma treated with nivolumab in the real-life setting in Spain.

Maria Reig, MD, PhD

The importance of early diagnosis and appropriate management of hepatocellular carcinoma (HCC) was validated with safety data from a real-life cohort of patients receiving nivolumab (Opdivo), which appeared similar to data from clinical trials, despite the inclusion of patients in the second- and third-line settings.

Results presented at the the 13th Annual Conferences of the International Liver Cancer Association revealed hetergenity in the patterns of progression with treatments taken prior to nivolumab, like the combination of sorafenib (Nexavar) and regorafenib (Stivarga). In addition, grade 3 or higher adverse events (AEs) lead to treatment delays.

In the retrospective, observational, multicenter cohort, which included 118 patients from 10 institutions in Spain, the most common AEs included hepatitis C (57.1%) and hepatitis B (11.9%). At the last follow-up assessment, 25 patients remained alive, including 24 patients continuing to receive nivolumab, 1 patient who had discontinued, and 17 patients had died. One patient had discontinued therapy due to AEs while 17 patients discontinued due to disease progression.

Nivolumab was used as frontline therapy in 7 patients (16.7%), second-line in 20 patients (47.6%), and third-line in 15 patients (35.7%). For all patients receiving nivolumab in the second- or third-line settings, they received sorafenib (Nexavar) as their first-line treatment, and regorafenib (Stivarga) was used in the second-line setting for 86.7% of patients in the third-line group.

In the second-line arm, 10 patients discontinued nivolumab due to AE without radiologic progression. The median overall survival (OS) was 28.8 months (95% CI, 71.4-not estimable). Among patients receiving nivolumab in the third-line, 14 of 15 patients received therapy due to radiologic progression. The median OS was not calculated in the third-line arm.

A total of 18 patients presented with 27 AEs, which were mostly grade 1/2. Seven AEs were grade 3/4, and 1 AE was grade 5. Six of the 7 grade 3/4 AEs were immune-related. Corticosteroids were used for the management of 4 AEs, and treatment delays were required for the management of 4 AEs.

In an interview withTargeted Oncology, Maria Reig, MD, PhD, Hospital Clinic de Barcelona, discussed the results from the retrospective analysis of patients with HCC treated with nivolumab in the real-life setting in Spain.

TARGETED ONCOLOGY: What were the methods of design for your analysis?

Reig:We conducted a multicenter, retrospective cohort study at 10 centers in Spain. All centers were involved in clinical trial management also. We identified more than 100 patients that were treated with nivolumab. However, 42 of these patients were treated in a clinical practice, and we focused on this group of patients.

TARGETED ONCOLOGY: What were the findings from this?

Reig:The main result we observed was baseline characteristics of patients were quite similar to the clinical trials. However, the majority of patients were in the second- and third-line. Up until now, we don’t have data from third-line in clinical trials. [For this study], we had a specific group of patients with this profile.

The safety profile in this population was quite similar to what we have seen in clinical trials. However, the important point I would like to highlight from our study is the time off between finishing sorafenib treatment or regorafenib treatment and starting nivolumab treatment.

It is something we are addressing for the clinical point of view. We now have data in the third-line for nivolumab from a set of patients who had good outcomes. Our second point that we also observed is despite the fact that the follow-up of our cohorts is short with a median follow-up of around 6 months, the profile for AEs are mild or moderate in terms of toxicity. We believe that despite the fact that we do not have data to support OS for this specific group of patients who are not able to receive treatment that improves OS, we can consider this in this group of patients.

TARGETED ONCOLOGY: Would you like to elaborate more on the toxicity profile?

Reig:The number of patients we had was very limited, so we could not extrapolate our small numbers to this population. However, we had hepatitis and also the typical AEs that a nivolumab-treated patient would have.

I would like to point out that we only had 1 patient who presented with a prior history of [transplantation]. This patient had severe AEs, and the patient’s death was [determined to be] related to treatment. This is similar to the publication that does not allow patients with a prior history of transplant to receive nivolumab.

In our cohort, I can say that the profile was quite similar compared with what we have seen in the literature.

TARGETED ONCOLOGY: Are there any next steps planned?

Reig:This is difficult to answer because we do not have data based on OS. In our country, the only option to treat patients with nivolumab is if they do not have another option to improve OS. The next step now is working a combination trial of nivolumab plus a tyrosine kinase inhibitor at the same center we worked with on this project. We aim to identify the toxicity profile in terms of AEs with the combination therapy.


Da Fonesca LG, Minguez B, Sapena V, et al. Safety and outcome of hepatocellular carcinoma patients treated with nivolumab in real life hepato-oncology units. Poster presented at: 13th Annual Conferences of the International Liver Cancer Association; September 20-22, 2019; Chicago, IL. Abstract P-108.