skip to Main Content

Nivolumab and pembrolizumab display anti-tumour activity and adequate tolerance in ‘real-world’ studies in carcinoma

ILC 2019: ‘Real-world’ studies report the activity and safety profiles of nivolumab and pembrolizumab to be in line with those observed in hepatocellular carcinoma phase II clinical trials


13 April 2019, Vienna, Austria: ‘Real-world’ studies conducted in Spain, Austria and Germany have reported activity and safety data for nivolumab and pembrolizumab in the treatment of hepatocellular carcinoma (HCC) that, according to the investigators, are in line with those observed in the phase II clinical trials. The studies reported today at The International Liver Congress™ 2019 in Vienna, Austria, found that these two immunotherapies were active and well tolerated even in heavily pretreated individuals and those with Child–Pugh class B (moderate) liver disease.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with more than half a million people worldwide diagnosed with the condition each year.1 Treatment options for early-stage HCC include ablative procedures, surgical resection, and liver transplantation and other options such as locoregional treatments and systemic therapies improve the overall survival of patients with intermediated or advanced HCC.2 Immunotherapy with the checkpoint inhibitors, nivolumab and pembrolizumab, could represent a relatively new approach to the treatment of HCC.3–6 Nivolumab and Pembrolizumab have a conditional approval in the USA for the second-line treatment of individuals with HCC who have previously received a tyrosine kinase inhibitor.5 The details of the Phase 3 study of pembrolizumab in the second-line treatment of advanced HCC will be presened soon, but it was recently announced that the primary endpoints were not met.7

Results from ‘real-world’ studies with immune checkpoint inhibitors in the treatment of HCC have only recently begun to emerge, 8,9 and more data are needed.2 In the first ‘real-world’ study presented today, the records of 42 individuals with HCC who received nivolumab outside clinical trials in Spain. In this cohort, almost all patients received nivolumb as second-line (n=20, 47.6%) or third-line (n=15, 35.7%).

Of the 20 individuals treated with nivolumab as a second-line therapy (60% Child-Pugh A; 40% Child-Pugh B), five had discontinued their first-line treatment (sorafenib) due to adverse events without radiological progression. In this cohort, the median follow-up since the start of first-line treatment was 13.5 months (interquartile range [IQR] 6.9–27.1) and overall survival (OS) was 28.8 months (95% CI 9.4–non-estimable), respectively. All except one of the 14 individuals treated with nivolumab in the third-line setting (85.7% Child-Pugh A) received nivolumab due to radiological progression. In this cohort, the median follow-up since the start of first-line treatment was 21.3 months (IQR 15.6–24.4) and the OS was not calculated due to an insufficient follow-up and number of events.

Fifteen (46.8%) individuals reported 25 AEs, of which five were Grade 3–4 and only one was Grade 5 (rejection after liver transplantation). Corticosteroids were required for the management of AEs in five individuals (15.6%).

‘This study suggests that the safety profile of nivolumab when used in clinical practice is in line with that reported in clinical trials despite including patients outside of clinical trials,’ said Dr Leonardo Gomes da Fonseca from the BCLC group at the Hospital Clinic of Barcelona, Spain. ‘The survival data must be interpreted bearing in mind that some patients had not progressed prior to receiving nivolumab and the overall patterns of progression were heterogeneous.’

The second study retrospectively evaluated 65 individuals who received nivolumab (n=34) or pembrolizumab (n=31) between 2015 and 2018 at six centres in Austria and Germany. Of these, 32 (49%) were Child-Pugh A, 28 (43%) were Child-Pugh B, and five (8%) were Child-Pugh C. Immunotherapy was used as first-, second-, third-, or fourth-line treatment in nine (14%), 27 (42%), 26 (40%), and three (5%) individuals, respectively. Fifty-four individuals had at least one follow-up imaging report and were evaluable for radiological response.

The overall response and disease control rates reported in this study were 12% and 49%, respectively. Thirty-five (54%) individuals had radiological disease progression and 36 (55%) died during follow-up. The median time to progression was 5.5 months (95% CI 3.5, 7.4); median progression-free survival was 4.6 months (95% CI 3.0, 6.2), and median OS was 11.0 months (95% CI 8.2, 13.8). The most common adverse events were infections (n=7), rash (n=6), pruritus (n=3), fatigue (n=3), diarrhoea (n=3), and hepatitis (n=3). The outcomes and safety results were comparable between Child-Pugh A and B patients; however, median overall survival was shorter in Child-Pugh B patients (16.7 vs 8.6 months; p=0.065).

‘Immunotherapy with nivolumab or pembrolizumab was well tolerated in patients with advanced HCC, including those with Child-Pugh stage B disease and those who had been heavily pretreated,’ said Dr Matthias Pinter from the Medical University of Vienna, Austria. ‘Efficacy was comparable to that reported in Phase 2 studies.’


About The International Liver Congress™

This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ 2019 will take place from 10­–14 April 2019 at the Reed Messe Wien Congress and Exhibition Center, Vienna, Austria.

About The European Association for the Study of the Liver (EASL)

Since its foundation in 1966, this not-for-profit organization has grown to over 4,000 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European association with international influence, and with an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.


For more information, please contact the ILC Press Office at:

Onsite location reference

Session title: ‘Liver cancer –  Systemic treatment  and immunotherapy’

Time, date and location of session: 08:15–08:30, 13 April 2019, Hall C2

Presenter: Leonardo Gomes da Fonseca, Spain

Abstract: A multicentric study on real-life impact of nivolumab in patients with hepatocellular carcinoma (PS-137)

Session title: ‘Liver cancer –  Systemic treatment  and immunotherapy’

Time, date and location of session: 08:30–08:45, 13 April 2019, Hall C2

Presenter: Matthias Pinter, Austria

Abstract: PD-1 targeted immunotherapy in advanced hepatocellular carcinoma: Efficacy and safety data from an international multicenter real-world cohort (PS-138)

Author disclosures

Leonardo Gomes da Fonseca has received travel grant, lecture and consulting fees from Bayer and travel grants from Ipsen.

Matthias Pinter served as consultant for Bayer, BMS, Eisai, Ipsen, and Lilly, and received travel support from Bayer, and speaking fees from Bayer, BMS, and MSD. He is also an investigator for Bayer, BMS, and Lilly.


  1. Population fact sheets. Available at: Accessed: March 2019
  2. Forner A, et al. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–14.
  3. Iñarrairaegui M, et al. Clin Cancer Res. 2018;24(7):1518–24.
  4. El-Khoueiry AB, et al Lancet. 2017;389(10088):2492–502.
  5. Finkelmeier F, et al. Nivolumab for the treatment of hepatocellular carcinoma. Expert Rev Anticancer Ther. 2018;18(12):1169–75.
  6. Mody K, Abou-Alfa GK. Systemic therapy for advanced hepatocellular carcinoma in an evolving landscape. Curr Treat Options Oncol. 2019;20(2):3.
  7. Merck Newsroom. Merck Provides Update on KEYNOTE-240, a Phase 3 Study of KEYTRUDA® (pembrolizumab) in Previously Treated Patients with Advanced Hepatocellular Carcinoma [Press release]. 2019. Available at:
  8. Finkelmeier F, et al. Feasibility and safety of nivolumab in advanced hepatocellular carcinoma: real-life experience from three German centers. J Cancer Res Clin Oncol. 2019;145(1):253–9.
  9. Yoon SE, et al. Real-world data on nivolumab treatment in Asian patients with advanced hepatocellular carcinoma. Ann Oncol. 2018;29(Suppl 8):viii205–70.