Novel First-Line Immunotherapy Approaches in Advanced HCC

Panelists close out their discussion on first-line treatment options for advanced HCC with a review of single-agent and combination immunotherapy approaches.


Josep Llovet, MD: Andrea, is there room for single-agent checkpoint inhibitors in frontline [therapy]?

Andrea Casadei-Gardini, MD: Yes. That’s a good question because with very old patients or patients with a particular comorbidity, it’s not possible to prescribe the combo. It’s very difficult to identify a patient for whom I’d prescribe only monotherapy with I/O [immuno-oncology]. In the HIMALAYA trial, the combo is well tolerated, and it’s very difficult to identify a patient for whom I’d prescribe only monotherapy.

Josep Llovet, MD: Any different opinion?

Arndt Vogel, MD: The data are very consistent. We’ve seen atezolizumab with very consistent efficacy data of about 16 months. Still, those patients you’re describing aren’t part of the clinical trial. They might be suitable. We talked a little about Child-Pugh B, so this is something we could discuss. My experience with atezolizumab-bevacizumab in Child-Pugh B patients, and even advanced Child-Pugh A patients, isn’t convincing. In line with the post hoc analysis from the IMbrave150 study and the HIMALAYA study, the efficacy of durvalumab and durvalumab-tremelimumab were very consistent in … and the CheckMate040 study also showed good data for Child-Pugh B patients. Maybe in patients with Child-Pugh B, it could be something to consider.

Amit Singal, MD: Child-Pugh is a heterogeneous group, so I don’t think we can say all Child-Pugh B patients. [In Child-Pugh B], 7 points is very different from 9. Going back to your initial question about which patients I’d consider for single-agent I/O, I think that well-selected Child-Pugh B patients is a population you could consider it for. The CheckMate040 data, for example, showed tolerance. But it’s a tough patient population. Once again, I don’t think we can say all Child-Pugh B patients are very well selected.

Josep Llovet, MD: Before moving to second-line [therapy], I want to give you an impression about the trials that have been reported in ESMO [European Society for Medical Oncology]. If I recall, there are 3 trials. LEAP-002 is comparing lenvatinib-pembrolizumab with a median survival of 21.5 vs lenvatinib alone at 19 months; the P value was 0.022. The press-specified 0.018. The trial is negative, so this regimen is out of the picture in the sense that it will unfortunately not be approved.

Then there was the camrelizumab-rivoceranib trial, which was reported positive. This trial was mostly conducted in Asia—17% of the centers were out of Asia. This trial was positive against sorafenib, and the median survival was 22 months if I recall, and with sorafenib it was around 15 months. The results are strong, but let’s see what happens with the regulatory agencies. This is the first time we have this challenge, with 95% of patients in the West, but they were positive trials. Let’s see what happens.

The last trial you mentioned was for tislelizumab, a checkpoint inhibitor that is noninferior compared with sorafenib. What’s your take very briefly about these 3 trials? What are the implications?

Arndt Vogel, MD: The combination trial of camrelizumab [and rivoceranib], or apatinib has a clear survival benefit of 6 months. We have to acknowledge that only 17% of patients are from outside Asia, which is a concern. We shouldn’t talk only about overall survival [because] you have efficacy, toxicity, adverse effects, profile liver function, and all these points. The survival is great, but what you haven’t mentioned is that we have hypertoxicity in 30% of cases. We have a different adverse effect profile for the TKI [tyrosine kinase inhibitor], which is more VEGFR2 directed. We’re not used to that in the West. We have to start learning to work with this drug. Nevertheless, it’s 22 months, which is a new bar. It’s a positive study. We have to wait and see with the regulatory agencies, but we also need to see more data. It’s too early. We have to see whether it’s strong enough to replace atezolizumab-bevacizumab, which I don’t think will be the case.

Josep Llovet, MD: To add to what you’re saying, grade 3/4 treatment-related adverse events were 80%.

Arndt Vogel, MD: Go ahead.

Amit Singal, MD: When we talk about Asian vs non-Asian trials, 1 of the key differences is that when you have Asian trials, you have many more patients who have underlying hepatitis B. The liver function is usually much more preserved if not noncirrhotic. When you think of HCC [hepatocellular carcinoma], this is a disease within a disease. This type of thing makes a marked difference, in terms of not only demographics but also prognosis. That’s why we remark on this Asian versus non-Asian thing. It’s not just a matter of saying, “Was it evaluated in the patients we see in clinical practice?” It can really drive these marked survival differences. The survival may be vastly overestimated with what we would expect to see in a Western patient population. That’s where Western data are going to be very critical.

Arndt Vogel, MD: They will do post hoc analysis and subgroup analysis, but there are very few patients.

Amit Singal, MD: If you have few patients and wide confidence intervals, then you don’t know where this falls.

Transcript edited for clarity.

Related Videos
Pamela L. Kunz, MD, associate professor, internal medicine (medical oncology), Yale School of Medicine; director, Center for Gastrointestinal (GI) Cancers, chief, GI Medical Oncology, Smilow Cancer Hospital, Yale Cancer Center
Suneel Kamath, MD
Suneel Kamath, MD
Jennifer R. Eads, MD, physician lead, GI Cancer Research, director, National Clinical Trials Network, Abramson Cancer Center, University of Pennsylvania, associate professor, clinical medicine (hematology-oncology), Penn Medicine, Perelman Center for Advanced Medicine
Olivia Aranha, MD, PhD
Michael Iglesia, MD, PhD
Petros Grivas, MD, PhD; and Chandler Park, MD, MSc, FACP
Arndt Vogel, MD
Daniel M. Halperin, MD, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Haeseong Park, MD, MPH