Optimization of the selection of first line TKIs for Advanced HCC

Josep M. Llovet, MD, PhD: If you chose TKI [tyrosine kinase inhibitor] whatever the contraindications to a desert map in this patient, given the aggressiveness of the disease, that is to say the invasion of the segmental portal vein, an infiltrating tumor is an indirect sign aggression and AFP [alpha-fetoprotein] of 9000 ng / mL. What is your decision in terms of unique frontline TKI?

Andrea Casadei Gardini, doctor of medicine: I would choose lenvatinib for this patient. Normally I prescribe a combination. I chose it because lenvatinib and sorafenib are 2 very different drugs. Lenvatinib is a response to the disease: our patient has a high invasion of alpha-fetoproteins and it filters down to liver damage. Our response to this patient is to prolong overall survival. The difference between the 2 TKIs is the response and the adverse events. My patients have demonstrated tolerance to lenvatinib. There are fewer skin reactions and we have more hypertension. I usually prescribe 5 mg of Norvasc [amlodipine] if there is hypertension during treatment. Another problem with lenvatinib is anoxia, but we don’t have a case in our hospital [San Raffaele Research Hospital]. It has better response and better tolerability, so in this case I choose lenvatinib for our patient.

Josep M. Llovet, MD, PhD: This week there was a press release for the HIMALAYA trial. The final analysis compares durvalumab-tremelimumab with sorafenib one-on-one. After several months, the analysis in the press release showed positive results for the primary endpoint, which is OS [overall survival] superiority. This is the first I / O [immuno-oncology]–I / O combination in HCC [hepatocellular carcinoma] that can change the management landscape. In the decision-making process, we need OS, progression-free survival, objective response, adverse events, and patient-reported outcomes. What impact does this have on frontline management?

Stephen L. Chan, MD: This study will be very important, perhaps a landmark study. The HIMALAYA trial is a phase 3 trial with a robust sample size – it is close to 1200 patients – with 3 arms. The control arm is sorafenib. One experimental arm is durvalumab as monotherapy, and the other experimental arm is a dose of tremelimumab and durvalumab. The main objective of this study was to compare tremelimumab-durvalumab vs sorafenib. I was impressed not only with the positivity of the clinical trial and the endpoint, but also with the clinically significant difference.

In the press release, we mentioned statistical significance and clinical significance. My interpretation of clinical significance means improvement in OS, of at least 1 to 2 months. He also suggested that they had successfully demonstrated non-inferiority between durvalumab and sorafenib. CheckMate 459 did not demonstrate this. The key message from this study is that we have a safer and more efficient I / O / O combination. It also suggests that durvalumab I / O as monotherapy may be an alternative option to sorafenib. We need to read the full data, which will probably be at ESMO [European Society for Medical Oncology Congress] Next year.

Josep M. Llovet, MD, PhD: Thank you.

Transcription edited for clarity

Martin E. Berry