First-line treatment options for unresectable HCC

Ghassan K. Abou-Alfa, MD, MBA: One might wonder why they chose lenvatinib. I would say this is an appropriate option. After all, it’s already approved by the FDA. This is based on the randomized clinical trial of the inferiority of sorafenib compared to lenvatinib. There is another choice: aezolizumab-bevacizumab. We may wonder why we choose 1 over the other. Mainly because there is a bit of excitement that a lot of us have when it comes to checkpoint inhibitors. It is imperative. We have 3+ atezolizumab-bevacizumab. Mainly due to the improvement in survival which is currently measured at over 19 months.

We must remember that despite the positive data with aitzolizumab-bevacizumab, many details continue to emerge from this study, which is called IMbrave150. Many of them at the AACR [American Association for Cancer Research] Annual meeting not too long ago, where the group first reported to us the assessment of patients based on the potential for anti-drug antibodies that may arise while the patient is being treated with aitzolizumab.

As we know, all patients who receive checkpoint inhibitors can develop anti-drug antibodies to this drug. We cannot say in advance who might receive the anti-drug antibody, but patients can develop the anti-drug antibody in 1 to 3 doses of treatment. We know of some drugs that have very limited anti-drug antibody potential; for example, durvalumab and pembrolizumab. But on the other hand, aezolizumab stands out.

This was confirmed by researchers at IMbrave150, who reported at the AACR annual meeting that 30% of patients in the study had anti-drug antibodies. What does it mean? It seems to me that the patients who tested negative for anti-drug antibodies, who did not develop anti-drug antibodies against this drug, did well. The hazard ratio was 0.5. It’s way better than we can think of, which is amazing. On the other hand, the 30% of patients positive for anti-drug antibodies had a relative risk of 0.96. In other words, the study compared aezolizumab plus bevacizumab-sorafenib, and ended up showing aezolizumab plus bevacizumab in these patients to be as effective as sorafenib.

You might wonder if I am giving all of these IV therapy or do I want to think about giving these patients just one pill? It continued to stabilize as a field. But there is no doubt that we can see that doctors as well as patients have different perspectives. Am I a risk taker? Should I really be on therapy and not worry about the potential anti-drug antibody? I am losing one option, which is the first line, because it might not work better than sorafenib. Perhaps I am subjecting myself to potential side effects, of which the greatest fear is the bleeding that may occur from bevacizumab. For this reason, the patient needs an endoscopy. Or should I play more carefully? There are still some effective therapies that can certainly have a benefit.

Transcription edited for clarity.


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