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The use of single tremelimumab (Imjudo) and regular interval durvalumab (Imfinzi; STRIDE regimen) in patients with unresectable hepatocellular carcinoma (HCC) showed manageable and low-grade immune-mediated adverse events (imAEs), according to findings presented at the American Society of Clinical Oncology (ASCO) annual meeting.

In this exclusive 番茄社区 video, Jun Gong, MD, from the Samuel Oschin Cancer Center at Cedars-Sinai in Los Angeles, explained the study design and clinical significance of his team's phase III .

Following is a transcript of his remarks:

So just a little bit of a background. The HIMALAYA trial was a phase III randomized study, enrolling patients with untreated advanced hepatocellular carcinoma, or HCC, to 1:1:1 randomization, to a regimen called STRIDE, which is a combination of tremelimumab, which is an anti-CTLA-4 antibody, and durvalumab, which is an anti-PD-[L1] inhibitor versus another arm of durvalumab, which is an anti-PD-[L1].

These two first groups are considered immune checkpoint inhibitors -- these are immune therapies. And essentially they were compared against the standard of care at that time, which is sorafenib [Nexavar], which is an oral tyrosine kinase inhibitor. The initial study results from the HIMALAYA phase III trial showed that durvalumab and tremelimumab, which we call the STRIDE regimen for short, showed a superior overall survival benefit to sorafenib, really positioning this combination as a new first-line standard for HCC.

Now at ASCO 2023, we've provided an update, and we decided to explore the relationship between side effects that are created by the immune response as a result of the immune checkpoint inhibitor therapy. We call these immune-mediated adverse events or imAEs for short, and to see if there was any relationship between having the presence of imAEs to immune therapy and whether that was associated with improvements and efficacy.

The reason for this being because for other tumor types in the past, we've noticed that certain patients who experience imAEs may actually do better than those who don't have imAEs. So we decided to explore this relationship.

Now for this analysis, there were 388 patients that were treated with the combination immunotherapy STRIDE, and there were 388 patients treated with durvalumab monotherapy combination. What were the most common imAEs to begin with? They were hypothyroidism, hyperthyroidism, diarrhea, and rashes.

What we found out was that the occurrence of imAEs tended to occur early in the treatment immunotherapy, within 3 months. However, fortunately most of them were very low grade, very managed, with few dose delays in dose reductions because of this imAEs.

What we then found out was with the STRIDE regimen, in those who experienced imAEs, overall survival was almost 23 months compared to those who did not experience any imAEs; their overall survival was 13 months. And if you looked at landmark analyses about 6, 12, 24, and 36 months, patients who experienced imAEs had consistently higher survival across these landmarks with the STRIDE regimen.

With respect to the durvalumab monotherapy arm, it was less clear whether the relationship with imAEs improved efficacy or not. But the takeaway statement was, regardless of imAEs, immune therapy did better than sorafenib. But within the immunotherapy combination on STRIDE, if you had imAEs, that actually may be an early biomarker that the therapy is working and that they may have improved outcomes compared to those without imAEs.

And I think our study also reinforces the importance that these imAEs occur early, but fortunately, they're very manageable, they're safe, they're low grade. This is one of the breakthrough results at ASCO from Cedar-Sinai.

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