木瓜直播

The optimal second-line treatment for patients with advanced hepatocellular carcinoma (HCC) previously treated with immune checkpoint inhibitors has not been established. A study presented at the recent American Society of Clinical Oncology (ASCO) meeting evaluated the activity of regorafenib (Stivarga) plus pembrolizumab (Keytruda) in patients with advanced HCC who progressed on a prior immune checkpoint inhibitor.

In this exclusive 木瓜直播 video, investigator Anthony B. El-Khoueiry, MD, from the Keck School of Medicine of the University of Southern California in Los Angeles, describes the background and results of the .

Following is a transcript of his remarks:

So I'm happy to share with you the results from the study combining pembrolizumab and regorafenib in second-line treatment of hepatocellular carcinoma after treatment with immune checkpoint inhibitors.

So what's unique about this study is that it is one of the first prospective studies to ask the question about what could be a good therapy after progression on immunotherapy [IO] in first line. So to set the stage, immunotherapy combinations are now the standard of care treatment for first line hepatocellular carcinoma. The second-line treatment at the moment remains empiric. Meaning what we are doing is we are taking the TKIs [tyrosine kinase inhibitors] such as sorafenib [Nexavar], lenvatinib [Lenvima], cabozantinib [Cabometyx], regorafenib, and using them in some random order in second line and beyond. And we are really extrapolating from data that was actually derived in the post-sorafenib days for cabozantinib and regorafenib, or we are using sorafenib and lenvatinib, which actually were developed as first-line agents, now using them in second line post-IO. All of this based on no prospective data, at least no level 1 evidence.

So again, hence the importance of this study [is] to begin to ask the question prospectively, what could be effective [in] second-line and beyond regimens? Now the focus of this study is to really ask whether the continuation of anti-PD1 therapy with the addition of a TKI -- regorafenib in this case -- will achieve a response rate that is promising to take forward. So the assumption or the goal here was that we would have a response rate of 30% to 35% with the combination assuming a historical response rate of 20% or less.

So the study was designed as a prospective phase II level study with two cohorts. Cohort one was patients who had prior atezolizumab [Tecentriq]/bevacizumab [Avastin]; cohort two were patients who had any immune checkpoint inhibitor-based therapy. It could be single agent; it could be other combinations.

When we look at the objective response rate, the primary endpoint, we see that it was roughly in the 5% range for cohort one, post-[atezolizumab/bevacizumab], and around 11%, or 10% to 11%, for the cohort two, which is post-any IO combination or single agent. So that fell short of our target of 30% to 35%. So it's modest response rates. The disease control rate was about 54% for cohort one, 74% or so for cohort two. So we do see some stabilization of the cancer. We see a subset of patients responding with durable responses, but certainly the activity seems to be within the range of what you would expect to see with tyrosine kinase inhibitors like regorafenib.

Of note, what I didn't mention is the pembrolizumab/regorafenib combination when evaluated in first-line therapy had a response rate of 31%. So it is an active combination, but here in the post-IO setting, it doesn't show the same level of activity.

So the combination has modest activity. Patients should not be continuing on anti-PD1 therapy in second line with the addition of another agent unless it's on a trial. More studies need to be done in this space.

Another important observation we made. It's an exploratory analysis where we looked at the patients who had [pembrolizumab]/regorafenib in first line, and looked at their tumor profile and tumor microenvironment. And the patients in this study who got [pembrolizumab/regorafenib] post-IO, you can clearly see that in the post-IO population there are definitely signs of T-regulatory lymphocyte upregulation and a T cell exhaustion signature. So the immune microenvironment post-IO seems to be altered quite a bit, which hopefully should guide further investigations in the future.

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