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KEYNOTE-224: Second-Line Pembrolizumab

Insights From: Josep Llovet, MD, Mount Sinai School of Medicine; Riccardo Lencioni, MD, University of Miami Miller School of Medicine
Published: Wednesday, Feb 21, 2018



Transcript: 

Riccardo Lencioni, MD: The study presented on pembrolizumab is very interesting. We’re talking about a study conducted in the second-line setting with patients who progress under first-line sorafenib treatment still with compensated cirrhosis and a performance status of 0 or 1. These patients were offered pembrolizumab. The bottom line of this study is that there was a significant proportion of patients who had an objective response, something around 16% or so. What is very impressive is the duration of response. Basically, more than 90% of responders had a response in place for more than 6 months. This is, to some extent, similar to what has already been shown for nivolumab. There was a very high response rate, in the range of 20%, for nivolumab and a similar duration of response.

Now, the key question here is, who are the patients who will truly benefit from such a durable response? Clearly, with these immune-oncology drugs, responses are dramatic and sustained. So, it’s something unprecedented in oncology in general. The question is still open on, what about the nonresponders? How we can boost the response rate and eventually the survival for these patients? Studies are ongoing, and time will tell. Certainly, combining different agents has been shown to be beneficial in other cancers. It’s probably should be one of the main areas for research also in HCC.

Josep Llovet, MD: It is important to understand that pembrolizumab is working in HCC, because currently there are several studies combing TKIs, particularly regorafenib and lenvatinib, with pembrolizumab. There are also other TKIs—for instance, cabozantinib—in combination with nivolumab. So, we need to understand these drugs that, as standalones, already provide benefit and, therefore, sense which of the TKIs are the most beneficial to combine with immunotherapies.

Transcript Edited for Clarity 
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Transcript: 

Riccardo Lencioni, MD: The study presented on pembrolizumab is very interesting. We’re talking about a study conducted in the second-line setting with patients who progress under first-line sorafenib treatment still with compensated cirrhosis and a performance status of 0 or 1. These patients were offered pembrolizumab. The bottom line of this study is that there was a significant proportion of patients who had an objective response, something around 16% or so. What is very impressive is the duration of response. Basically, more than 90% of responders had a response in place for more than 6 months. This is, to some extent, similar to what has already been shown for nivolumab. There was a very high response rate, in the range of 20%, for nivolumab and a similar duration of response.

Now, the key question here is, who are the patients who will truly benefit from such a durable response? Clearly, with these immune-oncology drugs, responses are dramatic and sustained. So, it’s something unprecedented in oncology in general. The question is still open on, what about the nonresponders? How we can boost the response rate and eventually the survival for these patients? Studies are ongoing, and time will tell. Certainly, combining different agents has been shown to be beneficial in other cancers. It’s probably should be one of the main areas for research also in HCC.

Josep Llovet, MD: It is important to understand that pembrolizumab is working in HCC, because currently there are several studies combing TKIs, particularly regorafenib and lenvatinib, with pembrolizumab. There are also other TKIs—for instance, cabozantinib—in combination with nivolumab. So, we need to understand these drugs that, as standalones, already provide benefit and, therefore, sense which of the TKIs are the most beneficial to combine with immunotherapies.

Transcript Edited for Clarity 
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