Hello. I'm David Kerr, professor of cancer medicine at University of Oxford. I have spent a considerable amount of time in China, where I'm a visiting professor at a number of leading institutions. This is an important connection for me, which I built up in my days as the president of ESMO. I have many friends and senior colleagues scattered throughout China. They always recognize that the quality of cancer medicine in China has improved significantly over the past decade, as has the quality of trials. I mention this because I'd like to talk about the results of the KEYNOTE-224 study that's been published recently in Lancet Oncology.[1] China hosts about 50% of the world's total population of hepatocellular carcinoma. In the KEYNOTE study, a conventional dose of pembrolizumab, 200 mg IV every 3 weeks, was used in a cohort of patients who had failed or progressed on treatment with sorafenib, so [pembrolizumab was used as] a second-line treatment. The study has some really interesting results. The overall response rate was around 17% of the 104 patients that they treated in this single-arm, nonrandomized phase 2 trial, with [an additional] 44% of patients having disease stabilization. These are highly meaningful results in this difficult group of patients. The drug seemed to be pretty well tolerated. The grade 3 toxicity rate was about a quarter of patients, and there didn't seem to be any viral flares. There were a couple of cases of autoimmune hepatitis, but by and large, the drug was pretty well tolerated in this often difficult-to-treat patient population. There was a significant element of selection going on, but nevertheless, I think these are interesting results. Of course, we await the definitive results of randomized phase 3 studies, but I think this shows significant promise. Clearly, one other approach in hepatoma would be to consider combinations of pembrolizumab with other agents, which may help to augment the immune responsiveness. There are always two sides to this coin. One, of course, is the effect of pembrolizumab as an immune checkpoint inhibitor on the immune system's capacity to recognize and destroy tumor cells. If we could increase the immunogenicity of the tumors themselves, increasing antigen expression, upregulating MHC [major histocompatibility complex], and so on, then these are the sorts of drug combinations that might be effective and worth looking at in this common and often rapidly fatal disease. This study provides an important step forward, and phase 3 trial results are awaited with interest, but I think it gives us a clue or cues to how we should be thinking about randomized phase 2 trials looking at some thoughtful combinations of immune checkpoint inhibitors with other immunomodulatory drugs. Thanks for listening, and for my Chinese friends, I would say, "Xiè xie," which is "Thank you." [I’m always interested in] any comments that you would like to make or post. Thanks a lot. Goodbye.
KEYNOTE-224: Pembrolizumab Active and Well Tolerated in Pretreated Advanced Hepatocellular Carcinoma
Hello. I'm David Kerr, professor of cancer medicine at University of Oxford. I have spent a considerable amount of time in China, where I'm a visiting professor at a number of leading institutions. This is an important connection for me, which I built up in my days as the president of ESMO. I have many friends and senior colleagues scattered throughout China. They always recognize that the quality of cancer medicine in China has improved significantly over the past decade, as has the quality of trials. I mention this because I'd like to talk about the results of the KEYNOTE-224 study that's been published recently in Lancet Oncology.[1] China hosts about 50% of the world's total population of hepatocellular carcinoma. In the KEYNOTE study, a conventional dose of pembrolizumab, 200 mg IV every 3 weeks, was used in a cohort of patients who had failed or progressed on treatment with sorafenib, so [pembrolizumab was used as] a second-line treatment. The study has some really interesting results. The overall response rate was around 17% of the 104 patients that they treated in this single-arm, nonrandomized phase 2 trial, with [an additional] 44% of patients having disease stabilization. These are highly meaningful results in this difficult group of patients. The drug seemed to be pretty well tolerated. The grade 3 toxicity rate was about a quarter of patients, and there didn't seem to be any viral flares. There were a couple of cases of autoimmune hepatitis, but by and large, the drug was pretty well tolerated in this often difficult-to-treat patient population. There was a significant element of selection going on, but nevertheless, I think these are interesting results. Of course, we await the definitive results of randomized phase 3 studies, but I think this shows significant promise. Clearly, one other approach in hepatoma would be to consider combinations of pembrolizumab with other agents, which may help to augment the immune responsiveness. There are always two sides to this coin. One, of course, is the effect of pembrolizumab as an immune checkpoint inhibitor on the immune system's capacity to recognize and destroy tumor cells. If we could increase the immunogenicity of the tumors themselves, increasing antigen expression, upregulating MHC [major histocompatibility complex], and so on, then these are the sorts of drug combinations that might be effective and worth looking at in this common and often rapidly fatal disease. This study provides an important step forward, and phase 3 trial results are awaited with interest, but I think it gives us a clue or cues to how we should be thinking about randomized phase 2 trials looking at some thoughtful combinations of immune checkpoint inhibitors with other immunomodulatory drugs. Thanks for listening, and for my Chinese friends, I would say, "Xiè xie," which is "Thank you." [I’m always interested in] any comments that you would like to make or post. Thanks a lot. Goodbye.
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