So I don’t know how many patients in this trial did not have access to pembrolizumab if they were not a part of the trial but if these are patients who would have had access to pembrolizumab if they were not a part of the trial but got randomised to chemotherapy simply because they were a part of this trial then that is quite unethical. These patients would never receive chemotherapy in the real world if they have access to. These are patients with PD-L1 more than 50%. Now, this was done in Europe, Asia and the rest of the world, not in North America, but I’m quite unhappy with the control arm again. It’s called the EMPOWER-Lung1 trial of cemiplimab versus chemo. Interestingly, there was one more trial of a checkpoint inhibitor presented at ESMO. Having said that, lorlatinib is not exactly a very safe drug either – we saw high rates of increased triglycerides, hyperlipidemia, hypercholesterolemia, oedema and also there are some important effects in terms of cognition decline, so that should be kept in mind. So again I think that this just provides us with one more option but it cannot be called a standard of care because the control arm was not the standard of care. Lorlatinib is certainly one more option to have but it’s not a cheap drug either. So I don’t think this changes our decision making much. Again, there are some issues with the control arm here because the standard of care for ALK positive lung cancer patients now is not crizotinib, it is alectinib, but in this trial the control arm was crizotinib. It’s a phase III randomised controlled trial of lorlatinib versus crizotinib for ALK positive lung cancer patients. We discussed about ADAURA, the other trial that was presented was the CROWN trial. Now, moving on to other trials, new trials, that were presented at ESMO, first let’s see some trials from lung cancer. We don’t know overall survival data yet but quality of life data was presented at ESMO 2020 and quality of life has been shown to improve with pembrolizumab versus chemo so I think that pembrolizumab should be the standard of care for first line treatment of metastatic colorectal cancer patients now. I had also expected overall survival to improve. We saw an impressive benefit in PFS, nearly doubling of PFS with pembrolizumab versus chemo and at the time I had said that we also need to see what the effect is on quality of life. The other trial that we discussed at ASCO as well is the KEYNOTE-177 trial of pembrolizumab versus chemotherapy in MSI high colorectal cancer patients. This looks so good because the trial has been stopped early. We should also keep in mind that for this type of trials that have been stopped early for early signal of benefit usually the benefits are exaggerated so the hazard ratio, the true hazard ratio, is probably not as good. So if they have not received osimertinib at the time of relapse then that is another way in which the results may be skewed. The other thing is about we also don’t know how many patients in the control arm got osimertinib at the time of relapse because osimertinib is the standard of care in first line treatment now for EGFR mutation positive patients. So if this CNS effect of osimertinib is predominantly on patients who did not get MRI of the brain at baseline then that could skew the results. There are a couple of points to highlight: we have the New England Journal publication of the ADAURA trial now but still we don’t know the percentage of patients that got MRI of the brain at baseline. So, my take-home message from ADAURA does not change yet, OS data is still immature so we need to follow up on OS. However, having said that, I had expected osimertinib to improve CNS relapse because of such good management of overall DFS benefit, it wouldn’t have happened without benefit in CNS. We knew that there was significant benefit in disease free survival from ASCO 2020 but at ESMO they also presented the benefit in terms of disease free survival benefit in CNS relapse and it was quite impressive as well. There were a couple of updates on those trials at the ESMO 2020 meeting.įirst we are talking about the ADAURA trial in lung cancer. Before discussing about other trials first let me discuss about a couple of trials that were presented at ASCO and I had already summarised them in my ASCO round-up video. Hello everyone, this is Dr Bishal Gyawali from Queen’s University, Kingston, Canada and I’m back with you all today to provide a round-up of the major trials and results from the ESMO 2020 virtual meeting.
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