Taletrectinib superior to crizotinib in ROS1-positive non-small cell lung cancer
Dr Misako Nagasaka - UCI School of Medicine, Irvine, USA
This study basically compares taletrectinib, which is a new drug for ROS1 non-small cell lung cancer, to the older generation drug called crizotinib. Because there are no head-to-head comparison data available just yet, we did an analysis called MAIC – matching adjusted indirect comparison.
What was the study design?
This study is called MAIC, matching adjusted indirect comparison, and how this is done is by basically accumulating data from separate studies and comparing them, the data, adjusting for some variables. For the data for taletrectineb patients who were TKI naïve from the TRUST-I and TRUST-II studies were utilised, and for the crizotinib data patients from PROFILE 1001 were utilised. This was a study that ultimately led to the approval of crizotinib in ROS1 non-small cell lung cancer, so these patients were essentially all TKI naïve. Using the data from these patients there were variables that the target population was adjusted to and these matching variables included things like gender, ECOG performance status, smoking history, histologic classification and also the number of previous lines of therapy.
What were the results?
Basically the results showed that when we compare taletrectinib to crizotinib using this matching adjusted indirect comparison analysis we found the superiority of taletrectinib over crizotinib for efficacy – things like overall response rate. For example, taletrectinib before adjustment the objective response rate was 88.8%, after adjustment it was 90.1%, and crizotinib the objective response rate was 71.1%. Results were also similar for progression free survival and overall survival, indicating that there was a 52% reduction in the risk of disease progression or death with taletrectinib when compared to crizotinib. Also for overall survival there was a 66% reduction in the risk of death when taletrectinib was used versus crizotinib.
The other important factor of the study was the fact that we were able to do some comparisons on the safety data. Basically, the grade 3 or higher treatment-related adverse events were similar with taletrectinib or crizotinib and with crizotinib there were more vision disorders seen and the rates of dizziness and dyschezia between taletrectinib and crizotinib were similar.
What do you think is the significance of these results?
As you know, ROS1-positive non-small cell lung cancer accounts for a very small fraction of the whole non-small cell lung cancer population, perhaps 1-2% at best. That means that this is a rare disease and it’s going to be very difficult to demonstrate clinical trials in a large number of samples in a quick fashion. So it’s going to take longer to carry out these studies because it’s a rare population and right now, given the lack of direct comparison data from phase III studies, analyses such as MAIC really help us understand the efficacy and safety in comparison to older generation drugs in this field.
Is there anything else you would like to add?
While phase III direct head-to-head comparison studies should be encouraged, I think we should also understand the importance of doing matched adjusted indirect comparison analysis and other types of real-world analysis to make sure that we have comprehensive data available and be able to offer patients great options while we are waiting for the phase III direct head-to-head comparison data.
