The major point is that the US FDA and the regulators are requiring randomised studies with any newer therapies in order to provide a new standard of care in this patient population. It may have a huge impact because the non-CIS patient population is a consistent patient population, pretty well defined by the guidelines. How can the study results impact clinical practice? This is important data and these data are coupled with the confirmed safety outcomes that are in line with the safety outcome already provided in various disease settings with monotherapy with pembrolizumab, including cohort A of the study, with stable quality of life parameters over time, meaning that the combination of safety and efficacy in the all-comers and in the PD-L1 positive and negative subgroups may justify a potential expansion of the indication of pembrolizumab besides the CIS population, also including the BCG unresponsive papillary tumours. So a signal for numerically higher maintained responses with PD-L1 positive tumours but, at the same time, the main message providing the efficacy and confirming the efficacy of pembrolizumab regardless, mainly, of PD-L1 expression.
If we look at the subgroup analysis by PD-L1 expression, stratified by CPS combined positive score expression of PD-L1 based on the DAKO platform, we realised that patients with PD-L1 high tumours benefitted with a twelve-month disease-free survival rate of 54% while for PD-L1 negative tumours the rate of the twelve-month disease-free survival for high-risk disease recurrence was 39%. The overall findings from this cohort, which included 132 patients, were related to the fact that the primary endpoint consisting of the twelve-month disease-free survival for high-risk disease recurrence was 43% in the ITT population. This is a very special patient population for which we don’t have any standard of care, any robust standard of care, and for which there is limited opportunity for inclusion in clinical trials. The cohort B of the study, which is the focus of this meeting presentation, is related to the patients with BCG unresponsive non-CIS tumours, so papillary tumours, pTa or pT1, unresponsive to BCG. Cohort A of the study, of the KEYNOTE-057, already provided data on the activity of pembrolizumab monotherapy in patients with carcinoma in situ components with or without papillary tumours and resulted in 40% response, complete response, at three months with about one-third of the responses maintained over time long-term, and resulted in the US FDA approval of pembrolizumab monotherapy in patients with BCG unresponsive CIS population. So, for this patient population there is still an unmet medical need. The KEYNOTE-057 study is a multicentre phase II study investigating multiple cohorts of patients with high-risk non-muscle invasive bladder cancer whose disease has failed, has relapsed, after adequate BCG therapy.
#Keynote 057 update
I will present at this congress the update related to the cohort B of the KEYNOTE-057 study.
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