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Hello. I'm Ronald de Wit. I'm a medical oncologist from the Erasmus Medical Center Cancer Institute in the Netherlands, Rotterdam. And I was involved in the KEYNOTE-045 Study. The KEYNOTE-045 Study was a randomized phase three trial investigating the checkpoint inhibitor pembrolizumab versus investigator-choice of chemotherapy, vinflunine, docetaxel, or paclitaxel in patients with metastatic bladder cancer who had been exposed to one line of chemotherapy, platinum based, so, cisplatin, gemcitabine, or carboplatin gemcitabine or the M-fact regiment. Again, patients were randomized between pembrolizumab and chemotherapy.
Primary endpoint of the study was to show a survival benefit by the use of pembrolizumab versus second-line chemotherapy. The key endpoints of the study were, as I mentioned, to test for survival benefits and the study was positive. There was approximately a three month survival benefit by the use of pembrolizumab and there were also fewer side effects, fewer treatment-related adverse events. If you focus on three or four toxicities, it was 15% on pembrolizumab and it was 50% with the use of chemotherapy. So, the superior survival and the superior health-related side effects were in favor of pembrolizumab, rendering a new standard of treatment.
Now, equally important is to look at the health-related quality of life. So, what was also investigated in this study was quality of life by use and the C30 questionnaire as a complimentary investigation. The EQD5 was also investigated. The D5 is used mostly for health economic modeling. The C30 questionnaire is used for testing the functioning domains and symptom complaints. The poster that I presented at this ASCO meeting is really tailored on these C30 results.
Now, what was done in this study was that the questionnaires were completed electronically by the patients just before the new cycle and before they had discussed with the physicians about the results of their treatments and CT scans to avoid any bias. The questionnaires were completed every cycle during the first four cycles and then every other cycle afterwards.
Key endpoints for quality of life were the result by the end of Week 15 as well as time to deterioration of quality of life. Now, what was found in the study was that by Week 15 the quality of life had completely stabilized by the use of pembrolizumab whereas there was a robust and significant statistical worsening by the use of chemotherapy. The same was true with the Kaplan-Meier plot of the time to deterioration which was also statistically significant in favor of pembrolizumab. Hazard ratio of 1.70. We also looked at the results by the C-Status. What was found in patients whose disease worsened, there was only a very mild deterioration in quality of life in patients who received pembrolizumab, but there was a tremendous drop in quality of life in patients receiving chemotherapy.
Those patients who did well on pembrolizumab, there was an improved quality of life, whereas, even in responding patients to chemotherapy, there was a deterioration. So, taking everything together, all the measures that we did were statistically significant in favor of pembrolizumab. So, it's the survival benefit, it's the adverse event profile, and it is the quality of life that were all superior in terms of benefit by the use of pembrolizumab. I think that makes it a new standard of care in patients with bladder cancer that qualify for second-line treatment. That's my presentation. That is actually my poster.