Daniel P. Petrylak, MD
Pembrolizumab (Keytruda) was approved in May 2017 for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
The approval was based on the KEYNOTE-045 study, in which the median overall survival was 10.3 months with pembrolizumab versus 7.4 months with chemotherapy (HR, 0.70; P
<.001), which consisted of paclitaxel, docetaxel, or vinflunine.
“These patients have prolonged durable responses and that is what is really driving the survival benefit in the situation,” said Daniel P. Petrylak, MD.
In an interview with OncLive
at the 2017 ASCO Annual Meeting, Petrylak, professor of Medicine and Urology, co-director, Signal Transduction Research Program, Yale School of Medicine, discussed the KEYNOTE-045 results and the next steps with pembrolizumab in urothelial carcinoma.
OncLive: Can you provide an overview of KEYNOTE-045?
KEYNOTE-045 is a randomized trial that compared pembrolizumab to a dealer’s choice chemotherapy in patients with urothelial cancer who had been previously treated with either carboplatin or cisplatin-based chemotherapy regimens. The trial was important since it was the first to demonstrate a survival benefit in favor of checkpoint inhibitor therapy compared to chemotherapy.
The chemotherapy arm saw a survival benefit of about 7 months whereas the checkpoint inhibition arm was about 10 months. That is a significant difference and is clinically meaningful when compared to other checkpoint inhibitor regimens. There is a proportion of patients, around 25% who do extremely well. These patients have prolonged durable responses and that is what is really driving the survival benefit in the situation.
How do you anticipate the approval of pembrolizumab in this setting will affect the treatment landscape, given the explosion in immunotherapies?
The trouble is, at this point, we have nothing that differentiates one checkpoint inhibitor from another. We don’t yet know the role of efficacy. There was a phase III trial that was just released in the press with atezolizumab (Tecentriq). We have not seen the full data yet, making it difficult to say what the exact results are, but Genentech announced that they did not meet their primary endpoint. What we need is a careful analysis of that trial before we make any major conclusions. Nonetheless, pembrolizumab has shown a survival benefit in the phase III trial, whereas other checkpoint inhibitors have been approved based on accelerated approval parameters.
Since the side effects and response rates are similar, the only distinguishable feature between these drugs is the schedule. There are some Q2 week, Q3 week, and Q4 week drugs. The real question is how comfortable is the physician or the patient going 4 weeks without being seen. It is important to have a good staff to be sure that the patient is not developing side effects. In my opinion, the Q3 week schedule is the most beneficial, since it’s right in the middle. However, Q2 weeks may also have an advantage, as well.