Results of the KEYNOTE-045 trial show significantly longer survival in patients with advanced urothelial cancer who receive pembrolizumab after initial chemotherapy vs an alternative chemotherapy regimen. The results were presented at the ESMO 2017 Congress in Madrid.
These results confirm preliminary figures published earlier this year.
“[The results are] striking in the setting of urothelial cancer, which is highly lethal in the metastatic state,” said study investigator Ronald de Wit, MD, PhD, from Erasmus University Medical Center in Rotterdam, the Netherlands. “Pembrolizumab is the first agent to improve survival over chemotherapy in the second-line setting. Not all patients benefit from checkpoint inhibition, but a sizeable proportion of patients who respond have very durable responses, even well over one year.”
The phase 3 study involved patients whose urothelial cancer had recurred or progressed after platinum-based chemotherapy. They were randomly assigned to either the group that received the checkpoint inhibitor pembrolizumab or the investigator’s choice of paclitaxel, docetaxel, or vinflunine chemotherapy.
After 22.5 months of follow-up, results showed an approximately three-month improvement in overall survival (OS) in the group treated with pembrolizumab when compared with those receiving a second-line of chemotherapy (median 10.3 months vs. 7.4 months). An additional improvement was noted in the hazard ratio from 0.73 to 0.70 (P=0.0003) since the interim analysis.
Median progression-free survival (PFS) was not significantly different for either group (2.1 months for pembrolizumab vs 3.3).
“Some patients also benefit from second line chemotherapy, but these responses tend to be short-lived and toxicity typically prevents prolonged treatment, whereas pembrolizumab is well tolerated,” Dr. de Wit said.
He added that treatment-related adverse events of any grade occurred in 62% of pembrolizumab-treated patients, compared with 90.6% of those treated with chemotherapy.
In addition, quality of life (QOL) at week 15 showed better results in the pembrolizumab arm.
“Overall, the superior survival, better adverse event profile, and better QOL render pembrolizumab a new standard of care in the second line treatment of urothelial cell cancer,” he explained.
Maria De Santis, MD, from the University of Warwick, Coventry, and Queen Elizabeth Hospital, Cancer Centre, in Birmingham, UK, reports that these updated KEYNOTE-045 results are important, as they confirm the OS benefit of pembrolizumab compared to chemotherapy in platinum-pretreated patients.
“This is particularly important as the progression-free survival was not superior with pembrolizumab,” she said. “The PFS curve in this trial diverges late but then, after 6 months, it was again in favor of pembrolizumab. As PFS does not seem to be a good surrogate endpoint with pembrolizumab, a confirmed, robust OS benefit as shown in this updated analysis becomes increasingly important. The robustness of the OS benefit is confirmed by the even better HR of 0.70 in this update, compared to 0.73 at the first presentation of the data last year.”
She added that specific properties of this immunotherapy include a superior duration of response in the 20% of patients who do respond, and a favorable safety profile with a lower rate of severe side effects, compared to chemotherapy.
“Fewer patients on pembrolizumab had to discontinue treatment because of side effects compared to those on chemotherapy,” she said. “Severe immune related side effects were rare. This is of special importance as patients with urothelial cancer are usually older with multiple comorbidities.”
To read more about the study, click here.