Updated Phase 3 Trial Results Continue to Favor Keytruda as Second-Line Treatment for Bladder Cancer

Updated Phase 3 Trial Results Continue to Favor Keytruda as Second-Line Treatment for Bladder Cancer

Patients with advanced urothelial cancer who received one prior line of chemotherapy live significantly longer when given Keytruda (pembrolizumab) as a second-line treatment instead of the standard of care chemotherapy, according to the findings of a recent study.

The findings come from the Phase 3 KEYNOTE-045 trial (NCT02256436), recently presented at the European Society for Medical Oncology (EMSO) 2017 Congress in Madrid.

The poster, “Pembrolizumab (pembro) versus paclitaxel, docetaxel, or vinflunine for recurrent, advanced urothelial cancer (UC): mature results from the phase 3 KEYNOTE-045 trial,” was presented by study investigator Ronald de Wit of Erasmus University Medical Center in Rotterdam, the Netherlands.

Urothelial cancer, which typically occurs in the renal system, is highly lethal in its metastatic state. The standard first-line treatment is platinum-based combination chemotherapy, after which there is no internationally accepted standard of care.

KEYNOTE-045 was designed to test the effectiveness of Keytruda compared with chemotherapy — Taxol (paclitaxel), Taxotere (docetaxel), or Javlor (vinflunine) — as a second-line treatment for patients who had recurred or progressed after platinum-based chemotherapy.

In the study, 272 patients received Keytruda, which was developed by Merck, while 270 received one of the chemotherapies.

After 22.5 months of follow-up, patients in the Keytruda group lived nearly three months longer than those in the control group, or 10.3 months vs. 7.4 months, respectively.

No significant differences in time to disease progression or death from any cause were observed (2.1 months vs. 3.3 months, respectively), but treatment-related adverse effects were much less frequent in Keytruda-treated patients compared to those treated with chemotherapy: 62% vs. 90.6%, respectively. Keytruda also resulted in an improved quality of life (QOL) at week 15, the study’s authors noted.

“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,” de Wit said in a press release.

Based on interim findings of KEYNOTE-045 published earlier this year, the U.S. Food and Drug Administration and the European Medicines Agency have already approved Keytruda as a second-line treatment for advanced urothelial carcinoma patients who received prior platinum-based chemotherapy.

“Fewer patients on pembrolizumab had to discontinue treatment because of side effects compared to those on chemotherapy. Severe immune related side effects were rare. This is of special importance as patients with urothelial cancer are usually older with multiple comorbidities,” said Maria De Santis of the University of Warwick, Coventry, and Queen Elizabeth Hospital Cancer Center in Birmingham, U.K., commenting on the study.

“These updated KEYNOTE-045 results are important as they confirm the overall survival benefit of pembrolizumab compared to chemotherapy (investigator’s choice) in platinum-pretreated patients,” she concluded.