- Data from the pivotal KEYNOTE-045 study showing improved survival in patients taking Merck & Co's Keytruda for advanced bladder was presented at the Society for Immunotherapy of Cancer (SITC) annual meeting over the weekend.
- In the study, which was halted early for efficacy, there was a significant improvement in overall survival, with a one year survival of 43.9% from Keytruda in the overall study group, compared with 30.7% in the chemotherapy group. In the patients who express PD-L1, the one year rate was 39.8% with Keytruda, compared with 26.9% with chemotherapy.
- There was a 27% reduction in the risk of death in patients treated with Keytruda rather than conventional chemotherapy (p=0.0022), and a 43% reduction in the patients who expressed PD-L1 (p=0.0048).
The checkpoint inhibitor space is a competitive one, with Merck & Co, Roche and Bristol-Myers Squibb duking it out for a handful of different indications. While bladder cancer is a smaller market than the lung cancer arena they are currently sparring over, good results here will put Merck's Keytruda (pembrolizumab) in a position to face up to Roche's Tecentriq (atezolizumab). Tecentriq got both first- and second-line approval for the indication in mid-2016, irrespective of PD-L1 status, and has three Phase 3 trials in bladder cancer ongoing.
KEYNOTE-045 is the first study to show a survival benefit for a PD-1/PD-L1 agent in bladder cancer. The positive results presented at SITC on all patients with advanced bladder (urothelial) cancer previously treated with platinum-containing chemotherapy, not just those that were expressing PD-L1, will give Merck just that extra edge of confidence.
"The improved overall survival for patients receiving Keytruda in this trial are clinically significant and could impact how physicians consider treating patients with previously treated advanced urothelial cancer," said Roger Dansey, SVP of late-stage oncology development at Merck Research Laboratories. "These data add to the growing body of evidence from our clinical development program for Keytruda in a range of cancers, including advanced urothelial cancer."
Opdivo (nivolumab) is still in the running in bladder cancer too, with priority review status and a review date set for March 7, 2017. Bristol-Myers Squibb presented data at SITC as well, looking at its combination of Opdivo (nivolumab) and Yervoy (ipilimumab) in patients with locally advanced or metastatic urothelial carcinoma, a common form of advanced bladder cancer, previously treated with platinum-based therapy. The preliminary data from the open-label Phase 1/2 trial, known as CheckMate-032, showed an objective response rate of 38.5% for the Opdivo 1 mg/kg plus Yervoy 3 mg/kg, compared with 26.0% for the Opdivo 3 mg/kg plus Yervoy 1 mg/kg.
According to the company, these results support further development of the combination in metastatic urothelial carcinoma in platinum refractory patients.