medwireNews: A prespecified third analysis has confirmed initial findings of the KEYNOTE-045 trial of pembrolizumab in patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.
The results were presented at the 2017 annual meeting of the American Society of Clinical Oncology, held in Chicago, Illinois, USA, by Dean Bajorin (Memorial Sloan Kettering Cancer Center, New York, USA).
“Pembrolizumab is the first immunotherapy to demonstrate superior survival over chemotherapy in patients with advanced urothelial carcinoma after failure of platinum-based chemotherapy”, he told the meeting.
Bajorin explained that the second interim analysis findings for overall survival (OS), determined after a median of 14 months, resulted in US FDA approval for pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma.
The latest findings, from data cutoff in January 2017, gave a median OS of 10.3 months for the 270 patients randomly assigned to receive pembrolizumab 200 mg every 3 weeks. This was significantly longer than the 7.4 months achieved by the 272 patients given a paclitaxel, docetaxel or vinflunine regimen.
Pembrolizumab-treated patients had a higher OS rate at 12 months (44.4 vs 30.2%) and 18 months (36.1 vs 20.5%) than their chemotherapy counterparts, and this OS benefit occurred across subgroups of patients based on factors such as primary tumor site, pattern of metastases, or programmed cell death ligand 1 (PD-L1) combined positive score.
Progression-free survival did not significantly differ between the pembrolizumab and chemotherapy arms of the trial (2.1 vs 3.3 months) but the overall objective response rate was higher with the immunotherapy agent (21.1 vs 11.0%). This was also true for the rates of complete response (7.8 vs 2.9%) and partial response (13.3 vs 8.1%).
“Responses were more durable with pembrolizumab versus chemotherapy,” Bajorin said, citing an unreached median duration in the pembrolizumab versus 4.4 months for chemotherapy. A response lasting at least 12 months was reported in 69% and 36% of the arms, respectively,
In addition, rates of both any-grade treatment-related side effects (61.3 vs 90.2%), and grade 3 or above side effects (16.5 vs 49.8%) were lower with pembrolizumab than chemotherapy. Immune-related adverse events associated with pembrolizumab included hypothyroidism, pneumonitis and hyperthyroidism but these were mainly grade 1–2 events.
“Pembrolizumab should be considered a standard of care for these patients, supported by level 1 evidence that now shows superiority of survival and toxicity”, Bajorin concluded.
“Based on these data, the FDA provided full approval of pembrolizumab for the treatment of advanced urothelial carcinoma after failure of platinum-based therapy without the need for PD-L1 staining,” he added.
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