GU cancer

Checkpoint inhibition extending life in bladder cancer

An update from KEYNOTE-045 has confirmed the overall survival benefit of pembrolizumab compared to second-line chemotherapy in patients with advanced urothelial cancer.

The research, presented at the ESMO 2017 Congress, found overall survival increased from 7.4 months with chemotherapy to 10.3 months with pembrolizumab after more than 22 months of follow-up.

The 18-month overall survival rate was 33.2% with the checkpoint inhibitor against 19.7% with the investigators’ choice of second-line chemotherapy including paclitaxel, docetaxel or vinflunine.

The new findings, including no significant difference in progression-free survival between treatment arms, are similar to those from the 14-month follow-up of KEYNOTE-045 published earlier this year.

Researcher Dr Ronald de Wit, from Rotterdam’s Erasmus University Medical Center in the Netherlands, said the findings were ‘striking in the setting of urothelial cancer, which is highly lethal in the metastatic state’.

“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.”

He said while some patients also benefit from second-line chemotherapy, their responses tended to be short-lived and toxicity typically prevented prolonged treatment.

The study reported treatment-related adverse events of any grade in 62.0% of pembrolizumab-treated patients compared to 90.6% of patients treated with chemotherapy. Higher-grade adverse events occurred in 16.5% and 50.2% of patients respectively.

“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 concluded.

The phase 3 study comprised 542 patients whose urothelial cancer had recurred or progressed after platinum-based chemotherapy.

The survival advantage from pembrolizumab was independent of patient age, liver metastases, haemoglobin, visceral disease and choice of chemotherapeutic agent.


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