Refractory Urothelial Cancer & Mucosal Melanoma Patients May Benefit From Pembrolizumab

Pembrolizumab demonstrated efficacy as second-line therapy for advanced urothelial cancer and as a possible treatment for patients with advanced mucosal melanoma

medwireNews: Pembrolizumab may extend overall survival (OS) in patients with platinum-refractory advanced urothelial cancer and shows activity against advanced mucosal melanoma, suggests research reported at the 2017 European Cancer Congress in Amsterdam, the Netherlands.

Andrea Necchi, from the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, presented a late-breaking abstract for the KEYNOTE-045 trial of second-line treatment with the anti-programmed death 1 (PD-1) antibody versus the investigator’s choice of paclitaxel, docetaxel or vinflunine in urothelial cancer patients unselected for programmed death-ligand 1 (PD-L1) expression.

After a median of 9.0 months, 18.4% of the 270 patients given pembrolizumab remained on treatment versus 1.2% of the 272 patients given chemotherapy.

Median OS was significantly longer with pembrolizumab than chemotherapy, at a median of 10.3 versus 7.4 months and a hazard ratio (HR) of 0.73.

Median progression-free survival (PFS) was comparable in the pembrolizumab and chemotherapy groups, at 2.1 versus 3.3 months, but pembrolizumab offered a superior objective response rate (ORR), at 21.1% versus 11.4%, giving a significant treatment difference of 9.6%.

The median duration of response to pembrolizumab has not been reached, the researchers note, compared with a median of 4.3 months with chemotherapy.

“We estimate that almost twice as many pembrolizumab responders will respond to the therapy for at least one year: 68% versus 35%”, Andrea Necchi commented in a press release.

Pembrolizumab was also associated with a lower rate of any-grade treatment-related adverse events (61 vs 90%) and grade 3–5 events (15 vs 49%).

“This is important because this patient population tends to be mostly elderly patients who have many other illnesses and health conditions as well”, the presenting author emphasized.

“These results support the use of pembrolizumab as the new standard of care for advanced bladder cancer.”

Positive pembrolizumab results were also reported for 84 patients with advanced mucosal melanoma who had participated in the KEYNOTE-001, -002 and -006 trials, 90% of whom had received at least one prior treatment. Seventy percent of the patients had PD-L1-positive tumours.

The ORR was 19% and the disease control rate (DCR) was 31%, with a median PFS of 2.8 months and a median OS of 11.3 months. For the 16 patients who responded to treatment, median time to response was 12.4 weeks and median duration of response was 27.6 months.

Furthermore, 39% of the patients had previously received the CTLA-4 inhibitor ipilimumab and in these patients the ORR was 15%, the DCR was 27% and median duration of response was 27.6 months.

“Our results show that patients benefited from pembrolizumab regardless of whether or not they had been pre-treated with ipilimumab”, presenting author Marcus Butler, from the Princess Margaret Cancer Centre in Toronto, Ontario, Canada told the press.

While noting the need for further investigation to understand why response rates were lower for mucosal melanoma than that reported for other subtypes, he added: “These findings suggest that mucosal melanoma patients should be offered immunotherapy as standard of care and not excluded.”


Presented at ECCO2017 European Cancer Congress; Amsterdam, the Netherlands: 27–30 January

medwireNews ( ) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2017