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Switch maintenance with PD-1-directed immunotherapy improved progression-free survival (PFS) for patients with metastatic urothelial cancer, a randomized phase II study found.

Among more than 100 patients with stable disease following first-line chemotherapy, those treated with maintenance pembrolizumab (Keytruda) achieved a median PFS of 5.4 months, compared with 3.4 months for those assigned to placebo (P=0.039), reported Matthew Galsky, MD, of the Tisch Cancer Institute at Mount Sinai in New York City, and colleagues.

Median overall survival (OS) showed a weak trend favoring the maintenance arm, at 22.0 months versus 18.7 months with placebo (HR 0.91, 95% CI 0.52-1.59), as described online in the .

Objective response rates were 23% in the pembrolizumab arm (including 9% with complete responses) and 10% in the placebo arm. Additionally, stable disease as best response was achieved in 35% versus 29%, respectively.

Among the 94 patients with archival tumor tissue, 30% in each arm had a PD-L1 combined positive score (CPS) of ≥10, but the researchers saw no significant differences in PFS or OS when examining outcomes by PD-L1 expression at various CPS cutoffs.

When PFS data from the study were presented at the 2019 American Society of Clinical Oncology meeting, Galsky told 口袋女优 that an effective switch-maintenance strategy in bladder cancer should include a therapy with good single-agent activity, should be reasonably well tolerated to minimize treatment burden, and should have a side effect profile that doesn't overlap with chemotherapy.

"If you give someone six cycles of chemotherapy and then give them another drug that can enhance those side effects, you're not accomplishing a whole lot," he said.

Whether anti-PD-1/L1 switch maintenance will prevail as standard of care for first-line bladder cancer is not entirely clear. The phase III JAVELIN Bladder 100 trial with maintenance avelumab (Bavencio) , demonstrating improved OS at an interim analysis, but a number of phase III trials are testing immunotherapy along with chemotherapy as first-line treatment.

One such trial, IMvigor130, added atezolizumab (Tecentriq) to platinum-gemcitabine chemotherapy, and showed a significant improvement in PFS over chemotherapy alone (8.2 vs 6.3 months, respectively) and a trend toward improved OS at an interim analysis (16.0 vs 13.4 months).

Galsky said these studies may indeed support immunotherapy as part of first-line treatment rather than as a maintenance therapy.

"There are potential benefits in terms of ease of use of that strategy, having a one-size-fits-all strategy," he said. "But there are some potential downsides to that strategy as well, including giving patients chemotherapy and immunotherapy for a period of six cycles where patients might only be benefiting from the chemotherapy."

But he added that in terms of patient selection, it remains unclear who will benefit from which particular regimen.

"Giving everything, we don't have to worry about that," said Galsky. "The results of those frontline studies and the results of the maintenance study ... ultimately all of that data will be put together to inform the best approaches to combination treatment versus sequential switch-maintenance treatment."

For the current study , 108 patients with metastatic bladder cancer whose disease had not progressed following six cycles of first-line chemotherapy were randomized 1:1 to either pembrolizumab (200 mg intravenously every 3 weeks for up to 2 years) or placebo. The study was conducted from 2015 to 2018.

Those receiving pembrolizumab underwent a median of eight treatment cycles, while the control group received six cycles of placebo. No major differences were seen in baseline characteristics between the two arms for age, race, or response to initial chemotherapy. Upon disease progression, patients in the placebo arm could cross over to receive pembrolizumab.

Grade 3/4 treatment-emergent toxicities occurred more frequently in the pembrolizumab arm (59% vs 38% with placebo), and included higher rates of dyspnea, fatigue, hematuria, hyperglycemia, increased liver enzymes, and urinary tract infection. In the pembrolizumab arm, 20% needed systemic steroid treatment due to immune-related events and there was one fatal case of hepatitis.

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