medwireNews: Switch maintenance pembrolizumab prolongs progression-free survival (PFS) versus placebo in patients with metastatic urothelial cancer (UC) who have achieved at least stable disease with first-line platinum-based chemotherapy, phase 2 study data show.
Writing in the Journal of Clinical Oncology, Matthew Galsky (Mount Sinai School of Medicine, New York, USA) and colleagues explain that switch maintenance is a treatment approach in which immune checkpoint blockade is initiated immediately after cessation of first-line platinum-based chemotherapy.
To test its efficacy in metastatic UC, Galsky and team randomly assigned 108 patients to receive switch maintenance pembrolizumab 200 mg intravenously once every 3 weeks (n=55) or placebo (n=53) for up to 24 months.
After a median 12.9 months of follow-up, PFS was significantly longer with maintenance pembrolizumab than with placebo at 5.4 versus 3.0 months and a hazard ratio of 0.65 for disease progression or death.
After excluding patients with a complete radiographic response to first-line chemotherapy, the objective response rate (ORR) was 23% among 43 participants who received pembrolizumab and 10% among the 42 who received placebo. Complete response rates were 9% and 0%, respectively.
Median overall survival (OS) was similar between the two arms, at 22 months with pembrolizumab and 18.7 months with placebo, but the researchers point out that this was a secondary endpoint and the study was not adequately powered to detect a survival improvement.
In all, 27 patients in the placebo group crossed over to receive pembrolizumab after disease progression. The median durations of PFS and OS from crossover among these patients were 2.7 and 15.8 months, respectively, and the ORR was 22%.
Galsky et al say that the pembrolizumab adverse event [AE] profile “was similar to that reported in prior studies,” with 20% of patients who received this treatment needing systemic steroid treatment for immune-related AEs. One patient in the pembrolizumab arm died due to treatment-related hepatitis.
The investigators also note that, despite follow-up every 3 weeks, 13% of patients randomly assigned to receive placebo died before receiving any second-line systemic therapy, which they say is “a potential concern that has been highlighted in prior observational studies” and underscores “at least one of the potential rationales underlying a switch maintenance approach with an active non–cross-resistant therapeutic class.”
Galsky and co-authors conclude: “Additional ongoing randomized phase III trials, including the recently reported IMvigor130 study are exploring even earlier use of PD-1/PD-L1 blockade in metastatic urothelial cancer, administered concurrently with first-line chemotherapy and continuing as maintenance.”
“Ultimately, the outcomes of [these] trials will together shape the near-term landscape of first-line treatment of metastatic urothelial cancer, a disease state characterized by a paucity of advances in decades.”
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