Immunotherapy After Chemotherapy Could Slow Progression of Urothelial Cancer

The use of immunotherapy immediately after first-line chemotherapy treatment significantly slowed down the progression of cancer in patients with metastatic urothelial cancer, according to a recent study published in the Journal of Clinical Oncology.¹

Treatment with pembrolizumab via switch maintenance immunotherapy led to further objective responses among patients who achieved at least stable disease with chemotherapy, and prolonged progression-free survival among the patient population studied.

"This trial, along with another recent study testing a similar approach, bolster the use of switch maintenance treatment, which will likely become a standard of care for metastatic urothelial cancer, a disease characterized by a paucity of advances in decades," lead author Matthew Galsky, MD, said in a press release.²

This randomized double-blind phase 2 trial enrolled 108 patients who achieved at least stable disease on first-line platinum-based chemotherapy. The population was randomized into two groups: the pembrolizumab group (n = 55) and the placebo group (n = 53).

The objective response rate for the pembrolizumab group was 23% compared to 10% in the placebo group. Even more, progression-free survival was significantly longer (5.4 months; 95% CI, 3.1-7.3) for patients receiving pembrolizumab compared to patients in the placebo group (3.0 months; 95% CI, 2.7-5.5).

Median survival rate for the pembrolizumab group was 22 months (95% CI, 12.9, not reached) and 18.7 months (95% CI, 11.4, not reached) with placebo. Grade 3-4 treatment-related adverse effects occurred in 59% receiving pembrolizumab and 38% of patients receiving placebo.

“Here, we show that earlier use of PD-1 blockade with pembrolizumab, at the time of cessation of first-line chemotherapy, leads to additional objective responses and significantly prolongs progression-free survival compared with placebo,” wrote the researchers. “Importantly, in this placebo-controlled double-blind trial, the adverse event profile of pembrolizumab was similar to that reported in prior studies.”

The main limitation of the study centered around the relatively small sample size. Because of the specific requirements necessary for the population of patients, the sample was limited to 108 participants.

Despite first-line platinum-based chemotherapy treatment, the researchers explained that a majority of patients with metastatic urothelial cancer experience disease progression. Only 3 prospective studies have explored a switch maintenance strategy in patients with metastatic urothelial cancer.

Moving forward, the combined outcomes of the prospective trials investigating switch maintenance therapy have the power to shape the coming landscape of first-line treatment for metastatic urothelial cancer.

“Switch maintenance immune checkpoint blockade could potentially confer benefit largely for practical reasons,” wrote the researchers. “Earlier use of immune checkpoint blockade may simply increase the likelihood that individual patients are exposed to potentially active therapy.”

References:

1. Galsky M, Mortazavi A, Milowsky MI, et al. Randomized double-blind phase II study of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients with metastatic urothelial cancer. Journal of Clinical Oncology.

2. Immunotherapy treatment after chemotherapy significantly slows metastatic bladder cancer [news release]. Published April 9, 2020. https://www.eurekalert.org/pub_releases/2020-04/tmsh-ita040720.php. Accessed April 10, 2020.