The use of a personalized peptide vaccination (PPV) failed to improve progression-free survival (PFS) in patients with chemotherapy-resistant advanced urothelial bladder cancer, though overall survival (OS) was significantly better, according to a randomized, open-label, phase II trial.
Though urothelial bladder cancer is generally sensitive to chemotherapy, most patients will progress on platinum-based regimens and survival is limited, wrote study authors led by Masanori Noguchi, MD, PhD, of the Kurume University School of Medicine in Kurume, Japan. The researchers have developed a novel immunotherapeutic approach to second-line therapy, in which at most 4 human leukocyte antigen (HLA)-matched peptides are selected out of a pool of 31 peptides. The selection is based upon both HLA type and pre-existing host immunity prior to vaccination.
In this trial, 80 patients with progressive bladder cancer who had previously received platinum-based chemotherapy were randomized to either PPV plus best supportive care (BSC, 39 patients) or to BSC alone (41 patients). The results were published online ahead of print in Clinical Cancer Research.
The primary endpoint of the study was not met, with a median PFS of 2 months with PPV and 1.8 months with BSC. This yielded a hazard ratio for progression of 0.7 (95% confidence interval [CI], 0.4–1.2; P = .17).
At the time of data cutoff, 74% of the full cohort had died due to their disease. OS was in fact better with PPV, with a median of 7.9 months vs 4.1 months for BSC, for an HR of 0.58 (95% CI, 0.34–0.99; P = .049).
The most common adverse events in the PPV group were dermatologic reactions at injection sites in 91% of patients, abdominal pain in 34%, and increased creatinine levels in 34%. In the BSC group, abdominal pain (41%), peripheral edema (38%), and anemia (38%) were common. Almost all events were grades 1 or 2, and none of 32 grade 3 events were deemed related to treatment.
“This study is, to our knowledge, the first randomized phase II study investigating the efficacy of PPV treatment in patients with metastatic bladder cancer after failure of platinum-based regimens, and showed longer survival after cancer vaccination than BSC treatment,” the authors wrote.
They hypothesized that an advantage of PPV may be an ability to stimulate effector T cells for a faster and stronger immune response, as compared to a conventional peptide vaccine. “Because this study is a small scale of randomized clinical study, further investigation of PPV in advanced or metastatic urothelial cancer is warranted,” they concluded.