Pembrolizumab shows promise for advanced bladder cancer

Issue: July 25, 2015

CHICAGO — Pembrolizumab demonstrated encouraging antitumor activity and OS rates in patients with advanced urothelial cancer, according to study results presented at the ASCO Annual Meeting.

Patients with PD-L1 expression achieved a particularly high response rate with pembrolizumab, results showed.

"Bladder cancer currently represents around 4.5% of cancers diagnosed, and chemotherapy is the only effective treatment for the disease,” Elizabeth R. Plimack, MD, MS, associate professor of medical oncology and director of genitourinary clinical research at Fox Chase Cancer Center, told HemOnc Today. “There are issues associated with chemotherapy, including well-known toxicities and the fact that even when it works very well, dosing cannot continue forever because problems inevitably arise. We have been looking for an alternative to chemotherapy for decades in bladder cancer.”

Pembrolizumab (Keytruda, Merck) — an anti–PD-1 antibody — previously exhibited efficacy and acceptable toxicity in patients with recurrent or metastatic PD-L1–positive urothelial cancer, according to study background.

Plimack and colleagues evaluated data from 33 patients (median age, 70 years; range, 44-85) with recurrent, metastatic or persistent urothelial cancer of the bladder, renal pelvis, ureter or urethra. Thirty-three percent of patients underwent three or more previous treatments, and all had an ECOG performance score of 0 to 1.

Researchers assessed PD-L1 expression in baseline tumor samples and defined PD-L1 positivity as staining in the stroma or in at least 1% of tumor cells.

Patients received a 10-mg/kg dose of pembrolizumab every 2 weeks until complete response, disease progression or unacceptable toxicity.

Median follow-up was 15 months (range, 0.6-20).

Researchers observed an overall response rate (ORR) of 28% (95% CI, 12.7-47.2) among 28 evaluable patients. Three patients achieved complete response, five patients achieved partial response and three patients achieved stable disease. The median time to response was 9 weeks (range, 7.7-55.9).

Forty-eight percent (95% CI, 29.4-67.5) of patients experienced progressive disease.

Researchers observed a median OS of 12.7 months (95% CI, 5-NR). Fifty-two percent of patients remained alive at 12 months.

Researchers observed a median PFS of 2 months (95% CI, 1.7-4), and 19.1% of patients achieved 12-month PFS.

PD-L1–positive tumor status served as a strong predictor for antitumor response. The ORR among patients with PD-L1–positive tumor cells was 33% (95% CI, 13-59), compared with 9% (95% CI, 0-41) among patients with PD-L1–negative tumors.

Among patients with PD-L1–positive tumor-associated inflammatory cells, researchers observed an ORR of 29% (95% CI, 13-51), compared with 0% (95% CI, 0-60) among patients with PD-L1–negative inflammatory cells.

Any-grade adverse events occurred in 60% of the patient population. The most frequently reported adverse events included fatigue (n = 6), peripheral edema (n = 4) and nausea (n = 3).

Grade 3 or higher adverse events occurred in 15% of the patient population and included dehydration, hypercalcemia, myalgia and thrombocytopenia (n = 1 for all).

One patient discontinued treatment due to a treatment-related adverse event.

“We are seeing over half of patients alive at 1 year [post-treatment], which is something we rarely saw in pre-treated patients with chemotherapy,” Plimack said. "Pembrolizumab … empowers the immune system to go after the tumor. I think it is going to make a real difference [in bladder cancer].” – by Cameron Kelsall and Alexandra Todak

Reference:

Plimack ER, et al. Abstract 4502. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

For more information:

Elizabeth R. Plimack, MD, MS, can be reached at Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111; email: elizabeth.plimack@fccc.edu.

Disclosure: Plimack reports research funding from and advisory roles with Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Dendreon, Genentech, GlaxoSmithKline, Lilly, Merck, Novartis and Pfizer. Please see the abstract for a list of all other researchers’ relevant financial disclosures.