Utilization of pembrolizumab in high-risk NMIBC appears similar in real-world vs clinical trial settings


Time on treatment with pembrolizumab (Keytruda) in patients with high-risk non-muscle invasive bladder cancer (NMIBC) was similar in the real world, vs the clinical trial setting of the KEYNOTE-057 study, at 6.8 months vs 4.2 months, respectively, according to a poster presentation at the Society of Urologic Oncology 23rd Annual Meeting.1

“This is the first real-world study evaluating pembrolizumab utilization among patients who had high-risk, [Bacillus Calmette-Guerin (BCG)]-unresponsive NMIBC,” the study authors wrote in the poster.

After a median follow-up of 10.6 months (range, 0.8-26.3), real-world median time on pembrolizumab treatment was 6.8 months (95% CI, 5.7-9.0), compared with 4.2 months in the KEYNOTE-057 trial. In total, 1001 infusions of the agent were administered in the real-world setting, with the majority at a dose of 200 mg (91%) every 3 weeks (80%).

Moreover, the real-world on-treatment rate was 78% at 3 months (95% CI, 71%-86%), 39% at 9 months (95% CI, 31%-50%), and 19% at 18 months (95% CI, 12%-30%), while the clinical trial on-treatment rate was just 41% at 3 months.

The study authors noted that response rates and reasons for pembrolizumab treatment discontinuation were unavailable; however, they found that 78% of patients in the real-world setting remained on monotherapy treatment with pembrolizumab at 3 months and 54% at 6 months.

After real-world treatment with pembrolizumab, 30% of patients received subsequent treatment, including 9 patients who underwent radical cystectomy (median time from pembrolizumab initiation, 9.2 months). The median time to next treatment after pembrolizumab initiation was 18.7 months. Lastly, the real-world median treatment-free interval was 13.0 months.

Retrospective claims-based analysis background

“In 2022, there will be an estimated 81,180 new cases of bladder cancer in the United States, making bladder cancer the fourth most common cancer among men,” the study authors wrote, adding that despite the fact that the current standard of care for high-risk NMIBC is transurethral resection with subsequent BCG immunotherapy, responses are not often durable, “with about half of cases recurring within 1 year.”

In turn, the FDA approved pembrolizumab for the treatment of BCG-unresponsive, high-risk NMIBC, with carcinoma in situ, with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy in January 2020, based on data from the KEYNOTE-057 study. However, no studies have evaluated the real-world utilization of the agent in this setting.

Therefore, the study authors aimed to compare real-world use, vs pembrolizumab utilization in the KEYNOTE-057 trial, to describe patient demographics and clinical characteristics, real-world time on treatment (length of time between the first and last administration dates before discontinuation), real-world time to next treatment initiation (interval between time from pembrolizumab until cystectomy, radiation, or systemic therapy), real-world treatment-free interval (the interval between the end of pembrolizumab therapy and the start of subsequent therapy), and on-treatment rates.

To be eligible to be included in the retrospective claims-based analysis, patients had to be 18 years or older; have bladder cancer diagnosis codes within Optum’s de-identified Clinformatics Data Mart Database; have initiated pembrolizumab monotherapy between January 1, 2020, and December 31, 2021; have continuous enrollment during the 6-month pre-index period; and have prior BCG exposure. Those excluded from the study were patients with evidence of radical cystectomy and with muscle invasive or metastatic disease during the pre-index period. The index date was defined as the first administration of pembrolizumab treatment.

Pembrolizumab-treated patient demographics

Of the 126 patients included in the real-world setting, median age was 80 years (range, 51-90). The majority were male (77%), White (82%), and insured primarily through Medicare (92%). Further, 49% had a comorbidity score of 5 or more, with the most prevalent being renal disease (39%), diabetes without complications (37%), and chronic obstructive pulmonary disease (30%).

Of note, patients in the real-world setting were older, compared with the KEYNOTE-057 trial patients (median age, 80 vs 73, respectively), and many had multiple comorbidities.

All patients had received BCG, with a median of 10 instillations. In total, 44% of patients received adequate BCG therapy (defined as 5 or more induction instillations and 7 or more instillations within 9 months of the first instillation) prior to initiation of pembrolizumab monotherapy in the real-world setting.

In addition, 37% of patients received intravesical chemotherapy prior to pembrolizumab initiation (n = 187 administrations; median, 2.5), with the most commonly used being mitomycin (48%) and gemcitabine (31%).

The study authors acknowledged the study was limited by its data source and administrative claims data, as the identification of patients with bladder cancer was subject to incomplete and miscoded claims. Further, they added that the majority of patients included in this study were aged 65 years or older and insured primarily through Medicare, “so our findings may not be generalizable to younger individuals or those covered by other insurance plans.”

“Future studies are warranted to evaluate the clinical effectiveness of pembrolizumab in the real-world setting,” the study authors concluded.

Editor’s Note: This study was funded by Merck & Co, Inc.


1. Squire P, Sun Y, Dave H, Kapadia E, Turzhitsky V, Li H. Real-World Pembrolizumab Utilization Patterns for High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC): A Retrospective Claims-Based Analysis. Presented at: Society of Urologic Oncology (SUO) 23rd Annual Meeting; November 30-December 2; San Diego, California. Poster 86.

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