(UroToday.com) The 2022 Society of Urologic Oncology (SUO) annual meeting featured a session on bladder cancer, including a presentation by Dr. Patrick Squires discussing real-world pembrolizumab utilization patterns for high-risk non-muscle invasive bladder cancer. The typical treatment for high-risk non-muscle-invasive bladder cancer is transurethral resection of the bladder tumor with subsequent intravesical instillations of Bacillus Calmette-Guerin (BCG) immunotherapy. Although initial responses to BCG are high, up to 50% of patients have recurrence or become BCG-unresponsive. Pembrolizumab was approved by the US Food and Drug Administration in January 2020 based on the results of the KEYNOTE-057 study for the treatment of patients with BCG-unresponsive, NMIBC with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.1
However, little is known about real-world utilization of pembrolizumab in patients with high-risk non-muscle-invasive bladder cancer. The present study aimed to describe patient demographic and clinical characteristics, real-world time on treatment, real-world time to next treatment, real-world treatment free interval, and on-treatment rates in high-risk non-muscle-invasive bladder cancer patients initiating pembrolizumab within the Optum Research Database.
Eligible patients for this retrospective cohort study included those aged ≥18 years with bladder cancer diagnosis codes who initiated pembrolizumab between January 1, 2020 and December 31, 2021 (index date defined as the first pembrolizumab administration), had continuous enrollment during the 6-month pre-index period, and prior BCG exposure. Adequate BCG therapy was defined as ≥5 induction instillations and a total of ≥7 instillations within 9-months of the first instillation. Patients were followed until the end of database availability (March 31, 2022), end of enrollment or death, whichever occurred first. Patients with evidence of radical cystectomy, muscle-invasive or metastatic-disease pre-index were excluded. Primary outcomes included pembrolizumab real-world time on treatment, real-world time to next treatment, real-world treatment free interval, and on-treatment rates at 3, 9, and 18-months. Secondary outcomes were demographics, clinical characteristics, and treatment patterns prior to and after pembrolizumab initiation.
This study identified 126 patients who initiated pembrolizumab for high-risk non-muscle-invasive bladder cancer (median age 80 years, 96.3% ≥65 years; 77% male; 82% white; 92% insured primarily through Medicare; 49% had 5+ Quan-Charleston comorbidities) with a median follow-up of 10.6 (range: 0.8-26.3) months. Prior to initiating pembrolizumab, the median number of BCG instillations was 10 (IQR 6-14) and 44% demonstrated adequate BCG therapy. Median time from last BCG until the index date was 4.8 months (IQR 3.3-9.2). Median pembrolizumab real-world time on treatment was 6.8 months (95% CI 5.7-9.0):
Pembrolizumab on-treatment rates were 78% (95% CI 71%-86%), 39% (95% CI 31%-50%), and 19% (95% CI 12%-30%) at 3, 9, and 18 months, respectively:
During follow-up, 30% of patients received subsequent therapies after pembrolizumab initiation: 9 patients underwent radical cystectomy with a median time from initiation of pembrolizumab to radical cystectomy of 9.2 months:
The median time to next treatment from pembrolizumab was 18.7 months and the median treatment free interval was 13.0 months.
Dr. Squires concluded his presentation discussing real-world pembrolizumab utilization patterns for high-risk non-muscle invasive bladder cancer with the following take home messages:
- Compared to those enrolled in KEYNOTE-057, patients in the present real-world study were older (KEYNOTE-057: median age 73 [IQR 63-79]; 70% ≥65 years)
- The median pembrolizumab real-world time on treatment was similar in duration to the clinical trial setting (6.8 versus 4.2 months in KEYNOTE-057)
- Almost half (44%) of the present cohort achieved adequate BCG therapy, thereby demonstrating modest heterogeneity of initial BCG treatments prior to beginning pembrolizumab
- In KEYNOTE-057, 41% of patients demonstrated complete response at 3-months and continued pembrolizumab therapy
- Although response rates and reasons for discontinuation are unavailable in claims data, 78% of real-world patients remained on pembrolizumab at month 3 and 39% at month 9
- Longer follow-up may be required to contextualize real-world treatment patterns by further allowing for natural disease progression and use of additional treatments
- Future studies are warranted to evaluate the clinical effectiveness of pembrolizumab in the real-world setting including complete response, durability, and progression rates
Presented by: Patrick Squires, PharmD, PhD, Merck & Co., Inc., Rahway, NJ
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 23rd Annual Meeting of the Society of Urologic Oncology (SUO), Nov 30 – Dec 2, 2022. San Diego, CA
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