(UroToday.com) The 2024 American Society for Radiation Oncology (ASTRO) annual meeting held in Washington D.C., between September 29 and October 2 was host to the session EDU 16 - Management of Unfavorable Intermediate-Risk Prostate Cancer: Role of SBRT, Brachytherapy and Androgen Deprivation Therapy. Dr. Shang-Bin Qin presented their investigator-initiated study using Pembrolizumab Monotherapy Following Tri-Modality Treatment for Selected Patients with Muscle-Invasive Bladder Cancer.
Over the past few decades, there has been a growing trend toward using organ-preserving therapies in the management of bladder cancer, with trimodal therapy (TMT) emerging as an established multi-disciplinary approach that provides outcomes comparable to radical cystectomy (RC). However, the challenges of TMT are evident, with reported 5-year local recurrence rates nearing 40% and 5-year distant metastasis rates exceeding 30% according to Dr Qin.
Dr Qin and colleagues in a pilot incorporating a stereotactic ablative body radiotherapy (SABR) boost into the TMT regimen found that this regimen was well-tolerated and effective for patients with muscle-invasive bladder cancer (MIBC). Therefore, they decided to conduct this study to evaluate the effectiveness of Pembrolizumab as maintenance therapy following TMT with SABR boost in MIBC patients hypothesizing that Pembrolizumab maintenance therapy can improve PFS for patients who received TMT and achieved a complete response after TMT.
This was an investigator-initiated Phase 2, single-arm, single-site trial evaluating Pembrolizumab as maintenance therapy in patients with muscle-invasive bladder cancer (MIBC) who had undergone TMT and achieved a complete response (CR). The definition of CR included the absence of disease as determined by bladder MRI and cystoscopy. The primary endpoint of the study was progression-free survival (PFS), while secondary endpoints included overall survival (OS), bladder-intact event-free survival (BI-EFS), and safety signals. The study design is shown below:
In this study, participants underwent maximal transurethral resection of bladder tumor (TURBT) followed by SABR at a dose of 18 Gy in 3 fractions, delivered to the tumor or tumor bed within the filling bladder. Concurrently, patients received conventionally fractionated radiotherapy (CFRT) to the pelvic lymph nodes and empty bladder, totaling 45 Gy in 25 fractions, along with weekly Gemcitabine. Following treatment, patients underwent cystoscopy and MRI evaluation. Those who achieved a complete response (CR) were offered Pembrolizumab maintenance therapy for one year, while patients who did not achieve a CR proceeded to salvage radical cystectomy. The trial treatment schema is illustrated below.
At the cutoff date of March 2024, a total of 46 participants were accrued for the study. Among these participants, 78% were male, and 85% had a clinical stage of T2. More than 60% of the participants underwent incomplete TURBT, and 96% received concurrent chemotherapy, while 20% had received neoadjuvant chemotherapy. The baseline characteristics are shown in the table below.
At the time of the data cutoff, the median follow-up was 10 months, during which a total of ten participants completed Pembrolizumab for 17 cycles. The estimated 1-year progression-free survival (PFS), local control, and overall survival (OS) rates were 85%, 93%, and 97%, respectively.
Of the 46 patients treated, 42 were progression-free, with 2 developing distant metastases and one death due to COVID-19. Among the 42 patients who were progression-free, 40 maintained an intact bladder and continued to be free of progression at the time of analysis, while 2 experienced bladder recurrences—one was treated with TURBT and the other with RC.
After a median follow-up time of 10 months, 10 patients completed Pembrolizumab for 17 cycles. Immune-related adverse events (AEs) occurred in 11 patients (24%), with Grade 3 treatment-related AEs observed in 3 patients (7%). A total of 17 patients discontinued Pembrolizumab due to treatment-related AEs, with a complete breakdown of safety events shown in the table below. Notably, none of the patients reported Grade ≥ 3 late GU or GI toxicity.
Dr. Qin concluded his presentation with the following remarks:
- Pembrolizumab maintenance therapy after TMT with SABR boost to bladder tumor was well tolerated with promising efficacy in the early analysis (median follow-up 10 months)
- Immune-related toxicity was consistent with findings from prior Pembrolizumab monotherapy trials.
- Ongoing analyses of banked blood and tissue specimens will be presented in future reports.
Presented by: Shang-Bin Qin, MD, Department of Radiation Oncology, Prostate Cancer Radiotherapy Center, Peking University First Hospital, Beijing, China.
Written by: Julian Chavarriaga, MD – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @chavarriagaj on Twitter during the 2024 American Society for Radiation Oncology (ASTRO) annual meeting held in Washington D.C., between the 29th of September and the 2nd of October.