2021 ASCO Locally advanced MIBC: When will dual immunity + radiotherapy replace cystectomy?

The 2021 American Society of Clinical Oncology (ASCO) Annual Meeting will be held online from June 4th to 8th.
As one of the largest and most popular events in oncology, the ASCO Annual Meeting will showcase the latest cutting-edge developments to scholars from all walks of life
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The IMMUNOPRESERVE-SOGUG study explored the results of dual immunotherapy + simultaneous radiotherapy for locally advanced muscle invasive bladder cancer (MIBC)
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At this year's ASCO conference, the study announced preliminary results
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Background: Bladder sparing combination therapy is an alternative to radical cystectomy for selected patients with myometrial invasive bladder cancer (MIBC)
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Preclinical studies have shown that the addition of dual immune checkpoint inhibitors to radiotherapy (RT) seems to activate other immune mechanisms and enhance anti-tumor activity
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This study aims to explore the safety and anti-tumor activity of the combined regimen in MIBC patients
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Methods: IMMUNOPRESERVE-SOGUG is a phase II study.
T2-4a N0 M0 stage locally advanced MIBC, ECOG 0~1, no contraindications to immunotherapy, intentional bladder retention or unsuitable for cystectomy were included in the study
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The patient first underwent transurethral tumor resection, followed by valizumab (1500 IV) + tremelimumab (75 mg IV) (Q4W, 3 doses)
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Routine radiotherapy was started after 2 weeks, with a small pelvic dose of 46 Gy and a bladder dose of 64-66 Gy.
For patients with residual or recurrent MIBC, rescue cystectomy was given
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The primary endpoint is the complete response (CR) rate in the ITT population (defined as no MIBC on tumor biopsy after treatment)
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The study adopted a two-stage design (CR rate P0=5, P1=0.
7, A=0.
10, b=0.
20).
The first 12 patients had at least 6 CRs to expand to the second 20-patient cohort
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Results: From January 2019 to August 2020, the study included 32 patients from 6 centers, with a median age of 71 years, 24 and 8 patients with ECOG PS of 0 and 1, respectively
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25 patients were male
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There were 28 cases, 3 cases, and 1 case, respectively, with clinical stages of T2, T3, and T4a
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All patients received at least 2 cycles of immunotherapy
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The median RT dose was 64 Gy (60-65), 81% (26 patients) achieved CR after treatment, 2 patients had residual disease, and 4 patients died of COVID 19 due to rejection, clinical reasons, and suspected death.
To treat related peritonitis, the efficacy cannot be evaluated
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At a median follow-up of 12.
7 months, 2 patients underwent salvage cystectomy due to MIBC and T1 recurrence, respectively
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The 12-month intact bladder disease-free survival rate (DFS), the 12-month DFS rate and the 12-month overall survival rate are expected to be 73%, 76%, and 87%, respectively
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A total of 31 patients (97%) had radiotherapy and/or immunotherapy-related adverse events, of which diarrhea (41%) and urinary system diseases (37%) were the most common
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Treatment-related grade 3 or 4 adverse events occurred in 31% of patients, the most common of which were gastrointestinal toxicity (12%), acute renal failure (6%) and hepatitis (6%)
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Conclusion: Duvalimab + tremelimumab + simultaneous RT is safe and feasible.
It shows good efficacy in most patients with bladder preservation and is well tolerated.
It is necessary to further explore whether this regimen can replace bladder cancer resection
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Clinical trial information: NCT03702179
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Reference: Phase II trial of durvalumab plus tremelimumab with concurrent radiotherapy (RT) in patients (pts) with localized muscle invasive bladder cancer (MIBC) treated with a selective bladder preservation approach: IMMUNOPRESERVE-SOGUG trial.
abstract 4505.
Oral Abstract Session