Co-primary endpoint analysis of HCRN GU 16-257: Phase 2 trial of gemcitabine, cisplatin, plus nivolumab with selective bladder sparing in patients with muscle-invasive bladder cancer (MIBC).

Authors

null

Matt D. Galsky

The Tisch Cancer Institute, Mount Sinai, New York, NY

Matt D. Galsky , Siamak Daneshmand , Sara C Lewis , Kevin G. Chan , Tanya B. Dorff , Jeremy Paul Cetnar , Ronac Mamtani , Christos Kyriakopoulos , Mahalya Gogerly-Moragoda , Sudeh Izadmehr , Menggang Yu , Qianqian Zhao , Tomi Jun , Reza Mehrazin , John P. Sfakianos , Sumanta Monty Pal

Organizations

The Tisch Cancer Institute, Mount Sinai, New York, NY, USC Institute of Urology, USC/Norris Comprehensive Cancer Center, Los Angeles, CA, Icahn School of Medicine at Mount Sinai, New York, NY, City of Hope, Duarte, CA, Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, Oregon Health & Science University, Portland, OR, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, University of Wisconsin-Madison Carbone Cancer Center, Madison, WI, Icahn School of Medicine at Mount Sinai, New York, University of Wisconsin, Madison, WI, University of Wisconsin Madison, Madison, WI, Sema4, Stamford, CT, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, NY, City of Hope Comprehensive Cancer Center, Duarte, CA

Research Funding

Pharmaceutical/Biotech Company
BMS, V Foundation

Background: Transurethral resection of bladder tumor (TURBT) plus systemic therapy has been known for decades to achieve durable bladder-intact survival in a subset of patients with MIBC but efforts to advance this paradigm have been complicated by a lack of (a) prospective studies, (b) rigorous approaches to assess and define clinical complete response (cCR), and (c) integration of novel therapies. Methods: Eligible patients were cisplatin-eligible with cT2-T4aN0M0 urothelial bladder cancer. Patients received 4 cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging including urine cytology, MRI/CT of the bladder, cystoscopy and bladder biopsies. Patients achieving a cCR (normal cytology, imaging, and cT0/Ta) were eligible to proceed without cystectomy and receive nivolumab q2 weeks x 8 followed by surveillance. Patients not achieving cCR were recommended to undergo cystectomy. Coprimary endpoints included (1) cCR rate and (2) association between cCR and 2-year outcomes. The key secondary endpoint was the impact of pre-specified baseline genomic alterations on outcomes. Additional biomarkers to refine patient selection were also explored. Results: Between 8/2018-11/2020, 76 patients were enrolled at 7 sites (male 79%, median age 69; cT2 = 56%, cT3 = 32%, cT4 = 12%). Median follow-up is 27 months. 72/76 patients underwent clinical restaging and a cCR was achieved in 33/76 (43%; 95% CI: 32%, 55%). One cCR patient opted for immediate cystectomy (ypTaN0M0). Outcomes are summarized in the Table. Baseline ERCC2, ATM, FANCC, or RB1 alterations were not, but tumor mutational burden ≥ 10 mutations/mb was, significantly associated with the composite endpoint of ypT0 (immediate cystectomy) or 2-year bladder-intact metastasis-free survival (BIMFS). On landmark analysis, VI-RADS (Vesical Imaging–Reporting and Data System) score (3-5 versus 1-2) on restaging MRI (central blinded review) was associated with inferior BIMFS (HR 4.5; p = <0.01) and MFS (HR 19.3; p <0.01). Circulating tumor DNA data will be presented at the meeting. Conclusions: TURBT followed by gemcitabine, cisplatin, plus nivolumab achieves stringently defined cCR in a substantial subset of patients with MIBC. ≥2-year bladder-intact survival is achieved in the majority of patients with a cCR. Clinical trial information: NCT03558087.

% at 2 yearsGroupEstimate95% CI
AlivecCR100%NA
No cCR75.8%58.1%, 86.8%
Alive, metastasis freecCR96.6%78.0%, 99.6%
No cCR74.6%57.9%, 85.5%
Alive, bladder intactcCR72.2%53.2%, 84.5%

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Abstract Details

Meeting

2023 ASCO Genitourinary Cancers Symposium

Session Type

Rapid Oral Abstract Session

Session Title

Rapid Abstract Session: Urothelial Carcinoma

Track

Urothelial Carcinoma

Sub Track

Therapeutics

Clinical Trial Registration Number

NCT03558087

Citation

J Clin Oncol 41, 2023 (suppl 6; abstr 447)

DOI

10.1200/JCO.2023.41.6_suppl.447

Abstract #

447

Abstract Disclosures