(UroToday.com) The 2022 GU ASCO Annual meeting included a urothelial carcinoma session featuring work from Dr. Shilpa Gupta and colleagues presented results from BLASST-1, specifically biomarker analysis and updated clinical follow-up among MIBC patients receiving nivolumab, gemcitabine, and cisplatin. The BLASST-1 study is multi-center phase II trial evaluating the combination of nivolumab with gemcitabine-cisplatin as neoadjuvant therapy for patients with MIBC undergoing radical cystectomy (RC). The primary endpoint was pathologic downstaging (≤pT1N0). Safety, Relapse-free survival (RFS), Progression-free survival (PFS) and biomarker analyses were secondary endpoints. At GU ASCO 2020, the investigators previously reported a pathologic downstaging rate of 65.8% and pathologic complete response (pCR) rate of 49%. There were no safety concerns or delays to surgery. At GU ASCO 2022, Dr. Gupta correlates pathologic downstaging with biomarkers (Tumor mutational burden (TMB), PD-L1, and molecular subtypes) and provides updated clinical follow-up data.
Forty-one patients with MIBC (cT2-T4a, N≤1, M0) and candidates for RC were enrolled between February 2018 and June 2019. There were 90% of patients that were cT2N0, 7% that were cT3N0, and 3% cT4N1. Patients received cisplatin (70mg/m2) IV on D1, gemcitabine (1000mg/m2) on D1, D8 and nivolumab (360 mg) IV on D8 every 21 days for 4 cycles followed by RC within 8 weeks. The treatment schema for BLASST-1 is as follows:
For RNA-based analysis, GeneChip Human Exon 1.0 ST Array (Affymetrix) was used; baseline tumors from 37 patients passed quality control and had available transcriptome data. A cohort (n=223) of patients treated with neoadjuvant chemotherapy + RC was used as a comparator for molecular subtyping analysis. DNA was extracted from baseline pre-treatment tumor samples and sequenced to an average depth of 150X and the DNA extracted from matched normal tissue (peripheral blood) to a mean depth of 50X. PD-L1 expression was assessed using IHC 28-8 antibody on baseline tumors.
At a median follow-up of 15.8 months,12-month RFS rate was 85.4% and PFS including death from any cause was 83%. There were no long-term safety concerns. Molecular subtyping found patients with a basal-type tumor (Basal or Claudin-low) had a more favorable overall pathologic downstaging (73%), with pathologic downstaging in 9/13 in basal (69%) and 4/5 in claudin-low (80%) compared to overall pathologic downstaging of 58% for the luminal-type tumors (Luminal or Infiltrated luminal). For luminal-types tumors, pathologic downstaging was seen in 63% of these tumors, with 6/11 (54%) in infiltrated luminal. In contrast, in the comparator neoadjuvant chemotherapy cohort, the pathologic downstaging rates were similar for basal-type and luminal-type tumors, with 44% and 48%, respectively. As follows is a summary of pathologic response by molecular subtype:
There was no correlation of pathologic downstaging with TMB or PD-L1 expression from bassline pre-treatment tumors. Biomarker analyses from residual tumors in RC tissues are ongoing.
Dr. Gupta concluded her presentation of BLASST-1 with the following concluding statements:
- The combination of nivolumab + gemcitabine-cisplatin was safe and efficacious in MIBC with encouraging outcomes of pathologic downstaging and relapse-free survival at a median follow-up of 15.8 months
- Molecular subtyping results suggest basal-type tumors may respond more favorably to this chemo-immunotherapy treatment regimen.
Clinical trial information: NCT03294304.
Presented by: Shilpa Gupta, MD, Cleveland Clinic Taussig Cancer Institute, Cleveland, OHCo-Authors: Ewan Gibb, Guru P. Sonpavde, Sumati Gupta, Benjamin L. Maughan, Neeraj Agarwal, Bradley Alexander McGregor, Christopher Weight, Xiao X. Wei, David Johnson Einstein, Christopher B. Dechet, Mark A. Preston, Matthew Mossanen, Bharat Thygarajan, Markus Eckstein, C. Marcela Diaz-Montero, Paari J. Murugan, Peter C. Black, Badrinath R. Konety
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 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022