(UroToday.com) The 2022 GU ASCO Annual meeting included a urothelial carcinoma session featuring work from Dr. Thomas Flaig and colleagues presented results from SWOG S1314, a randomized phase II study of co-expression extrapolation (COXEN) with neoadjuvant chemotherapy for localized, muscle-invasive bladder cancer (MIBC) with overall survival follow up. This trial evaluated COXEN, a gene expression model, as a predictive biomarker in muscle-invasive bladder cancer patients randomized to Gemcitabine-Cisplatin or dose-dense Methotrexate-Vinblastine-Adriamycin/doxorubicin-Cisplatin (ddMVAC). Primary results correlating COXEN with pathologic response at surgery have been reported. This secondary analysis includes progression-free (PFS) and overall survival (OS).
Eligibility included Stage cT2-T4a N0 M0, urothelial bladder cancer (mixed histology allowed), ≥ 5 mm of viable tumor, cisplatin eligible, with plan for cystectomy. There were 237 patients randomized between ddMVAC, given every 14 days for 4 cycles, and gemcitabine-cisplatin, given every 21 days for 4 cycles. Cox regression was used to evaluate COXEN score or treatment arm association with PFS and OS, adjusting for stratification factors (stage and PS).
There were 167 patients included in the primary COXEN analysis all having either at least 3 cycles of chemo and surgery within 100 days of last chemo or having progressed while receiving chemo. The COXEN scores were not significantly prognostic for OS or PFS in their respective arms; the COXEN gemcitabine-cisplatin score was a significant predictor for OS in pooled arms. OS and PFS data for both scores are summarized as follows:
In the intent to treat analysis (n=227), there was no significant difference in OS or PFS for ddMVAC versus gemcitabine-cisplatin (for OS, HR 0.87, 95% CI 0.54-1.40, p = 0.57; for PFS HR 0.76, 95% CI 0.58-1.01, p = 0.055). The association of pathologic response with OS suggests that patients with no response have significantly worse survival than those with pT0/<=pT2 disease:
Dr. Flaig concluded his presentation of SWOG S1314 with the following take-home messages:
- The COXEN score may be prognostic of survival in those receiving platinum-based neoadjuvant treatment
- The randomized, prospective design provides estimates of OS and PFS for gemcitabine-cisplatin and ddMVAC that appear comparable, but this phase II trial is underpowered for definitive comparisons
- The prospective data and correlative samples from S1314 will allow for further assessment of COXEN and other RNA and DNA based predictive and prognostic biomarkers
Clinical trial information: NCT02177695.
Presented by: Thomas W. Flaig, MD, University of Colorado Anschutz Medical Campus, Aurora, COCo-Authors: Catherine Tangen, Siamak Daneshmand, Ajjai Shivaram Alva, M. Scott Lucia, David McConkey, Dan Theodorescu, Amir Goldkorn, Matthew I. Milowsky, Rick Bangs, Gary R. MacVicar, Bruno R. Bastos, Jared Fowles, Daniel Gustafson, Melissa Plets, Ian Murchie Thompson, Seth P. Lerner
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