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Can Treatment-Specific COXEN Scores Predict Responses to Neoadjuvant Chemotherapy for Bladder Cancer?

By: Julia Fiederlein
Posted: Monday, May 3, 2021

Dose-dense MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) and gemcitabine plus cisplatin are commonly used to treat muscle-invasive bladder cancer. Ian M. Thompson, Jr, MD, of The University of Texas Health Science Center at San Antonio, and colleagues conducted a study to determine whether the scores from a dose-dense MVAC- or gemcitabine/cisplatin-specific co-expression extrapolation (COXEN) algorithm-generated gene expression model may be used as biomarkers in patients undergoing radical cystectomy. The results of the phase II SWOG S1314 trial were published in Clinical Cancer Research.  

“Treatment-specific COXEN scores were not significantly predictive for response to individual chemotherapy treatment,” the investigators commented. “The [gemcitabine/cisplatin-specific] COXEN gene expression model score was significantly associated with downstaging in the pooled arms. Additional biomarker development is planned.”

A total of 237 cisplatin-eligible patients with cT2–T4a N0 M0 urothelial bladder cancer who planned to undergo cystectomy were randomly assigned in a 1:1 ratio to receive dose-dense MVAC or gemcitabine plus cisplatin. Of this study population, 167 were evaluable for the primary COXEN GEM assessment; unevaluable patients were included in the intention-to-treat efficacy and safety analyses.

The odds ratio for complete pathologic response with the gemcitabine/cisplatin-specific score was 2.63 (P = .10); the odds ratio was 1.12 with the dose-dense MVAC-specific score (P = .82). When the gemcitabine/cisplatin-specific score was applied to both treatment arms for the outcome of downstaging, the odds ratio was 2.33 (P = .02). In the intention-to-treat population, the complete pathologic response rate was 28% with dose-dense MVAC and 30% with gemcitabine plus cisplatin (P = .75); the rates of downstaging were 47% and 40%, respectively (P = .27).

Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.



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