Long-term survival data from the first prospective, randomized biomarker validation trial in patients with muscle-invasive bladder cancer treated with cisplatin-based chemotherapy before surgery will be reported at the American Society of Oncology Genitourinary Cancers Symposium Clinic (GU ASCO) 2022) on February 18, 2022.
The results are from the S1314 clinical trial conducted by the SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).
Primary results from the S1314 study were published in the journal Clinical Cancer Research in 2021 and reported an association between a gene expression biomarker called the COXEN GC score and a tumor’s pathological response to chemotherapy.
The new findings presented at GU ASCO are the results of a prespecified secondary analysis of S1314 data that looked for associations between the COXEN score and how long a patient lived after starting treatment (a measure known as overall survival, or OS), and between the COXEN score and how long a patient lived without their disease getting worse (known as progression-free survival, or PFS).
The work was led by Thomas W. Flaig, MD, SWOG investigator at the University of Colorado Cancer Center and vice chancellor for research at the University of Colorado Anschutz Medical Center. "The work on S1314 was a tremendous collaborative effort between many institutions," Flaig said, "and provides important information about patients being treated with preoperative chemotherapy for bladder cancer."
The S1314 trial enrolled 237 patients with muscle-invasive urothelial bladder cancer that had not spread to other parts of the body (had not metastasized), all of whom were scheduled to undergo surgery for their cancer.
After enrolling in the study, patients were randomly assigned to receive neoadjuvant chemotherapy, that is, chemotherapy before surgery, in one of two treatment arms. Patients in the first group were treated with a combination of two drugs: gemcitabine and cisplatin (GC).
Those in the second arm were treated with a dose-dense cocktail of four drugs: methotrexate, vinblastine, doxorubicin and cisplatin (known as MVAC). All patients underwent surgery after completing chemotherapy . Doctors examined tumors removed from patients to determine whether they had shrunk in response to chemotherapy.
The COXEN score (short for co-expression extrapolation score) is generated by a test that measures the expression, or level of activity, of a specific set of genes in a patient’s tumor cells. The COXEN test is adapted to each treatment. Broadly speaking, it attempts to predict how sensitive a tumor is to a specific drug or combination of drugs.
The S1314 trial used a separate, treatment-specific COXEN test for each of the two treatment combinations. These two tests were called COXEN GC and COXEN MVAC.
Before the trial began, the researchers identified a specific cutoff score for each test: scores above that cutoff were considered favorable, scores below that cutoff were considered unfavorable.
The trial was designed to determine whether a better COXEN score was associated with a more favorable response to chemotherapy. The goal was to determine if the COXEN score could serve as a potential biomarker that could then be further validated in a prospective clinical trial.
Results from the primary trial had shown that the COXEN GC score could predict pathological response to chemotherapy among a pooled analysis of patients from the GC and MVAC treatment arms.
In the secondary analysis reported in GU ASCO, the researchers found no significant association between COXEN GC score and OS or PFS in the GC treatment group, nor between COXEN MVAC score and OS or PFS in the MVAC treatment group. However, when they looked at the COXEN GC score values for both treatment groups combined, they found that the score was a significant predictor of overall survival.
Flaig emphasized that there was much more to learn from S1314. "There is very little prospective data in this setting," she said, "and beyond the COXEN analysis reported here, patient samples and results from S1314 are being used to facilitate evaluation of several additional biomarkers."
The S1314 study was sponsored by NCI, led by SWOG, and conducted by the NIH-funded National Clinical Trials Network (NCTN). The study was funded by NIH/NCI through grants CA180888, CA180819, CA180820, and CA180821.
