ASCO GU 2017: Optimizing Outcomes in Muscle-Invasive and Metastatic Bladder Cancer - Session Highlights
Orlando, Florida USA (UroToday.com) Elizabeth Plimack, Fox Chase Cancer Center, discussed the molecular predictors of response to neoadjuvant chemotherapy. Predictive biomarker in indicative of outcome or invention or prognostic based on history. Reproducible, validated, accessible and significant (statistically). From the IMVigor trial PDL1 testing losing ability to discriminate among urothelial cancer patients. These findings were noted in KEYNOTE study as well highlighting the importance of validation in biomarker assessment. The neoadjuvant platform is optimal for predictive biomarker discovery. In the ddMVAC trial at Fox Chase, they noted gene alterations in the tissue samples extracted from that study and ATM1, RB1 and FANCC predicted pathologic response. Defects in these alterations were externally validated. Furthermore, these mutations correlated with improved survival response and survival in both the discovery and validation data sets. ERCC2 was further assessed and noted mutations enriched in responders in the discovery cohort and further validated with improved response and survival. The higher number of genomic alterations correlated with greater probability of response to cisplatin based chemotherapy.
Key defects in DNA repair genes confer sensitivity to cisplatin chemotherapy. P53-like subtypes at baseline predicts cisplatin resistance which was noted in discovery and validation cohorts. In addition to these validated biomarkers, COXEN and curated gene panel are of interest moving forward. The COXEN trial is assessing stand to dose dense cisplatin chemotherapy but also of upmost importance are the tissue to be obtained from this trial for future study of biomarkers. There is a Phase II trial of definitive chemotherapy in patients with deleterious DNA repair genes in order to determine response to treatments. The optimal gene signature in DNA repair genes should be defined in a larger dataset. Higher mutational load correlates with response to cisplatin and atezolizumab with further studies underway. In summary, discovery and validation are of upmost importance when assessing biomarkers.
Presenter: Elizabeth Plimack, Fox Chase Cancer Center
Contributed by Stephen B. Williams, MD, Assistant Professor, Division of Urology, The University of Texas Medical Branch at Galveston, Galveston, TX and Ashish M. Kamat, MD, Professor, Department of Urology, The University of Texas MD Anderson, Houston, TX