At the recent Genitourinary Cancers Symposium, new data was presented by Dr. Sumanta Pal, Co-Director of the Kidney Cancer Program at the City of Hope Cancer Center, on behalf of lead investigator Jeffrey S. Ross, MD, Chairman of Pathology at Albany Medical College and Medical Director at Foundation Medicine, showing potential new therapy options for those with advanced urinary bladder cancer, revealed by comprehensive genomic profiling. When bladder cancer is in an advanced stage, it is difficult to treat, and the current standard of care using cytotoxic chemotherapy often proves insufficient, contributing to the morbidity and mortality associated with this disease. There were almost 75,000 new cases of bladder cancer diagnosed in 2014, and the associated five-year survival rate is only ~34% for regional disease and drops to ~6% once the cancer has spread, or metastasized.
In this study, 295 patients with advanced stage bladder cancer received comprehensive genomic profiling (FoundationOne®) in the course of clinical care. 93% of these patients were identified to have at least one clinically relevant genomic alteration driving their cancer – i.e. an alteration associated with a targeted therapy currently on the market or actively studied in clinical trials. Based on the results of the comprehensive genomic profiling, these patients had potential targeted therapeutic options opened to them that may be more effective and less toxic than existing standard-of-care chemotherapy options.
Among the alterations detected by comprehensive genomic profiling, there was a notably high frequency of ERBB2, or HER2, alterations that were not amplifications of the gene, which are most commonly detected by standard testing methods such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) and associated with anti-HER2 targeted treatment options. Patients with these non-amplification alterations are expected to respond similarly to anti-HER2 therapy, and the alterations would not have been detected by testing methods other than comprehensive genomic profiling.
Several patients treated based on the results of comprehensive genomic profiling showed promising responses to targeted therapies:
- A 60 year old female patient with advanced disease was found to harbor a NF2 deletion and showed disease regression over 13 months of therapy with everolimus and paclitaxel (case recently published in European Urology)
- A 67 year old female patient with relapsed disease was found to harbor a FGFR3 amplification, or copy number alteration, and showed a partial response to pazopanib, which has been maintained over 6 months (case recently published in European Urology)
- A 73 year old male patient with relapsed metastatic disease was found to harbor a FGFR1-NTM fusion, or rearrangement, and responded to pazopanib and everolimus.
These data contribute to the growing applications of comprehensive genomic profiling in identifying potential additional treatment options for patients with a wide range of cancer types. The high frequency of clinically relevant genomic alterations and the responses to targeted therapies observed in these patients with urinary bladder cancer demonstrate the applicability of detecting all classes of genomic alterations: single base pair substitutions, insertions and deletions, copy number alterations and rearrangements. Further exploration of the application of comprehensive genomic profiling of urinary bladder cancers may help to address many of the challenges of treating this disease.