AUA 2017: What is Best Systemic Therapy for Metastatic/Invasive Bladder Cancer?

Boston, MA ( Drs. Gopa Iyer and Arjun Balar debated the relative risk/benefit profiles of cisplatin-based neoadjuvant chemotherapy versus immunotherapy.

Dr. Iyer observed that cisplatin-based regimens are still the gold standard despite recent excitement about immunotherapy. Gemcitabine/cisplatin or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin are National Comprehensive Cancer Network category 1 recommendations for metastatic urothelial carcinoma. He stated that based on the survival curves from some trials, approximately 12% to 15% of metastatic cancer can be cured and also indicated that carboplatinum may be substituted in cisplatin-ineligible patients with overall response rates (ORRs) of 30% to 41% in select patients. However, in the second-line setting, the ORRs for this therapy drop to 10% to 20%.

For cisplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer, Dr. Iyer reminded the audience that level-1 evidence shows the benefit of this approach without worsening of surgical morbidity or delays. Southwest Oncology Group 8710 (Grossman et al.) showed improved 5-year survival of 57% versus 43% in the non-neoadjuvant chemotherapy arm. Pathologic response rate (pT0 at cystectomy) correlated strongly with long-term survival. Meta-analysis has shown 5% absolute overall survival benefit. New studies show that defective DNA damage responsive genes have exquisite cisplatin sensitivity and may be useful clinical markers for cisplatin recipients.

Dr. Balar referred to immunotherapy as “A new standard in bladder cancer.” The efficacy of immunotherapy in bladder cancer makes intuitive sense given its known high somatic mutational burden, likely tobacco-carcinogen-related, leading to high levels of neoantigens. He pointed out that in some series, 50% to 70% of patients are cisplatin-ineligible and 20% to 40% are never treated (presumably over fear of adverse effects [AEs]), uncovering a huge unmet need for better tolerated but still effective therapies. Generally, immunotherapy trials in bladder cancer have shown ORRs around 15% to 20%, with median overall survival of 7 to 8 months in second line. Finally, in terms of tolerability, these agents are being given in the trial setting to much older sicker patients, suggesting fewer AEs than with traditional chemotherapy. However, there are still 15% Grade 3 or higher AEs, and immune-related AEs can be severe and must be monitored.

Presented By: Gopa Iyer, MD, Memorial Sloan Kettering Cancer Center, and Arjun Balar, MD, NYU Perlmutter Cancer Center, New York, NY

Written By: Jed Ferguson, MD, PhD, and Ashish Kamat, MD. MD Anderson Cancer Center, Department of Urology, Houston, TX

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA

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