Given these new results, the algorithm for first line systemic treatment for metastatic urothelial cancers has changed in the cisplatin-ineligible patients: immune therapy or gemcitabine/carboplatin for PD-L1 positive patients and gemcitabine/carboplatin for PD-L1 negative patients. Multiple first line phase III trials of anti-PD-1/PD-L1 antibodies as monotherapy or in combination are underway in urothelial cancer and we actively await their results as they will likely have practice changing guidelines as well (ie IMvigor130, DANUBE, KEYNOTE-361, CheckMate-901). DANUBE is a randomized phase III trial of durvalumab with or without tremelimumab versus chemotherapy as 1st line treatment for metastatic urothelial cancer.
Dr. Powles also discussed treatment in the neoadjuvant space in organ-confined disease. Neoadjuvant atezolizumab has demonstrated response for operable urothelial cancers, primary in patients PD-L1 positive. Furthermore, in the PURE-01 study, PD-L1 positivity with RB1 genomic alteration may be biomarkers for pathologic response with neoadjuvant pembrolizumab. Niagra, randomizing patients to neoadjuvant gemcitabine and cisplatin or gemcitabine and cisplatin with durvalumab (with 12 months durvalumab therapy), is currently ongoing and has the potential for promising results. An update on KEYNOTE-057, a phase II trial of pembrolizumab for patients with high risk non-muscle invasive bladder cancer unresponsive to BCG, has demonstrated a 40% complete response at 3 months, with no patients reported having progressed to T2 disease. Lastly, erdafitinib is being studied, which may show promise for the future in treating selected patients with urothelial cancers as an antibody-drug conjugate.
In summary, the real world atezolizumab data is encouraging. Immune therapy in the front line cisplatin ineligible population is restricted to PD-L1 positive patients. Atezolizumab and pembrolizumab have impressive activity early in the disease with new targets holding promise for future treatments and investigations.
Presented by: Professor Thomas Powles, MBBS, MRCP, MD Centre, Experimental Cancer Medicine Professor of Genitourinary Oncology, Lead for Solid Tumour Research at Barts Cancer Institute, Director of Barts Cancer Centre
Written by: David B. Cahn, DO, MBS@dbcahn Fox Chase Cancer Center at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.