ASCO GU 2019: Perioperative Immunotherapy in Urothelial Carcinoma: State of Existing Evidence
Dr. Necchi pointed out that in MIBC there are few ongoing trials for IO neoadjuvant treatment such as PURE-01, ABACUS, and IO with or without chemotherapy. He summarized the PURE-01 study which showed that neoadjuvant pembrolizumab resulted in 42% of patients with pT0 and was safely administered in patients with MIBC. This study indicated that pembrolizumab could be a useful neoadjuvant therapy for the treatment of MIBC when limited to patients with PD-L1–positive or high-TMB tumors. He also summarized the ABACUS trial which showed that neoadjuvant atezolizumab is safe and associated with a significant pathological CR rate (29%). He then showed the data presented at ESMO 2018, using neoadjuvant gemcitabine with pembrolizumab in locally advanced UC has manageable toxicity, a comparable time to surgery as NAC, and is associated with robust disease downstaging (61%). He also highlighted the post-operative complications were comparable between the ABACUS and PURE-01 study, and this data will be presented at EAU 2019 next month. He also summarized the other ongoing neoadjuvant immunotherapy trials in MIBC.
Dr. Necchi then talked about the importance of biomarker discovery or genomic biomarkers that can predict response to NAC or immunotherapy and highlighted some of the published studies in this area. Tumor mutational burden (TMB) has emerged as the most reliable biomarker and using clinical T stage, TMB and PD-L1 expression status on a nomogram can predict pT0 response with significant accuracy. He also highlighted other possible biomarkers that can predict response and survival after neoadjuvant IO, and there is a clear need for additional biomarker research in this area.
He then concluded his talk by giving rational development of neoadjuvant IO agents in MIBC and stressed on opportunities for research and collaboration in this area. If patients have high PD-L1 and high TMB-they can either get single-agent IO or NAC if they are cis-platin eligible. Cisplatin ineligible patients can get single-agent IO. If patients have high PD-L1 or high TMB, and they are cisplatin eligible, they can get NAC and IO drugs or just NAC. Cisplatin ineligible patients can get single-agent-IO or combination IO. If PDL1 and TMB are both low, cisplatin eligible patients can get NAC. Cisplatin ineligible patients can go for straight cystectomy. In summary, pathologic response rates observed in single-agent IO studies are promising but there is a need to confirm association with long term improved outcomes. Chemotherapy plus IO combinations, and chemoradiation plus checkpoint blockage for bladder preservation is poised to make a significant impact in the management of localized muscle-invasive disease. Both strategies will require biomarker use for patient selection. Adjuvant IO trial results are pending, yet comprehensive approaches are being pursued and it will be fascinating to see the upcoming developments in this area.
Presented by: Andrea Necchi, MD, Fondazione IRCCS Istituto Nazionale dei Tumori
Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA. Twitter: @shekabhishek at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA