SUO 2018: The Case for Neoadjuvant Immunotherapy

Phoenix, Arizona (  Dr. Necchi started his talk by pointing out that cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care (SoC) for muscle-invasive bladder cancer (MIBC) but the adherence to SoC is poor, and there are no good predictive biomarkers. Therefore, there is a need for other agents possibly immuno-oncology (IO) drugs. He highlighted the study by Forde et al. in NEJM in lung cancer patients, where neoadjuvant nivolumab was used and was associated with few side effects, did not delay surgery, and induced a significant pathological response in 45% of resected tumors.

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 study which showed that neoadjuvant pembrolizumab resulted in 42% of patients with pT0 and was safely administered in patients with MIBC. This study indicates 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 highlighted one of the posters presented at SUO 2018 meeting, looking at the role of bladder multiparametric magnetic resonance imaging (mpMRI) to predict pathologic response to neoadjuvant pembrolizumab. This study showed that radiologic response was obtained in 14 patients (41.2%). Median “mean ADC” of post-therapy lesions in pT0 patients was 1 versus 0.8 in non-pT0 patients. In total, 8 patients (23.5%) showed CR (n=7) or PR (n=1), and 7 patients (20.6%) showed ADC≥1, respectively. 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 other ongoing neoadjuvant 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. He then concluded his talk by giving rational development of neoadjuvant IO agents in MIBC and stressed on opportunities for research 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 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. If PDL1 and TMB are both low, cisplatin eligible patients can get NAC. Cisplatin ineligible patients can go for straight cystectomy.

Presented by: Andrea Necchi, MD, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy

Written by: Abhishek Srivastava, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, Pennsylvania, @shekabhishek, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona