LAUSR

org/10.1200/JCO.18.01148 (2018) Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy (RC) is the standard-of-care approach for patients with muscle-invasive bladder cancer (MIBC); however, this approach is rarely used owing to poor tolerability. Now, new data from the PURE-01 study demonstrate the potential of the anti-PD-1 antibody pembrolizumab as an alternative to chemotherapy in this setting. In a single-arm, window-of-opportunity trial, 50 patients with a confirmed diagnosis of MIBC requiring RC received three courses of pembrolizumab before surgery, with a prespecified primary end point of T0 disease on examination of the RC specimen. All patients underwent RC as planned and 21 patients (42%) had T0 disease. A further 6 patients had incomplete responses, resulting in 27 patients (68.2%) being downstaged to non-muscle-invasive disease. Four patients discontinued pembrolizumab owing to lack of response on MRI and subsequently received neoadjuvant chemotherapy, as permitted by the trial design. Three patients had a grade ≥3 adverse event, of which one resulted in treatment discontinuation. Thyroid dysfunctions were the most common adverse events of any grade, occurring in 18% of patients. The majority of patients in the cohort (35) had PD-L1-positive tumours before treatment (defined as PD-L1 expression on >10% of tumour or immune cells, also referred to as combined-positive score; CPS) and had better rates of downstaging to T0 (54.3%) than those with PD-L1-negative (CPS <10%) tumours (13.3%). Examinations of pretreatment tumour mutational burden (TMB) revealed a positive nonlinear correlation with T0 response, and the authors suggested a cut-off of 15 mutations per megabase as a predictor of clinical benefit. These findings suggest that pembrolizumab provides a more effective alternative to cispl atin in the neoadjuvant setting; data from longer-term follow-up monitoring are eagerly awaited.