Highlights from

EAU 2019

European Association of Urology annual congress

Barcelona 15-19 March 2019

Updated interim results of Keynote-057: phase 2 trial of pembrolizumab for patients with high-risk NMIBC unresponsive to BCG

Updated results of KEYNOTE-057 among patients with non-muscle invasive bladder cancer (NMIBC) suggest that systemic immunotherapy with pembrolizumab (200 mg every 3 weeks) has encouraging activity in patients with high-risk, BCG-unresponsive CIS with or without papillary tumors.

Prof. Ashish Kamat (MD Anderson Cancer Center, Houston, USA) shared the interim update on immune checkpoint inhibitors which demonstrated efficacy in metastatic bladder cancer. The PD-1 inhibitor pembrolizumab was studied in BCG-unresponsive patients with CIS (+/- Ta or T1). Out of 103 patients, 31% had an impressive durable complete response, with no individuals progressing to MIBC or developing other metastases. These promising results have already led to the initiation of a phase 3 trial comparing the combination of systemic pembrolizumab plus intravesical BCG to re-introduction of BCG alone, currently open to enrollment (KEYNOTE-676).

The toxicity profiles for immunotherapy necessitate vigilance and timely intervention of any adverse events, since they can potentially be serious, and occasionally fatal if not treated. Radical cystectomy, the current standard of care after BCG failure, however, has a 2-5% post-operative mortality rate[1]. In comparison, finding the best agent or combination of agents, to treat these patients is the topic of many research studies.

Prof. Kamat: "The results of these impending trials will almost certainly be practice-changing especially as we are currently are facing a worldwide shortage of BCG".

IdentifierTrial
NCT02792192Phase 1b/2 Safety and Pharmacology study of atezolizumab alone and in combination with BCG in high risk NMIBC
NCT02451423Phase 2 study of atezolizumab in subjects with non-metastatic TC of the bladder
NCT02844816Phase 2 study of atezolizumab in recurrent BCG-unresponsive NMIBC
NCT03317158ADAPT-BLADDER: durvalumab monotherapy (cohort 1) and durvalumab +BCG (cohort 2s and ERBT (cohort 2b) in BCG-unresponsive NMIBC
NCT02901548Phase 2 durvalumab for BCG-refractory urothelial carcinoma in situ of the bladder
NCT03519256Checkmate 9UT: Phase 2 nivolumab or nivolumab + BMS986205 +/- in BCG-unresponsive NMIBC
NCT02625961KEYNOTE-057: Phase 2 study of pembrolizumab in BCG-refractory high-risk NMIBC
NCT03167151Phase 1/2 Marker Lesion Study assessing safety, tolerability and efficacy if pembrolizumab in intermediate-risk recurrent NMIBC
NCT03711032KEYNOTE-676: Phase 2 BCG +/- pembrolizumab in high-risk NMIBC that is persistent or recurrent following BCG induction.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.