Updated interim results of phase 2 trial of pembrolizumab for 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 tumours.

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 enrolment (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" (see Table).

1. D'Elia C, et al. Urol Int 2017;98(3):255-261.

Posted on 21 May, 201917 March, 2021