SUO 2018: Phase 2 Study of Pembrolizumab Monotherapy for High-Risk, Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Bacillus Calmette-Guerin (BCG): Results from Keynote-057

Phoenix, Arizona ( Previous studies have demonstrated that constitutive PD-1 activation has been implicated in BCG resistance. While radical cystectomy is a standard option for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC), it is associated with a high rate of perioperative morbidity and has a significant impact on patient quality of life.

In patients with metastatic urothelial carcinomas, pembrolizumab has been demonstrated to have activity in the metastatic space. As part of the Oral Abstract session at the 2018 annual meeting of the Society of Urologic Oncology, Dr. Arjun Balar discussed the results of the Keynote 057 study. This is a single arm phase 2 study of efficacy and safety of pembrolizumab monotherapy in patients with high risk, BCG-unresponsive NMIBC. In this abstract, Dr. Balar presented the results for patients with carcinoma-in-situ or carcinoma-in-situ plus papillary tumors. This was an interim efficacy and safety analysis.

In this clinical trial, patients were given pembolizumab 200mg Q3 weeks for 24 months or until recurrence, progression, or toxicity. This cohort included patients with histologically confirmed high-grade BCG unresponsive non-muscle invasive bladder cancers, including CIS alone or CIS with papillary cancers. These patients must have been treated with adequate BCG therapies, defined as 5/6 induction BCG instillations and 2/3 maintenance therapy instillations and refused or unable to undergo radical cystectomy. Endpoints evaluated included complete response rates, disease-free survival, safety, and duration of response.

Analysis included 101 patients enrolled with a median follow up of 9.4 months. Median age was 73 years. Staging included approximately: 72% CIS, 15% CIS + HGTa, and 13% CIS + HGT1. At 3 months, 36.5% had complete response. Of the patients with a complete response, median duration was 8.1 months. 55.7% of patients had treatment-related adverse effects with Grade 3-5 in 11.3% of patients. 3.1% of patients had to discontinue treatment due to these adverse effects and 1 death was treatment-related.

Dr. Balar concluded that in this study, pembrolizumab demonstrated encouraging antitumor activity, with a compelling complete response rate and an adequate duration of response in patients with BCG-unresponsive CIS. None of the patients who recurred while on trial progressed to muscle-invasive disease. He feels that the safety/tolerability profile of this drug is appropriate and is consistent with prior trials utilizing this medication. He concluded his talk by highlighting the KEYNOTE-676 trial, which will be a phase III trial studying pembrolizumab in combination with BCG in patients with high-risk NMIBC that is persistent or recurrent following induction BCG immunotherapy. This trial will begin accruing patients soon and data should be available within the next few years.

Presented By: Arjun V. Balar, MD, PhD, NYU Langone Medical Center

Written by: David B. Cahn, DO, MBS, Fox Chase Cancer Center, Philadelphia, PA, @dbcahn, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona