KEYNOTE-57 Findings Demonstrate Converging Medical Oncology and Urology Disciplines

December 15, 2018
Arjun V. Balar, MD

Targeted Therapies in Oncology, December 2 2018, Volume 7, Issue 13

In this editorial note from Arjun V. Balar, MD, he discusses how the KEYNOTE-57 findings have impacted the treatment landscape for Bacillus Calmette-Guérin—refractory, high-risk nonmuscle invasive bladder cancer.

Arjun V. Balar, MD

We heard a lot of exciting data presented at the European Society of Medical Oncology Congress in Munich this past October. One set of data that particularly intrigued me was the interim analysis from KEYNOTE-57—a single-arm phase II trial of pembrolizumab in patients with Bacillus Calmette-Guérin (BCG)—refractory, high-risk nonmuscle invasive bladder cancer (NMIBC).1I know what you are thinking: “Yet another trial of a PD-1 antibody in cancer—how could this be exciting?”

My answer would be that this is potentially the most impactful piece of data for this disease: NMIBC represents more than 70% of all cases every year in the United States and is a costly disease to manage. Although intravesical BCG is the standard of care for high-grade NMIBC, with up to 70% of patients with carcinoma in situ responding to treatment, a significant percentage will ultimately relapse. Subsequent treatment options (termed salvage therapy) are limited, with lower response rates and short response durations; all the while, an overarching concern involves the risk of occult progression to metastatic disease. Therefore, for patients with BCG-refractory disease, radical cystectomy is considered a standard of care, with the primary goal of removing the cancer before micrometastases develop.

Meanwhile, in more advanced disease, we’ve observed major leaps forward with cancer immunotherapy, now an established standard of care in the second- and first-line settings. Naturally, a systemic immunotherapy should be tested in the BCG-refractory setting, and the initial data are quite promising: a 38% complete response (CR) rate at 3 months and more than 80% of those CRs lasting longer than 6 months. Obviously, more follow-up will be needed, but the preliminary interpretation is that these data could be practice changing and may allow patients to keep their bladders.

What is particularly unique in this setting is the potential convergence of medical oncology and urology disciplines in managing bladder cancer like never before. Historically, NMIBC has been exclusively managed by urology from the instillations of intravesical treatments to the periodic cystoscopies, transurethral resections, and collection of urine for cytologic examination to diagnose and monitor the disease.

With the potential introduction of systemic immunotherapy, commonly the domain of medical oncologists, the field can become truly integrated. This opportunity is of paramount importance and must be executed flawlessly for the appropriate care of our patients. Without close collaboration between both disciplines, patients may run the risk of being treated with immunotherapy without the close cystoscopic monitoring necessary to know if the treatment is working or if the opposite problem is occurring: excellent vigilance of the bladder without the expertise and oversight of a specialist trained to safely administer systemic cancer treatments. Other trials are under way that may further challenge existing treatment paradigms and care provider roles in this disease. As a bladder cancer oncologist, I’m excited about the future—aren’t you?


de Wit R, Kulkarni GS, Uchio E, et al. Pembrolizumab for high-risk (HR) non—muscle invasive bladder cancer (NMIBC) unresponsive to bacillus Calmette-Guérin (BCG): phase II KEYNOTE-057 trial. Presented at: European Society of Medical Oncology 2018 Congress; October 19-23, Munich, Germany. Abstract 864O. academic.oup. com/annonc/article/29/suppl_8/mdy283.073/5140263.