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Lead Investigator Highlights Pembrolizumab Potential in BCG-Resistant Bladder Cancer

Brandon Scalea
Published: Friday, Nov 02, 2018

Ronald de Wit MD, PhD
Ronald de Wit MD, PhD
Pembrolizumab (Keytruda) demonstrated durable activity in patients with high-risk nonmuscle–invasive bladder cancer (NMIBC) who were resistant to Bacillus Calmette-Guérin (BCG), according to an interim analysis from the single-arm, open-label, phase II KEYNOTE-057 trial.

at the 2018 ESMO Congress, de Wit discussed the clinical implications of pembrolizumab in this NMIBC patient population.

OncLive: Please provide an overview of the KEYNOTE-057 trial.

DeWit: I presented the interim results of an ongoing study testing the efficacy and duration of response of pembrolizumab in patients with NMIBC at high risk for disease progression and who were unresponsive to BCG therapy. The data I presented were from cohort A, which was a high-risk population. We had a data cut-off of April 1, 2018, to ensure a sufficient follow-up time for this interim analysis. At that time, we had enrolled 103 patients, and I presented on these patients.

These results are encouraging, and we have to realize the only other option for these patients is radical cystectomy. This procedure has morbidity and mortality, and it is associated with adverse quality of life. Some patients even refuse that procedure or are ineligible for that procedure. This is an important new avenue for treatment, especially if we can preserve the bladder for these patients.

What is the difficulty in treating this patient population?

Historically, we know that in high-risk NMIBC, about one-third of patients have disease recurrence within 1 year. If not properly treated, 40% will ultimately have MIBC and then the risk of dying from metastatic disease. This is not a benign disease. If patients recur after being treated with BCG, the next step is radical cystectomy. This is the patient population we are talking about. They need a treatment that will allow them to keep their bladder and eliminate that risk of dying from the disease.

Will immunotherapy eventually have a bigger role in bladder cancer?

The use of checkpoint inhibition is obvious in bladder cancer, similar to other diseases, such as melanoma and lung cancer. It has to do with the mutational profile of these diseases. We know of the survival benefit for second-line immunotherapy following platinum-based therapy [in bladder cancer]. Pembrolizumab has evidence of providing survival benefit, particularly for frontline treatment of cisplatin-ineligible patients.

In PD–L1-positive patients, the median OS for patients was 18 months. Just for comparison, we know the median OS for patients treated with gemcitabine was 9 months. We are seeing robustly better results with immunotherapy.

What is the take-home message of KEYNOTE-057?

First of all, we have to realize, as medical oncologists, that NMIBC is not a benign disease. It really needs adequate treatment. Based on these encouraging results we presented, I would suggest patients be referred to the sites that will be accruing in the upcoming study of BCG with or without pembrolizumab.
De Wit R, Kulkarni G, Uchio E, et al. Pembrolizumab for high-risk (HR) non–muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG): phase 2 KEYNOTE-057 trial. Presented at ESMO 2018; October 19-23, Munich, Germany. 864O.



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