Keytruda May Play a Role in Treatment of Patients with Non-Muscle Invasive Bladder Cancer

After patients with non—muscle invasive bladder cancer fail to respond to treatment with Bacillus Calmette-Guérin (BCG) immunotherapy, Keytruda (pembrolizumab) may induce responses in these high-risk patients, according to Arjun V. Balar, M.D.

At the 2019 Genitourinary Cancers Symposium, Balar — who is director of the genitourinary medical oncology program at NYU Langone’s Perlmutter Cancer Center – presented findings from the phase 2 KEYNOTE-057 study, designed to evaluate the efficacy of Keytruda in patients with high-risk disease who previously received BCG and became unresponsive to the treatment.

Balar sat down with OncLive, a sister publication of CURE’s, to discuss the study findings and what this means for BCG — a therapy that has been around for more than 40 years to treat bladder cancer.

OncLive: What was the rationale for this study?

Balar: KEYNOTE-057 aimed to test (Keytruda), which is a PD-1 antibody in a specific population of patients with non—muscle invasive bladder cancer. And these are patients with high-risk disease and received BCBG in the past, which is an intravesical immunotherapy, and that are now considered unresponsive to BCG therapy. This population historically is treated with radical cystectomy, which means surgical removal of the bladder. And the reason we do this is because BCG unresponsive disease, the natural history progressed to muscle invasive and potentially metastatic disease. Radical cystectomy historically has been the only curative therapy for these patients. It is in this context that (Keytruda) was tested hopefully as a means to achieve responses in the bladder and help patients preserve their bladders.

What were the findings?

(I presented) a preliminary analysis of 102 patients who are enrolled in cohort A. Specifically this trial focused on two cohorts. Cohort A focused on patients with carcinoma in situ with or without papillary disease and cohort B focused on patients with papillary disease alone without carcinoma in situ. So, specifically we’re looking at cohort A which includes patients with CIS. Findings at this point with 102 patients and a median follow-up of around 16 months is that the complete response rate in the bladder with (Keytruda) is 40 percent. Additionally, with the median follow-up at this point, we show that the median duration of response is about 12.5 months, and about 53 percent of patients will have (complete responses) that are lasting nine months or longer, which is quite encouraging. But of course, it is early data and longer-term follow-up will be necessary.

What are the next steps?

The next steps for this trial are obviously to follow up these patients who have achieved a (complete response) and truly how long and durable these responses are. It is also worthy that this needs to be tested in a randomized setting. That is what KEYNOTE-676 is aiming to do. It is the confirmatory phase 3 trial for this particular study. While this study has the potential to have registrational implications for (Keytruda) in this population, the randomized phase 3 (trial) is important as well. That will focus on patients with BCG-refractory disease after induction BCG and will be randomizing patients to either BCG reintroduction on its own or BCG reintroduction along with (Keytruda).

Will BCG always have a role in treatment for these patients?

BCG has a long-standing history in the treatment of non—muscle invasive bladder cancer. I believe that it will actually have a firm role for decades to come largely because it is still very active. In fact, 70 percent of patients with carcinoma in situ will achieve complete response to BCG, so it is very effective. What I see as my vision in the future is not so much that BCG gets replaced; however, BCG will potentially get augmented with other immune synergizing agents, and potentially PD-1 antibodies.