KEYNOTE-057 supports pembrolizumab for BCG-unresponsive bladder cancer
medwireNews: The PD-1 inhibitor pembrolizumab shows promising antitumor activity in people with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with or without papillary tumors, show data from the phase 2 KEYNOTE-057 trial.
Writing in The Lancet Oncology, Arjun Balar (NYU Langone Health, New York, USA) and co-authors explain that interim results from KEYNOTE-057 “led to FDA approval of pembrolizumab” in patients who are either ineligible for or decline radical cystectomy.
They say that this approval “fulfils a major unmet need and establishes a foundation and benchmark for future trials that could provide higher and more durable responses for patients with BCGunresponsive carcinoma in situ with or without papillary tumours.”
In the current analysis, the researchers provide further data for the 101 participants who were treated with pembrolizumab 200 mg every 3 weeks for up to 24 months or until disease persistence, recurrence, or progression, unacceptable toxic effects, or withdrawal of consent.
At 3.0 months, 41% of 96 patients had a complete response to treatment, defined as the absence of high-risk NMIBC or progressive disease, with a median response duration of 16.2 months. Five patients were excluded from the efficacy analysis because their disease did not meet the US FDA definition of BCG-unresponsive NMIBC.
Among the responders, 28% had an ongoing response at the time of data cutoff (>2 years).
At 12 months, the estimated progression-free survival rate was 83% when defined as worsening of grade or stage or death and 97% when defined as progression to muscleinvasive or metastatic disease or death, with median durations of each outcome not reached and 39.9 months, respectively.
Overall survival was 98% at 12 months, 95% at 24 months, and 91% at 36 months.
Balar and team report that the treatment had a safety profile that “was manageable and consistent with previous reports of pembrolizumab monotherapy.”
Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 13 patients, most commonly hyponatremia (n=3) and arthralgia (n=2). Eight patients had serious TRAEs and three experienced grade 3 or 4 immune-mediated AEs. There were no treatment-related deaths.
The researchers also note that healthrelated quality of life, assessed using the Functional Assessment of Cancer Therapy–Bladder Cancer questionnaire, remained stable throughout treatment.
Balar et al conclude that their data “support the use of pembrolizumab as a clinically active non-surgical treatment option in patients with BCG-unresponsive carcinoma in situ of the bladder who are ineligible for or decline radical cystectomy.”
They add: “Future trials should explore potential markers and mechanisms of resistance to identify patients who are most likely to respond to PD-1 or PD-L1 immunotherapy. Combination strategies should also be considered to further improve upon the action of pembrolizumab.”
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