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Pembrolizumab Monotherapy Promising For BCG-Unresponsive NMIBC

Phase II trial results point to the benefit of pembrolizumab in patients with BCG-unresponsive carcinoma in situ, with or without papillary tumours, who are ineligible for or decline surgery
04 Jun 2021
Immunotherapy
Urothelial Cancer

Author: By Shreeya Nanda, Senior medwireNews Reporter 

 

medwireNews: Single-agent pembrolizumab has antitumour activity and a manageable safety profile in patients with non-muscle-invasive bladder cancer (NMIBC), with or without papillary tumours, that is unresponsive to Bacillus Calmette-Guérin (BCG), suggest KEYNOTE-057 trial findings. 

On the basis of interim results from the phase II trial, the US FDA approved the PD-1 inhibitor for patients “who are ineligible for or choose not to undergo radical cystectomy”, write the investigators in The Lancet Oncology

This approval “represents a substantial advancement in a difficult-to-treat disease setting with few approved therapeutic options”, says the team, adding that the decision “establishes a foundation and benchmark for future trials that could provide higher and more durable responses” in this patient population. 

Arjun Balar, from NYU Langone Health in New York, USA, and collaborators report on cohort A of the study, which included 101 patients with carcinoma in situ, with or without papillary tumours, five of whom were not included in the efficacy analysis as they did not fulfil FDA criteria for BCG-unresponsive NMIBC. 

Treatment with pembrolizumab 200 mg every 3 weeks led to a complete response – defined as the absence of high-risk or progressive disease – in 41% of the 96 evaluable patients at 3 months. The median duration of response was 16.2 months, and just under half (46%) of the 39 responders had a response that lasted at least 12 months. 

The study authors also note that 28% of the patients with a complete response “continued to be followed up for efficacy and had an ongoing response at the time of data cutoff”, which occurred at a median follow-up of 36.4 months. 

The estimated 12-month progression-free survival (PFS) rate was 83% when progression was defined as worsening of grade or stage or death, while the rate was 97% when progression was defined as muscle-invasive or metastatic disease or death. The median PFS times as per each definition were unreached and 39.9 months, respectively. 

Median overall survival was not reached at the time of analysis, and the estimated 12-, 24- and 36-month rates were 98%, 95% and 91%, respectively. 

Reporting on the safety, the investigators note that “pembrolizumab monotherapy had a manageable safety profile consistent with that previously reported, and no new risks associated with its use were identified.” 

Thirteen patients experienced treatment-related adverse events (TRAEs) of grade 3 or 4, with hyponatraemia and arthralgia the most common events, occurring in three and two patients, respectively. Serious TRAEs were observed in eight patients, while three participants reported immune-mediated AEs of grade 3–4. 

A total of 13% of patients required a pembrolizumab dose interruption due to TRAEs and 7% discontinued as a result. But there were no treatment-related deaths during the course of the study. 

“This single-arm study is limited by the absence of a direct comparator group”, say Arjun Balar and co-authors, but they emphasize that “few efficacious treatment options other than radical cystectomy are available for this patient population.” 

The researchers therefore believe that pembrolizumab “should be considered a clinically active non-surgical treatment option in this difficult-to-treat population.” 

And they conclude: “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.” 

Reference  

Balar AV, Kamat AM, Kulkarni GS, et alPembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol; Advance online publication 26 May 2021. doi: 10.1016/ S1470-2045(21)00147-9

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2021 Springer Healthcare part of the Springer Nature group

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