Non-Muscle Invasive Bladder Cancer: Difference between revisions

==== 2021 CUA ====

 

'''Contraindications'''

* '''<span style="color:#ff0000">See</span> [[CUA/AUA: Non-muscle Invasive Bladder Cancer (2021 CUA/2016 AUA))|2016 AUA/2021 CUA NMBIC]] <span style="color:#ff0000">Guideline Notes</span>'''

*# '''<span style="color:#ff0000">Single-agent intravesical therapy (MMC, epirubicin, docetaxel, gemcitabine)'''

* '''<span style="color:#ff0000">Pembrolizumab'''

** Systemic immunotherapy for NMIBC

** '''MOA: PD-1 checkpoint inhibitor'''

** Dose: 200 mg IV q3weeks for up to 24 months

** '''<span style="color:#ff00ff">KEYNOTE-057 (Lancet Oncology 2021)'''

*** Population: 96 patients with BCG-unresponsive CIS who were ineligible for or declined to undergo radical cystectomy

****BCG-unresponsive disease was defined as

*****Stage progression at 3 months (or up to 4 weeks either side) despite adequate BCG induction therapy alone OR

*****Persistent high-risk non-muscle-invasive bladder cancer at 6 months (or up to 4 weeks either side) after adequate BCG therapy OR

*****Recurrent high-risk non-muscle-invasive bladder cancer within 9 months after the last BCG instillation despite adequate BCG therapy.

*** '''Single arm study''': 200 mg of pembrolizumab IV q3 weeks for 24 months or until recurrence, progression or limiting toxicity

*** Primary outcome: clinical complete response rate (absence of high-risk non-muscle-invasive bladder cancer or progressive disease), assessed by cystoscopy and urine cytology approximately 3 months after the first dose of study drug.

*** Results

**** Median follow-up: 36.4 months

**** Complete response in 39 patients (41%) at 3 months

**** Median duration of response was 16.2 months

****Median duration of treatment was 4.2 months

*****91% discontinued treatment; primary reasons for discontinuation were persistent disease and recurrent disease or stage progression to T1 disease

****49% of initial responders and non-responders who discontinued pembrolizumab subsequently underwent radical cystectomy

**** Adverse events

*****Treatment-related adverse events in 66% of patients

******13% of patients had grade 3 or 4 treatment-related adverse events

******22% of patients had immune-related adverse events of any grade

*****Most common treatment-related adverse events: hyponatremia (3%), arthralgia (2%)

*****Most common serious treatment-related adverse events: pneumonitis (3%), colitis (2%)

*****Treatment-related adverse events led to pembrolizumab interruption in 13% of patients

*** [https://pubmed.ncbi.nlm.nih.gov/34051177/ Balar, Arjun V., et al.] "Pembrolizumab 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." ''The Lancet Oncology'' (2021).

* '''<span style="color:#ff0000">Nadofaragene firadenovec (Adstiladrin)</span>'''

** MOA: a non-replicating adenovirus vector (rAd-INFa/Syn3) together with recombinant IFN-alpha2b. When given intravesically, the virus is transduced into bladder cells and the IFN-alpha2b gene is incorporated by the DNA. IFNalpha2b protein, which has antitumour activity, is then produced.

*** '''<span style="color:#ff00ff">Single-arm trial</span>'''

*** Population: 157 patients with BCG-unresponsive non-muscle-invasive bladder cancer

*** Results:

**** 53% of patients with (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 46% of 55 patients at 12 months.

*** [https://pubmed.ncbi.nlm.nih.gov/33253641/ Boorjian, Stephen A., et al.] "Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial." ''The Lancet Oncology'' 22.1 (2021): 107-117.

* '''Oportuzumab monatox (Vicineum)'''

** MOA: specific antibody to Epithelial Cell Adhesion Molecule (EpCAM) fused to a Pseudomonas toxin that binds specifically to bladder cancer cells.

* '''BCG plus N-803'''

** MOA: N-803 is an IL-15 superagonist antibody cytokine fusion protein that can be co-administered intravesically with BCG to induce activation and proliferation of endogenous natural killer (NK) cells and CD8+ T-cells without inducing a T-reg response.