The FDA has approved a gemcitabine intravesical system for Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), either with or without papillary tumors, for patients who refuse or are ineligible for bladder removal. 

The new system (Inlexzo, Johnson & Johnson) consists of a flexible, dual lumen silicone tube carrying 225 mg of sustained release gemcitabine. It is inserted into the bladder through a catheter where it coils into a pretzel shape and remains in the bladder releasing gemcitabine for 3 weeks. Treatment can be repeated up to 14 times. 

Insertion takes a few minutes in a urologist’s office and doesn’t require general anesthesia, J&J said in a press release.

Approval was based on cohort 2 of the single-arm SunRISe-1 trial; 83 patients were treated every 3 weeks for 6 months, followed by once every 12 weeks for up to 18 months. Tumor status was assessed with cystoscopy, urine cytology, and biopsy.

The study’s major efficacy outcome measures were complete response (CR) at any time and duration of response. The CR rate was 82%, with 51% of patients remaining in CR for 12 or more months. Seven patients (8%) progressed to muscle invasive bladder cancer. The median time between persistent or recurrent CIS or T1 and progression to muscle invasive disease was 94 days, according to the J&J press release.

NMIBC with CIS makes up about 10% of NMIBC cases. Radical cystectomy is the current standard of care for BCG-unresponsive disease. 

Lower Response Rate Seen With Other Intravesical Treatment

Sequential intravesical gemcitabine/docetaxel (Gem/Doce) is another option for patients who refuse or are ineligible for cystectomy, but initial response rates with this drug and method combination were lower than in SunRISe-1. 

In that trial, 97 patients, of which 35% had BCG-unresponsive disease, received six weekly intravesical Gem/Doce instillations for high-risk NMIBC after BCG failure. At 3-month surveillance, 74% of patients had CR, with the median duration of response having been 25 months.

The outcomes of this study of sequential intravesical Gem/Doce included high-grade recurrence-free survival (HG-RFS), progression-free survival (PFS), cystectomy-free survival (CFS), cancer-specific survival (CSS), and overall survival (OS). At 1, 2, and 5 years, HG-RFS was 60%, 50%, and 30%, respectively. Five-year PFS, CFS, CSS, and OS were 82%, 75%, 91%, and 64%, respectively.

Expert Takes and Side Effects

“I see many patients that ultimately become BCG-unresponsive and often face life-altering bladder removal. These patients now may be ideal candidates for newly approved Inlexzo,” principal investigator Siamak Daneshmand, MD, a urologist at the University of Southern California, Los Angeles, said in the press release. 

“This will change the way we treat appropriate patients that haven’t responded to traditional therapy,” Daneshmand continued. 

The most common side effects, occurring in 15% or more of patients, were urinary frequency, urinary tract infection, dysuria, micturition urgency, decreased hemoglobin, increased lipase, urinary tract pain, decreased lymphocytes, hematuria, increased creatinine, increased potassium, increased aspartate aminotransferase, decreased sodium, bladder irritation, and increased alanine transaminase.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com