Gemcitabine-Docetaxel Effective Alternative to BCG in NMIBC

For patients with high-risk non–muscle-invasive bladder cancer (NMIBC), the gold-standard systemic therapy for preventing disease recurrence and progression following transurethral resection is bacillus Calmette-Guérin (BCG).

However, BCG has been in short supply for some years now, because of supply chain problems, and as previously reported by Medscape Medical News, urologic oncologists worldwide have been casting about for effective and safe alternatives.

Now, investigators from the University of Iowa report on their experience using sequential intravesical gemcitabine and docetaxel following transurethral resection of bladder tumors in patients with high-risk NMIBC, and compared the outcomes in a retrospective cohort study with those of similar patients treated with BCG.

They found that the chemotherapy combination performed as well or better than BCG and was associated with a lower risk of high-grade disease recurrence. In addition, the discontinuation rate after induction was significantly higher for patients started on BCG than on gemcitabine-docetaxel.

“These findings suggest that, while awaiting results from an ongoing randomized clinical trial during the current BCG shortage, use of gemcitabine and docetaxel can be considered for recommendation in updated practice guidelines,” write investigators Ian M. McElree, MS, and colleagues from the University of Iowa in Iowa City.

Their study was published online February 28 in JAMA Network Open.

In an interview with Medscape Medical News, senior author Vignesh T. Packiam, MD, said that he is confident about the benefits of sequential gemcitabine-docetaxel in patients with high-risk NMIBC.

“There is a good amount of high-quality evidence comparing BCG to single-agent chemotherapy, which for the most part has shown that BCG is superior to all of these agents,” he said. “We developed this dual combination chemotherapy regimen initially to treat patients who had recurrence after BCG, but given the BCG shortage, we moved it up in the timeline to become a first treatment, and we were pleasantly surprised with how effective it is in that situation.”

Head-to-Head Trial in the Works

Although Packiam and colleagues are currently participating in a head-to-head randomized trial comparing the two treatment approaches in patients with NMIBC, the results of that trial are not expected for several years, so in the interim they conducted the retrospective study that has just been published.

The team looked at data on 174 patients with high-risk treatment naive NMIBC who received BCG and 138 who received gemcitabine-docetaxel from January 2011 through December 2021.

The median durations of follow-up were 49 and 23 months, respectively.

All patients underwent complete transurethral resection of bladder tumors, followed by either sequential intravesical gemcitabine 1 g and docetaxel 37.5 mg, or 1 vial of BCG.

High RFS Rates With Chemotherapy

For patients treated with BCG the estimated rates of high-grade, recurrence-free survival (RFS) were 76% at 6 months, 71% at 12 months, and 69% at 24 months.

For patients who received the combination, the respective estimated RFS rates were 92%, 85%, and 81% at 6, 12, and 24 months.

In multivariable regression analyses controlling for age, sex, treatment year, and presence or absence of carcinoma in situ, the chemotherapy combination was associated with both better high-grade RFS (hazard ratio [HR] for recurrence, 0.57; P = .04) and overall RFS (HR, 0.56; P = .02) than BCG.

The authors reported that patients generally tolerated the chemotherapy combination well. Significantly more patients started on BCG discontinued their therapy than patients who started on gemcitabine-docetaxel (9.2% vs 2.9%, P = .02).

“We were able to compare gemcitabine-docetaxel to BCG in a fairly well-matched population, and we found that the efficacy is equal if not better than BCG. The caveat is that this has to be confirmed prospectively” Packiam told Medscape.

As noted before, Packiam and his team are participating in the randomized phase 3 BRIDGE trial, which is testing the hypothesis that patients with BCG-naive NMIBC who are treated with intravescial gemcitabine and docetaxel with have non-inferior, event-free survival compared with patients treated with BCG.

The study was supported by the Holden Comprehensive Cancer Center, John and Carol Walter Family Foundation and the University of Iowa Carver College. Packiam reported having no relevant conflicts of interest.

JAMA Netw Open. Published online February 24, 2023. Full text

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.

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