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SAN DIEGO -- The use of sequential intravesical gemcitabine and docetaxel appeared effective and well tolerated in patients with high-risk non-muscle invasive bladder cancer (NMIBC) following the failure of bacillus Calmette-Guérin (BCG) therapy, a retrospective study showed.

At a median follow-up of 18 months, the 6-, 12-, and 24-month high-grade recurrence-free survival (RFS) rates among 102 patients were 78%, 65%, and 49%, respectively, reported Kendrick Yim, MD, of Brigham and Women's Hospital in Boston, in a poster presentation at the Society of Urologic Oncology annual meeting.

Those rates are "pretty good in comparison with other options, such as pembrolizumab [Keytruda]," Yim told 番茄社区app.

He also noted that when looking at high-grade RFS by BCG failure group, patients with BCG-refractory disease were less likely to benefit from the combination treatments.

Specifically, patients who were BCG-refractory had 6-, 12-, and 18-month high-grade RFS rates of 72%, 55%, and 37%, respectively, compared with 84%, 81%, and 62% for patients who were BCG-relapsing, resulting in a hazard ratio of 2.14 (95% CI 1.02-4.49, P=0.04).

"So, what we think is that patients who are BCG-refractory may be better suited for upfront radical cystectomy, rather than trialing additional intravesical therapy," Yim said. "That sort of clinical information can help when you are counseling your patients, because they've already failed the standard of care."

He noted that although BCG is the standard of care for high-risk NMIBC, "for those patients who end up failing BCG, there's not much we can offer them." Radical cystectomy is the alternative with the best oncologic outcomes, but comes with significant morbidity, he explained, adding that many patients are poor candidates for surgery.

For over 20 years, valrubicin had been the only approved treatment for BCG-unresponsive disease, which the FDA has designated as an area of need. While pembrolizumab has been approved to treat patients in this setting, "long-term results have not been as durable," Yim said. "So we were asking what other solutions are available."

He pointed out that research teams at Massachusetts General Hospital and the University of Iowa have demonstrated that the combination of gemcitabine/docetaxel is promising in treating NMIBC. Thus, this multi-institutional study was designed to look at the safety, efficacy, and long-term effects of the combination.

The study included 102 patients (median age 72 years) with high-risk NMIBC who met the criteria for BCG failure (BCG refractory, relapsing, or intolerant) and were treated with induction intravesical gemcitabine/docetaxel.

Overall RFS rates were 74%, 63%, and 38% at 6, 12, and 24 months. Twenty patients underwent radical cystectomy at a median 15.5 months from induction, and six patients progressed to muscle invasion.

"In terms of tolerability, all 102 patients were able to complete at least five of six courses, so it was very well tolerated, while the most common adverse events were urinary frequency [41%] and dysuria [21%]," Yim said.

As for future research, Yim said that he and his team have received funding to do a genomic analysis. "So, we'll do a study looking at whether there are any genomic biomarkers telling us who will and will not respond based on genomic analysis of that transurethral resection specimen."

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