Amid drug shortage, chemotherapy regimen a viable alternative for high-risk bladder cancer
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Key takeaways:
- Gemcitabine and docetaxel conferred a numerically superior RFS rate than BCG at every time point evaluated.
- Practices should update their infrastructure and workflows to accommodate the additional option.
The combination of gemcitabine and docetaxel conferred superior high-grade recurrence-free survival compared with standard therapy among adults with high-risk nonmuscle-invasive bladder cancer, results of a retrospective study showed.
Patients who received the chemotherapy combination also had a lower frequency of treatment discontinuation than those who received bacillus Calmette-Guérin (BCG), according to findings published in JAMA Network Open.
“Especially given the ongoing shortage, there is mounting evidence that gemcitabine and docetaxel is an equal if not better option to treatment with BCG,” Vignesh T. Packiam, MD, clinical assistant professor of urology at University of Iowa Health Care, told Healio.
Background
A worldwide shortage of BCG has been “intermittent and ongoing” for several years, but regardless of supply, there is a large subset of patients with high-risk nonmuscle-invasive bladder cancer for whom it is not effective, Packiam said.
“There is a significant unmet need for an effective intravesical option for patients whose tumors do not respond well to BCG,” he told Healio.
In response to ongoing shortages of BCG, Packiam’s colleague, Michael O'Donnell, MD, Richard D. Williams chaired professor of urology at University of Iowa, began using the combination of gemcitabine and docetaxel for patients with high-risk nonmuscle invasive bladder cancer more than a decade ago. O’Donnell’s group published a paper in 2015 demonstrating its effectiveness, including for a subset of patients who had complete responses to the chemotherapy regimen.
But the study had several limitations, including its single-center nature, small sample size and relatively homogeneous population, Packiam added.
“As the BCG shortage got worse over time, we started using the regimen more out of necessity,” he said. “Anecdotally, we noticed that this combination worked as well if not better than BCG.”
Methodology
Packiam and colleagues conducted a retrospective cohort study to determine the safety and efficacy of gemcitabine and docetaxel compared with BCG in adults with high-risk, treatment-naive nonmuscle-invasive bladder cancer.
The investigators examined data from 312 patients (median age, 73 years; interquartile range [IQR], 66-79; 81.7% men; 93.6% white) seen at University of Iowa’s tertiary care center, including 174 who received BCG therapy and 138 who received the gemcitabine and docetaxel regimen.
All study participants underwent complete transurethral resection of their bladder tumor followed by induction therapy once per week for 6 weeks with either one vial of BCG or sequential intravesical gemcitabine dosed at 1 g and docetaxel dosed at 37.5 mg.
Patients received additional maintenance treatments if they remained disease free at their first follow-up assessment.
High-grade recurrence-free survival (RFS) served as the study’s primary outcome. Secondary outcomes included safety in terms of treatment-related adverse events.
Patients in the gemcitabine and docetaxel group had median follow-up of 23 months (IQR, 12-33), whereas those who received BCG had median follow-up of 49 months (IQR, 27-79).
Key findings
Patients who received a combination of gemcitabine and docetaxel had numerically superior RFS rates at every time point evaluated in the analysis.
The investigators noted estimated high-grade RFS rates of 76% (95% CI, 69-82) at 6 months, 71% (95% CI, 64-78) at 12 months and 69% (95% CI, 62-76) at 24 months for the BCG group compared with 92% (95% CI, 86-95) at 6 months, 85% (95% CI, 78-91) at 12 months, and 81% (95% CI, 72-87) at 24 months in the gemcitabine and docetaxel group.
Multivariate analysis controlled for factors such as age, sex, treatment year and carcinoma in situ showed gemcitabine and docetaxel conferred significantly better high-grade RFS (HR = 0.57; 95% CI, 0.33-0.97) and RFS (HR = 0.56; 95% CI, 0.34-0.92) than BCG.
Researchers also reported a significantly higher treatment discontinuation rate among those who received BCG vs. gemcitabine and docetaxel (9.2% vs. 2.9%; P=.02)
Clinical implications
“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,” Packiam and colleagues wrote.
Positive results from the phase 3 BRIDGE trial are needed to ultimately change the standard of care for this group of patients with nonmuscle-invasive bladder cancer, Packiam said. The ongoing randomized study will compare BCG with gemcitabine and docetaxel after complete transurethral resection. The multicenter trial includes more than 800 patients, but results are likely to take up to 5 years or more, Packiam noted.
Because of the ongoing BCG shortage and results seen thus far, Packiam advises that practices update their infrastructure and workflows to accommodate the additional treatment.
"Many practices have already begun to do that, and this will be the next step for who are not using this option already," he said.
References:
- McElree IM, et al. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2023.0849.
- Steinberg RL, et al. Bladder Cancer. 2015;doi:10.3233/BLC-150008.
For more information:
Vignesh T. Packiam, MD, can be reached at University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242; email: vignesh-packiam@uiowa.edu; Twitter: @VigneshPackiam.
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