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Outcomes With Neoadjuvant Chemotherapy Regimens in Muscle-Invasive Bladder Cancer

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Key Points

  • Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddVAC) was associated with greater downstaging and complete pathologic response rates vs gemcitabine/cisplatin.
  • Overall survival was numerically better with ddMVAC than with other neoadjuvant regimens.

In a single-center analysis reported in JAMA Oncology, Peyton et al found that neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) produced better outcomes than other standard neoadjuvant regimens in patients undergoing radical cystectomy for muscle-invasive bladder cancer.

Study Details

The study involved 824 patients with muscle-invasive disease who underwent cystectomy at the Moffitt Cancer Center between January 2007 and May 2017. Of them, 332 (40%) received neoadjuvant chemotherapy, including gemcitabine/cisplatin in 204, gemcitabine/carboplatin in 32, ddMVAC in 46, and other regimens in 50.

Downstaging and Complete Response

Downstaging rates were 52.2% with ddMVAC, 41.3% with gemcitabine/cisplatin, and 27.0% with gemcitabine/carboplatin, and the rates of complete pathologic response were 41.3%, 24.5%, and 9.4%, respectively (overall P < .001 for both). In an analysis adjusting for age, comorbidity, sex, clinical stage, and chemotherapy regimen, downstaging was significantly more likely with ddMVAC vs gemcitabine/cisplatin (odds ratio [OR] = 1.84, 95% confidence interval [CI] = 1.10–3.09), as was complete response (OR = 2.67, 95% CI = 1.50–4.77). Similar results were seen on propensity score–matching analysis for downstaging (OR = 1.62, 95% CI = 1.05–2.50) and complete response (OR = 1.52, 95% CI = 0.99–2.35).

Estimated 2-year overall survival was 73.3% with ddMVAC, 62% with gemcitabine/cisplatin, and 34.8% with gemcitabine/carboplatin (overall P = .002). However, the difference between ddMVAC and gemcitabine/cisplatin was not signifcant on multivariate (HR = 0.42, P = .07) or propensity score–matching analysis (HR = 0.44, P = .16).

The investigators concluded, “This study suggests that neoadjuvant ddMVAC followed by cystectomy is associated with a higher complete response (ypT0N0) rate than standard [neoadjuvant chemotherapy]. These data highlight and suggest the need to further investigate ddMVAC vs standard [neoadjuvant chemotherapy] in a prospective, randomized fashion.”

The study was supported by the National Cancer Institute.

Scott M. Gilbert, MD, of the H. Lee Moffitt Cancer Center and Research Institute, is the corresponding author of the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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