From the Journals

Dose-dense MVAC credited with better bladder cancer survival



In patients with muscle-invasive bladder cancer, a dose-dense neoadjuvant chemotherapy regimen followed by cystectomy was associated with a higher rate of complete responses, compared with standard gemcitabine-platinum neoadjuvant chemotherapy and cystectomy, results of a retrospective analysis indicate.

Among 1,113 patients who underwent neoadjuvant chemotherapy (NAC) and cystectomy, a regimen of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) was associated with a nearly threefold greater likelihood that patients would have a complete response, compared with gemcitabine and cisplatin, reported Scott M. Gilbert, MD, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, and colleagues.

“We also found that ddMVAC was associated with longer survival intervals and a lower risk of death than the other treatments examined, although those findings did not reach statistical significance, indicating that larger comparative studies are needed to definitively answer questions regarding survival,” they wrote in JAMA Oncology.

The investigators noted that, despite clear evidence of a survival benefit associated with neoadjuvant chemotherapy followed by cystectomy, compared with cystectomy alone in patients with muscle-invasive bladder cancer, “the rates of adoption and routine use of NAC have been modest.”

Gemcitabine and cisplatin have become the de facto standard of care because of favorable toxicity profile and response rates comparable to those seen with ddMVAC. Yet there are few studies comparing disease control and survival outcomes for different neoadjuvant chemotherapy regimens, they noted, which prompted the current study.

The investigators conducted a cross-sectional analysis of data on 1,113 patients with bladder cancer treated with cystectomy at their center from January 2007 through May 2017. They compared rates of downstaging, complete responses, and overall survival with ddMVAC, compared with gemcitabine combined with either cisplatin or carboplatin, other neoadjuvant combinations (including etoposide- fluorouracil- and paclitaxel-based regimens) or no neoadjuvant chemotherapy.

Of the 1,113 patients, 824 had disease stage T2 or greater, and of this group, 332 had received neoadjuvant chemotherapy.

They found that ddMVAC was associated with a 52.2% downstaging rate, compared with 41.3% for gemcitabine-cisplatin, and 27% for gemcitabine-carboplatin. Respective pathologic complete response rates were 41.3%, 24.5%, and 9.4% (P less than .001).

Downstaging rates for patients treated with other regimens and patients who did not receive neoadjuvant chemotherapy were 42% and 25.7%, respectively. Complete response rates (downstaging to pT0N0) were 24% and 10.7%.

In a multivariable logistic regression model controlling for age, comorbidities, sex, clinical stage, and chemotherapy regimen, ddMVAC was associated with a significantly higher likelihood of pathologic complete response, with an odds ratio of 2.67 (P less than .001). Similarly, a propensity-score model weighted for clinical and demographic characteristics showed an OR for complete response with ddMVAC of 1.52 (P = .05).

The 2-year Kaplan-Meier survival probability estimate for ddMVAC was 73.3%, compared with 62% for gemcitabine-cisplatin and 34.8% for gemcitabine-carboplatin (P = .002).

Regardless of chemotherapy type, a complete pathologic response was a significant predictor for overall survival (P less than .001).

Although ddMVAC showed a trend toward better overall survival in both logistic regression and propensity score models, neither reached statistical significance.

The authors did not report survival results for patients who did not receive neoadjuvant chemotherapy.

The investigators acknowledged that the study is limited by its nonrandomized design and the relatively small sample of patients treated with ddMVAC (46 patients).

The study was supported in part by a National Cancer Institute grant to the H. Lee Moffitt Cancer Center. The authors reported having no conflicts of interest.

SOURCE: Peyton CC et al. JAMA Oncology. 2018 Aug 30. doi: 10.1001/jamaoncol.2018.3542.

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