Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, with Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients with Bladder Cancer

Maase, Hans von der; Sengeløv, Lisa; Roberts, J.T.; Ricci, Sergio; Dogliotti, Luigi; Oliver, T.; Moore, Malcom J.; Zimmermann, Anna; Arning, M.

doi:10.1016/s0022-5347(05)00370-8

Cited by 295 publications

(440 citation statements)

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Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15] The overall survival rates are 7% for patients with visceral metastases and 21% for patients without visceral metastases. 15 Although multiple first-and second-line chemotherapy regimens are available, most often using a platin-containing regimen, the efficacy is limited Urothelial carcinoma DNA sequencing and the toxicity is significant. [12][13][14][15] The emergence of the significantly less toxic therapies that target the GA driving an individual patient's disease have produced major responses and prolongation of survival for non-small-cell lung cancer and other solid tumor patients, clearly positively impacting the clinical outcome of disease.…”

Section: Discussionmentioning

confidence: 99%

“…15 Although multiple first-and second-line chemotherapy regimens are available, most often using a platin-containing regimen, the efficacy is limited Urothelial carcinoma DNA sequencing and the toxicity is significant. [12][13][14][15] The emergence of the significantly less toxic therapies that target the GA driving an individual patient's disease have produced major responses and prolongation of survival for non-small-cell lung cancer and other solid tumor patients, clearly positively impacting the clinical outcome of disease. The purpose of this study was to search for GA that permit the application of targeted therapy in a series of 35 relapsed UC cases with a single comprehensive NGS-based diagnostic assay encompassing the deep sequencing of hundreds of cancer-related genes at a high, uniform depth of coverage.…”

Section: Discussionmentioning

confidence: 99%

“…6,11 Although many patients with metastatic UC respond to the cytotoxic chemotherapy regimens used for this disease, a significant number of relapsed and metastatic UC are either resistant to the non-targeted systemic chemotherapy at the time systemic therapy begins or develop resistance to chemotherapy over time. [12][13][14][15] Characterization of the genomic drivers of UC development and progression has long been of interest to cancer biologists, urologists, genitourinary oncologists and pathologists. [16][17][18][19][20] Protein expression studies mostly performed on formalinfixed, paraffin-embedded (FFPE) specimens using immunohistochemistry (IHC) have been widely used to predict prognosis.…”

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confidence: 99%

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Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy

Wang²,

et al. 2014

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Although urothelial carcinoma (UC) of the urinary bladder generally portends a favorable prognosis, metastatic tumors often follow an aggressive clinical course. DNA was extracted from 40 lm of formalin-fixed, paraffinembedded (FFPE) sections from 35 stage IV UCs that had relapsed and progressed after primary surgery and conventional chemotherapy. Next-generation sequencing (NGS) was performed on hybridization-captured, adaptor ligation-based libraries for 3320 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer to at an average sequencing depth of 1164 Â and evaluated for all classes of genomic alterations (GAs). Actionable GAs were defined as those impacting the selection of targeted anticancer therapies on the market or in registered clinical trials. A total of 139 GAs were identified, with an average of 4.0 GAs per tumor (range 0-10), of which 78 (56%) were considered actionable, with an average of 2.2 per tumor (range 0-7). Twenty-nine (83%) cases harbored at least one actionable GA including: PIK3CA (9 cases; 26%); CDKN2A/B (8 cases; 23%); CCND1 (5 cases; 14%); FGFR1 (5 cases; 14%); CCND3 (4 cases; 11%); FGFR3 (4 cases; 11%); MCL1 (4 cases; 11%); MDM2 (4 cases; 11%); EGFR (2 cases, 6%); ERBB2 (HER2/neu) (2 cases, 6%); NF1 (2 cases, 6%) and TSC1 (2 cases, 6%). Notable additional alterations included TP53 (19 cases, 54%) and RB1 (6 cases; 17%). Genes involved in chromatin modification were altered by nonsense mutation, splice site mutation or frameshift indel in a mutually exclusive manner in nearly half of all cases including KDM6A (10 cases; 29%) and ARID1A (7 cases; 20%). Comprehensive NGS of 35 UCs of the bladder revealed a diverse spectrum of actionable GAs in 83% of cases, which has the potential to inform treatment decisions for patients with relapsed and metastatic disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy

Wang²,

et al. 2014

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“…[4][5][6] In 2000, the results from a randomized phase 3 trial were published comparing gemcitabine plus cisplatin (GC) with standard MVAC in patients with metastatic bladder cancer. 7,8 GC was associated with similar efficacy compared with MVAC, albeit with less toxicity, leading to the adoption of this regimen as among the most commonly used systemic treatments for patients with metastatic disease. 9 Pragmatically, yet in somewhat of a departure from the evidence-based oncology paradigm, the results from that trial also have been used to justify the routine use and integration into practice guidelines of neoadjuvant GC, despite a lack of prospective randomized data in this setting.…”

Section: Introductionmentioning

confidence: 99%

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer

Galsky

Pal

Chowdhury

et al. 2015

Cancer

166

101

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BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC. RESULTS: In total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P 5.77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P 5.48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice.

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The impact of eligibility for maintenance immunotherapy on prognosis in patients with unresectable or metastatic urothelial carcinoma

Ozaki

Tanaka

Noro³

et al. 2021

BJUI Compass

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Objectives To investigate the eligibility for maintenance immunotherapy and its impact on the prognosis of advanced urothelial carcinoma treated with first‐line chemotherapy, as the selection biases of the eligible population in the JAVELIN Bladder 100 trial remain unclear. Methods We retrospectively evaluated 213 patients (median age, 71 years) with unresectable locally advanced or metastatic urothelial carcinoma treated with platinum‐based first‐line chemotherapy between May 2003 and April 2021. The patients were categorized into the following two groups: progressive disease (PD) within four cycles (trial ineligible group) and non‐PD within four cycles (trial eligible group). The primary outcomes were the estimated proportion of trial eligible patients for maintenance immunotherapy. The secondary outcomes were the comparison of the overall survival in the trial eligible and ineligible groups and the impact of radiologic response at the second cycle on the fourth cycle. Results Among the 213 patients, 81 (38%) were included in the trial eligible group. The trial eligible group had a significantly longer overall survival than the trial ineligible group (P < 0.001). Of 166 patients who had no PD within two cycles, 85 (51%) patients experienced PD within four cycles. Patients with a complete response or partial response at the second cycle had a significantly lower rate of PD at the fourth cycle (42%) than those with stable disease at the second cycle (59%, P = 0.031). Conclusion We observed 38% of the trial eligible population. Overall survival was significantly different between the trial eligible and ineligible groups.

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Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, with Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients with Bladder Cancer

Cited by 295 publications

References 0 publications

Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy

Advanced urothelial carcinoma: next-generation sequencing reveals diverse genomic alterations and targets of therapy

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer

The impact of eligibility for maintenance immunotherapy on prognosis in patients with unresectable or metastatic urothelial carcinoma

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