S1314, Co-expression Extrapolation (COXEN) Program to Predict Chemotherapy Response in Patients With Bladder Cancer

The proportion of participants achieving pT0 in both favorable and unfavorable treatment specific-COXEN score categories.

Unit of measure is the number of participants in each category that achieved pT0

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The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores

This will be done in two ways:

• By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. .
• By evaluating the correlation between the GC- and the DDMVAC-COXEN score.

The proportion of participants achieving <=pT1 in both favorable and unfavorable treatment specific-COXEN score categories.

Unit of measure is the number of participants in each category that achieved <= pT1

____________________________________________________________________________________________________________________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores

This will be done in two ways:

• By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. .
• By evaluating the correlation between the GC- and the DDMVAC-COXEN score.

To assess in a hypothesis generating fashion, the ability of COXEN to select for an individual chemotherapy regimen (GC vs DDMVAC)

P-values are reported as a measure of whether COXEN can select between GC/DDMVAC and to determine the significance of interactions between treatment specific COXEN scores and treatment arms in models predicting either pT0 or <= pT1. Interactions with p-values > 0.05 are interpreted as not significant.

________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores

This will be done in two ways:

• By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. .
• By evaluating the correlation between the GC- and the DDMVAC-COXEN score.

The Pearson and Spearman correlation coefficients for GC-and ddMVAC-COXEN score were calculated and are reported below.

___________________________________________________________________________________________________________________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores

This will be done in two ways:

• By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. .
• By evaluating the correlation between the GC- and the DDMVAC-COXEN score.

In addition to stratification factors and dichotomous COXEN GEM score, an indicator for treatment arm and the interaction of treatment arm with COXEN GEM score was also included in a logistic regression model. A significant interaction would suggest that the respective COXEN GEM score was able to differentiate whether a patient was more likely to respond to one chemotherapy regimen over another. *note that this is the same objective at Primary Outcome #3 above - this was erroneously listed twice in the protocol.

5-year OS curve was estimated using the Kaplan-Meier method. Included all COXEN evaluable participants regardless of arm assignment. The report groups were favorable vs. unfavorable COXEN status.

Pathologic complete response rate at the time of cystectomy following GC or DDMVAC treatment

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. Grade 3 is less severe than Grade 5.

Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL* (bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden).

Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related to AE

*ADL- Activities of Daily Living