This study aims to prospectively observe whether certain alterations in some genes related to the DNA repair mechanism are related to better response to platinum-based chemotherapy used to treat metastatic bladder or urothelial cancers.
Informed consent obtained before any study-specific procedures. Patients must be able to understand and be willing to sign a written informed consent.
Male or female patient ≥18 years of age.
Histological or cytological documentation of urothelial cancer.
Available tumor tissue for analysis
Previous treatment for metastatic or locally advanced disease.
Previous adjuvant therapy within 1 year from the diagnosis of metastatic disease.
Prior treatment with immunotherapy.
Previous or concurrent cancer that is distinct in primary site or histology from urothelial cancer within 3 years before enrollment EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ], and T1 [tumor invades lamina propria]), pT2 prostate cancer with PSA<0.01.
Parallel
Platinum + Gemcitabine
DrugEligible patients will be treated with platinum-based chemotherapy (i.e. cisplatin + gemcitabine or carboplatin + gemcitabine).
Avelumab first-line maintenance
DrugPatients with stable disease or tumor response after treatment with platinum-based chemotherapy will start treatment with avelumab 800 mg fat dose Q2 weeks until progression of disease or unacceptable toxicity
NGS test for DDR alterations
Diagnostic testAll patients will be tested for DDR alterations on tumor tissue.
Overall Response Rate (ORR) by DDR group.
The difference in ORR defined as the percentage of patients who achieve PR or CR as measured by RECIST 1.1, to the platinum-based chemotherapy between patients with metastatic or locally advanced urothelial cancer with or without DDR genes alterations.
Progression Free Survival (PFS) by DDR group.
The PFS defined as the time elapsed from start of investigational treatment to the documentation of investigator-assessed disease progression, according to RECIST 1.1 \[22\], or death due to any cause, whichever occurs first in patients with or without DDR genes alterations.
Overall Survival (OS) by DDR group.
The OS is defined as time elapsed from start of treatment to the date of death due to any cause in patients with or without DDR genes alterations.
Overall Response Rate (ORR) by treatment group.
The ORR is defined as the percentage of patients who achieve PR or CR as measured by RECIST 1.1 criteria in patients with or without DDR genes alterations between those treated with carboplatin o cisplatin.
Disease Control Rate (DCR) by treatment group.
The disease control rate (DCR) is defined as the percentage of patients who achieve stable disease (SD), or PR or CR as measured by RECIST 1.1 criteria in patients treated with carboplatin o cisplatin.
Expression of PDL1
This is the description of the rate of patients with positive expression of the marker over the study population.
Expression of Nectin-4
This is the description of the rate of patients with positive expression of the marker over the study population.
Expression of Trop-2
This is the description of the rate of patients with positive expression of the marker over the study population.
Expression of Her-2
This is the description of the rate of patients with positive expression of the marker over the study population.
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