First-line systemic treatments for bladder cancer are based on a combination of cytotoxic and immunotherapy, sequentially or concomitantly. Immune checkpoint inhibition (ICPI) is a powerful treatment for patients with metastatic urothelial carcinoma (UC). Since 2017, pembrolizumab (anti-PD1) can be offered as a second-line treatment after failure of platinum agents. In patients responding to platinum salts in first-line treatment, it is possible to maintain efficacy with maintenance treatment with another ICPI, avelumab (anti-PDL1). The phase III JAVELIN BLADDER 100 study compared avelumab to supportive care alone after successful platinum-based chemotherapy. At 30 months, 19.3% of patients were still in response compared to only 6.3% in the supportive care arm. However, biomarker analysis on tumor tissue did not show a robust signature on an individual scale. Recently, two phase 3 trials in first-line were presented at the ESMO 2023 congress. The first, in patients who could receive cisplatin-based chemotherapy, found a benefit on overall survival of adding Nivolumab in combination and then maintaining it for two years. The second proposed combined Enfortumab Vedotin and Pembrolizumab versus standard chemotherapy, with an overall survival for the study arm of more than 31 months. These trials confirm the essential role of immunotherapy in urothelial carcinomas. This progress is tempered by toxicity, cost and the lack of data on patient selection and treatment sequence. Although "prognostic" biomarkers have been identified, they cannot guide the choice of therapy, but only predict the expected outcomes, regardless of the treatment; biomarkers capable of predicting clinical benefit ("predictive") are urgently needed. It is therefore essential to identify a predictive signature at the individual level. The study authors have validated an in vitro model of heterotypic spheroids (SPHERTEST) composed of commercial urothelial carcinoma tumor cells and PBMCs from healthy donors. The aim of the study is to validate this model with PBMCs from UC patients to evaluate the effects of immunotherapy on the immune response and on tumor cell survival in vitro. The study hypothesis is that the outcome of the pre-therapeutic test based on a heterotypic spheroid model with PBMC from patients with advanced or metastatic urothelial carcinoma (SPHERTEST) is related to the response to checkpoint inhibitor (CI) treatment.
Study Type
OBSERVATIONAL
Enrollment
32
The SPHERETEST is an in vitro model of heterotypic spheroids composed of commercial urothelial carcinoma tumor cells and leukocyte mononuclear cells from healthy donors.
Institut du Cancer de Montpellier
Montpellier, France
NOT_YET_RECRUITINGInstitut Régional du Cancer de Montpellier
Montpellier, France
NOT_YET_RECRUITINGCentre Antoine Lacassagne
Nice, France
NOT_YET_RECRUITINGCHU de Nimes
Nîmes, France
RECRUITINGIuct Oncopole
Toulouse, France
RECRUITINGSPHERTEST measurement of potential therapeutic efficacy
Yes/No. Differential in spheroid size before and after treatment according to the formula: R=M1-M0. R = test results, M0 = average spheroid size without immunotherapy treatment, M1 = average spheroid size with immunotherapy treatment. When R is ≤ 0, SPHERTEST = "yes" or "potential therapeutic efficacy". When R is \> 0, SPHERTEST = "no" or "absence of potential therapeutic efficacy"
Time frame: Day 0
Progression-free survival
Yes/No according to RECIST criteria
Time frame: Month 12
Histology of cells
Pure transitional cells vs predominantly transitional cells
Time frame: Inclusion
Presence of an aggressive minority component
Yes/no
Time frame: Inclusion
Type of other component
Micropapillary, microcystic, trophoblastic differentiation, epidermoid differentiation, nested, plasmacytoid, sarcomatoid, rhabdoid, lymphoepitheliomatoid, large cell, undifferentiated or neuroendocrine
Time frame: Inclusion
Tumor grade
WHO grading
Time frame: Inclusion
PD1/PDL1 status
Yes/no
Time frame: Inclusion
PDL1 score
positive/negative
Time frame: Inclusion
Type of metastatic involvement
Locally advanced (= local recurrence, or pelvic lymph node involvement) or Metastatic sites: liver, bone, lung, brain, extrapelvic lymph node, other
Time frame: Inclusion
Primary tumor site
Bladder/Urethra/upper urinary tract/Urethra
Time frame: Inclusion
Hemoglobin level
g/dL
Time frame: Inclusion
Hemoglobin level
g/dL
Time frame: Cycle 2 visit
Lactate dehydrogenase level
UI/L
Time frame: Inclusion
Lactate dehydrogenase level
UI/L
Time frame: Cycle 2 visit
C-reactive protein level
mg/L
Time frame: Inclusion
C-reactive protein level
mg/L
Time frame: Cycle 2 visit
Neutrophil count
G/L
Time frame: Inclusion
Neutrophil count
G/L
Time frame: Cycle 2 visit (cycles are spaced 3 weeks (pembrolizumab) or 2 weeks (avelumab) apart)
Lymphocyte count
G/L
Time frame: Inclusion
Lymphocyte count
G/L
Time frame: Cycle 2 visit (cycles are spaced 3 weeks (pembrolizumab) or 2 weeks (avelumab) apart)
Number of lines of systemic treatment received in the metastatic phase
0, 1, 2, ≥3
Time frame: Inclusion
Type of platinum salt received prior to immunotherapy
Cisplatin or carboplatin
Time frame: Inclusion
Treatment regimen prior to anti-PD1 therapy
Neoadjuvant with progression within 12 months / Adjuvant with progression within 12 months / Initially locally advanced/metastatic
Time frame: Inclusion
Current treatment: whether treatment is combined with another molecule
Cisplatin / entoftumab-vedotin
Time frame: Inclusion
Antibiotics in the previous month
Duration (days)
Time frame: Inclusion
Corticosteroid therapy > 10 mg prednisolone equivalent at immunotherapy initiation
Yes/no
Time frame: Inclusion
Taking an immunosuppressant other than corticosteroid therapy at immunotherapy initiation
Yes/no
Time frame: Inclusion
Any comedication at immunotherapy initiation
Protein pump inhibitors / beta blockers / metformin / statin
Time frame: Inclusion
Patient functioning level
ECOG Performance Status Scale (1-5)
Time frame: Inclusion
BCG vaccine
Yes/no
Time frame: Inclusion
Mitomycin therapy
Yes/no
Time frame: Inclusion
History of auto-immune disease
Yes/no
Time frame: Inclusion
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