Prise en charge du carcinome urothélial

métastatique en 2022
Dr Constance THIBAULT
Hôpital Européen Georges-Pompidou (Paris)
 Essais en 1ère ligne métastatique

X X X

X
Enfortumab Vedotin

Enfortumab Vedotin

cc
 EV-103 Cohorte K : EV +/- pembro en 1ère ligne des carcinomes urothéliaux
métastatiques unfit au cisplatine

Cohort K
Patient Population Dose Escalation Expansion Cohort A
1:1 Randomization
Locally Advanced enfortumab vedotin +
enfortuman enfortuman
enfortumab vedotin
enfortumab
enfortuman vedotin +
or pembrolizumab + pembrolizumab
pembrolizumab
Metastatic
or
Urothelial Cisplatin-ineligible Cisplatin-ineligible
enformab vedotin
enfortumab
Carcinoma 1L 1L
(n=5) (n=40)
Cisplatin-ineligible
(la/mUC)
1L
(n=151)

Rosenberg et al. ESMO 2022

 EV-103 Cohorte K : EV +/- pembro en 1ère ligne des carcinomes urothéliaux
métastatiques unfit au cisplatine

PD-L1 Score
100 High (CPS ≥10)
EV + Pembro EV seul Low (CPS <10)

Tumor size (% Change from Baseline)

80
Not evaluable
Best Overall Response
60
ORR 64% 45% 40
97.1% of assessable patients had tumor reduction
Confirmed CR/PR

Meilleure réponse 20

Complète 10% 4% 0

Partielle 54% 41% -20

Stable 22% 34% -40

Progression 8% 10% -60

PFS (médiane) Non atteinte 8 mois -80

-100
OS (médiane) 22.3 mois 21.7 mois
EV + P (n=69)

Pas de différence selon le statut PD-L1 (CPS)

Rosenberg et al. ESMO 2022

 EV-301 Cohorte K : EV +/- pembro en 1ère ligne des carcinomes urothéliaux
métastatiques unfit au cisplatine

EV+P (N=76) EV Mono (N=73) EV+P EV Mono

TRAEs Any Grades by Preferred Term n (%) n (%) (N=76) (N=73)
≥20% of Patients Any Grade Grade ≥3 Any Grade Grade ≥3 Any Grade Grade ≥3 Any Grade Grade ≥3
Overall 76 (100.0) 48 (63.2) 68 (93.2) 35 (47.9) n (%) n (%) n (%) n (%)
Fatigue 43 (56.6) 7 (9.2) 29 (39.7) 6 (8.2) Skin reactions 51 (67.1) 16 (21.1) 33 (45.2) 6 (8.2)
Peripheral sensory neuropathy 39 (51.3) 1 (1.3) 32 (43.8) 2(2.7)
Peripheral 46 (60.5)
Alopecia 45 (46.1) 0 26 (35.6) 0 2 (2.6) 40 (54.8) 2 (2.7)
neuropathy
Rash masculo-papular 35 (46.1) 13 (17.1) 21 (28.8) 1 (1.4)
Pruritus 30 (39.5) 3 (3.9) 19 (26.0) Ocular disorders 20 (26.3) 0 21 (28.8) 0
1 (1.4)
Dysgeusia 23 (30.3) 0 25 (34.2) 0 Dry eye 18 (23.7) 0 9 (12.3) 0
Weight decreased 23 (30.3) 3 (3.9) 21 (28.8) 1 (1.4) Blurred vision 9 (11.8) 0 10 (13.7) 0
Diarrhea 22 (28.9) 5 (6.6) 20 (27.4) 4 (5.5)
Corneal disorders 0 0 4 (5.5) 0
Decreased appetite 20 (26.3) 0 28 (38.4) 0
Nausea 19 (25.0) 0 25 (34.2) 1 (1.4) Hyperglycemia 11 (14.5) 5 (6.6) 8 (11.0) 7 (9.6)
Dry eye 15 (19.7) 0 8 (11.0) 0 Infusion-related
3 (3.9) 0 4 (5.5) 0
reactions

Rosenberg et al. ESMO 2022

 Prise en charge des carcinomes urothéliaux métastatiques en 2022

1ère ligne JAVELIN-Bladder 100

Eligibles au cisplatine
• Cisplatine + gemcitabine
100 Median Overall Survival (95% CI)
• Dose-dense méthotrexate + mo
90 Avelumab 21.4 (18.9-26.1)
vinblastine + doxorubicine + Control 14.3 (12.9-17.9)
80
cisplatine (ddMVAC) Stratified hazard ratio for death,
0.69 (95% CI, 9.56-0.86)
70 P=0.001

Percent of Patients
60
Inéligibles au cisplatine
50
• Carboplatine + gemcitabine Avelumab
40

Entretien 30 Control

Si RC/RP/SD après CT platine 20

• Avelumab 10

0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38
PD-L1 élevé Months
• Atezolizumab
• Pembrolizumab

Powles et al. NEJM 2019

 Patients traités par cisplatine (n=389) Patients traités par carboplatine (n=269)
100 100
Median OS (95%, CI), months Median OS (95%, CI), months
90 90
Avelumab + BSC 25.3 (18.6, NE) Avelumab + BSC 19.9 (16.0, 24.0)
80 80 BSC alone 12.9 (9.4, 16.2)
BSC alone 16.5 (13.4, 26.8)

Overall survival (%)

70 HR, 0.69 (95% CI: 0.47, 0.91)
Overall survival (%)

70 HR, 0.69 (95% CI: 0.51, 0.94)

60 60

50 50

40 40

30 30

20 20
Avelumab + BSC Avelumab + BSC
10 10 BSC alone
BSC alone

0
0 2 4 6 8 10 12 14 16 18 20 Avelumab en maintenance
22 24 26 28 30 32 34 36 38
0
0 2 4 6 8 10 12 14 16 18
Months
20 22 24 26 28 30 32 34 36 38

Months

chez tous les patients en maladie stable/réponse

No. at risk No. at risk

Avelumab + BSC 183 180 169 157 141 122 103 89 77 66 49 38 32 22 14 8 5 3 2 0 Avelumab + BSC 147 142 130 119 102 88 78 68 59 48 32 21 16 14 9 6 5 1 1 0
BSC 206 199 182 165 142 116 92 76 63 48 42 34 23 17 11 8 9 2 1 0 BSC 122 114 104 91 72 57 52 42 36 29 20 15 13 12 6 3 3 0

après 1L par sels de platine

Patients en réponse partielle (n = 326) Patients avec maladie stable (n=195)
Patients en réponse complète (n = 179)
100 100
100 Median OS (95%, CI), months Median OS (95%, CI), months
Median OS (95%, CI), months 90 90
90 Avelumab + BSC 19.2 (15.4, 24.7) Avelumab + BSC 19.9 (18.2, NE)
Avelumab + BSC NE (20.8, NE) 80 BSC alone 12.1(10.1, 14.3) 80 BSC alone 14.0(10.7, 19.4)
80 BSC alone NE (18.4, NE)

Overall survival (%)

Overall survival (%)

70 HR, 0.62 (95% CI: 0.46, 0.83) 70 HR, 0.70 (95% CI: 0.46, 1.05)
Overall survival (%)

70 HR, 0.81 (95% CI: 0.47, 1.38)

60 60
60
50 50
50
40 40
40
30 30
30

20 20 20
Avelumab + BSC Avelumab + BSC Avelumab + BSC
10 10 BSC alone 10 BSC alone
BSC alone

0 0 0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38

No. at risk Months No. at risk Months Months

No. at risk
Avelumab + BSC 90 90 85 79 70 63 53 41 35 31 24 18 14 13 10 7 3 0 163 161 151 138 123 103 87 77 70 59 45 32 26 18 12 6 6 3 2 0 163 91 82 77 66 60 56 49 40 32 18 15 11 8 4 2 2 2 1 0
Avelumab + BSC Avelumab + BSC
BSC 89 89 86 79 69 57 51 46 38 31 26 22 14 12 6 2 1 0 BSC BSC
163 155 140 115 96 79 60 45 40 30 26 19 16 13 10 8 7 2 1 0 98 91 78 76 63 50 42 34 27 22 16 14 11 8 5 2 1 0

Grivas et al. ESMO 2020

 Données de « vraie vie » (étude AVENANCE)

Figure 2. PFS from start of avelumab treatment Figure 2. PFS from start of avelumab treatment
100 100
Avelumab (N=266)* Avelumab (N=267)
PFS, median (95% CI), mo 5.7 (5.0-7.9) OS, median (95% CI), mo 20.7 (15.2-NE)
90 90

80 80

70 70
66.9%
60 60
PFS, %

PFS, %
50 50

40 40
36.9%
30 30
20
20
10
10
0
0
0 3 6 9 12 15 18 21 24
0 3 6 9 12 15 18 21 24
Months since start of avelumab treatment
No. at risk Months since start of avelumab treatment
(No. of censored patients) No. at risk
266 171 117 92 63 32 12 3 0 (No. of censored patients)
Avelumab 267 250 214 175 116 60 21 6 0
(0) (12) (20) (28) (47) (74) (94) (102) (105) Avelumab (0) (3) (13) (28) (70) (113) (145) (159) (165)
PFS, progression-free survival.
*1 patient has been exclused from this analysis because of an incorrect date of first injection. NE, not estimable; OS, overall survival.

1/3 de patients toujours sous avelumab à 1 an

Barthelemy et al. ESMO 2022
 Long répondeurs (étude JAVELIN Bladder-100)
Table 1. Baseline characteristics
Overall avelumab arm Patients with ≥12 months of
(N=350) avelumab treatment (n=118)

Age, median (range), years 68 (37-90) 69 (43-86)

§ 34% de patients ont reçu l’avelumab ≥ 12 mois Sex, n (%)

Male 266 (76.0) 91 (77.1)
Female 84 (24.0) 27 (22.9)
Pooled geographic region, n (%)
Europe 214 (61.1) 61 (51.7)
North America 12 (3.4) 6 (5.1)

§ Aucun facteur prédictif de longue réponse sous avelumab Asia

Australasia
73 (20.9)
34 (9.7)
32 (27.1)
15 (12.7)
Rest of the world 17 (4.9) 4 (3.4)
ECOG PS, n (%)
0 213 (60.9) 83 (70.3)
1 136 (38.9) 35 (29.7)

§ mOS: non atteinte 2

PD-L1 status, n (%)
1 (0.3) 0

Positive 189 (54.0) 72 (61.0)

Negative 139 (39.7) 39 (33.1)
Unkdown 22 (6.3) 7 (5.9)

§ mPFS (longs répondeurs): 27 mois (IC95% 19-32)

1L chemotherapy regimen, n (%)
Gemcitabine + cisplatin 183 (52.3) 67 (56.8)
Gemcitabine + carboplatin 147 (42.0) 43 (36.4)
Gemcitabine + cisplatin + carboplatin* 20 (5.7) 8 (6.8)
Best response to 1L chemotherapy, n (%)
CR 90 (25.7) 36 (30.5)
PR 163 (46.6) 51 (43.2)
SD 97 (27.7) 31 (26.3)
Site of metastasis at start of chemotherapy, n (%)
Visceral 191 (54.6) 56 (47.5)
Nonvisceral 159 (45.4) 62 (52.5)
Site of primary tumor, n (%)
Upper tract 106 (30.3) 34 (28.8)
Lower tract 244 (69.7) 84 (71.2)

Aragon-Chin et al. ESMO 2022

Prise en charge des carcinomes urothéliaux métastatiques en 2022

1ère ligne 2ème ligne

Eligibles au cisplatine
• Cisplatine + gemcitabine
• Dose-dense méthotrexate +
vinblastine + doxorubicine +
cisplatine (ddMVAC)
Inéligibles au cisplatine
• Carboplatine + gemcitabine
• Pembrolizumab (si naïf IO)
• ADC :
• Enfortumab vedotin
• Sacituzumab (essai)
Altérations de FGFR
• Erdafitinib (ATU, THOR)

Entretien
Si RC/RP/SD après CT platine
• Avelumab

PD-L1 élevé
• Atezolizumab
• Pembrolizumab
 Nouvelles thérapies

Anticorps conjugués Anti-FGFR

Enfortumab Sacituzumab Disitamab Erdafitinib

vedotin govitecan vedotin

Anticorps Anticorps Anticorps

Anti-Nectin 4 Anti-Trop2 Anti-HER2

Cytotoxique Cytotoxique Cytotoxique

MMAE SN-38 MMAE
 Enfortumab Vedotin en 3ème ligne
EV-301 (phase III)

Key eligibility criteria
• Histologically confirmed UC
• Progression or relapse
during or after PD-1/L1
treatment for advanced UC
• Prior platinum-containing
regimen for adavanced UC
• ECOG PS 0 or 1
Enfortumab vedotin
(n = 301)
1,25 mg/kg J1-J8-J15, reprise J28
1:1 randomization
with stratification
Preselected chemotherapy
(n = 307)
Docetaxel 75 mg/m2 or Paclitaxel 175
mg/m2 or Vinflunine 320 mg/m2
Primary endpoint : Overall
survival
Secondary endpoints :
• Progression-free survival
• Disease control rate
• Overall response rate
• Safety

Powles et al. NEJM 2021

 SG médiane Survie sans progression

Enfortumab vedotin 12,88 mois (10,58-15,21) Enfortumab vedotin 5,5 mois (5,32-5,82)
Chimiothérapie 8,97 mois (8,05-10,74) Chimiothérapie 3,71 mois (3,52-3,94)

HR : 0,70 (IC95% : 0,56-0,89), p=0,00142 HR : 0,62 (IC95% : 0,51-0,75) p<0,00001

100 100

Evt/N Evt/N

Survie sans progression (%)

Enfortumab vedotin 134/301 80
Enfortumab vedotin 201/301
80
Chimiothérapie 167/307 Chimiothérapie 231/307
Survie globale (%)

60 60

50 50

40 40

20 20

0 0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

Temps (mois) Temps (mois)

301 286 272 257 246 234 222 190 158 130 105 85 63 52 42 33 23 15 7 4 3 2 1 1 0 301 269 224 208 165 158 102 95 60 56 38 36 23 17 11 7 5 2 2 1 1 0

307 288 274 250 238 219 198 163 131 101 84 66 51 44 32 29 16 11 6 4 2 2 1 0 0 307 259 200 166 116 107 62 57 33 29 18 16 8 8 4 3 2 1 0 0 0 0

Powles et al. NEJM 2021

50
Taux de réponse confirmée; p < 0,001
45 40,6 %
IC95% : 34,9-46,5
40
35
30
25
17,9 %
20 IC95% : 13,7-22,8
15
10
RP=35,8%
5 RP=15,2%
RC=4,9% RC=2,7%
0
Enfortumab vedotin (N=288) Chimiothérapie (N=296)
 Enfortumab Vedotin in Advanced Urothelial Carcinoma
Tolérance
Table 2. Treatment-Related Adverse Events (Safety Population).*

Enfortumab Vedotin Group Chemotherapy Group

Adverse Event (N = 296) (N = 291)
Any Grade Grade ≥3 Any Grade Grade ≥3
number of patients (percent)
Any adverse event 278 (93.9) 152 (51.4) 267 (91.8) 145 (49.8)
Alopecia 134 (45.3) 0 106 (36.4) 0
Peripheral sensory neuropathy† 100 (33.8) 9 (3.0) 62 (21.3) 6 (2.1)
Pruritus 95 (32.1) 4 (1.4) 13 (4.5) 0
Fatigue 92 (31.1) 19 (6.4) 66 (22.7) 13 (4.5)
Decreased appetite 91 (30.7) 9 (3.0) 68 (23.4) 5 (1.7)
Diarrhea 72 (24.3) 10 (3.4) 48 (16.5) 5 (1.7)
Dysgeusia 72 (24.3) 0 21 (7.2) 0
Nausea 67 (22.6) 3 (1.0) 63 (21.6) 4 (1.4)
Maculopapular rash 48 (16.2) 22 (7.4) 5 (1.7) 0
Anemia 34 (11.5) 8 (2.7) 59 (20.3) 22 (7.6)
Decreased neutrophil count 30 (10.1) 18 (6.1) 49 (16.8) 39 (13.4)
Neutropenia 20 (6.8) 14 (4.7) 24 (8.2) 18 (6.2)
Decreased white-cell count 16 (5.4) 4 (1.4) 31 (10.7) 20 (6.9)
Febrile neutropenia 2 (0.7) 2 (0.7) 16 (5.5) 16 (5.5)

* The safety population included all patients who received any amount of trial drug. Included are treatment-related ad-
verse events that occurred in at least 20% of patients in either treatment group or treatment-related adverse events of
grade 3 or higher that occurred in at least 5% of patients in either treatment group. Treatment-related adverse events
are those for which there is a reasonable possibility that they were caused by the trial treatment, as assessed by the in-
vestigator. If data regarding the relationship to treatment were missing, the event was considered to be related to treat-
ment.
† A total of 113 patients (55 in the enfortumab vedotin group and 58 in the chemotherapy group) had preexisting periph-
eral neuropathy.
 Toxicités spécifiques de l’Enfortumab Vedotin

Réactions cutanées Neuropathie périphérique Affections oculaires

Réactions liées à la perfusion Hyperglycémie

 Toxicités spécifiques de l’Enfortumab Vedotin

0,4 mois (~13 jours), n=139*

Réactions cutanées
0,7 mois (~20 jours), n=46

2,7 mois (~82 jours), n=137

Neuropathie périphérique†
0,8 mois (~25 jours), n=89

4,4 mois (~132 jours), n=2

Troubles cornéens
NA (NA)

1,9 mois (~58 jours), n=47

Sécheresse oculaire
2,5 mois (~75 jours), n=9
Médiane : Plage :
2,5 mois (~74 jours), n=12 Enfortumab vedotin
Vision trouble Chimiothérapie
0,9 mois (~26 jours), n=6

0,5 mois (~15 jours), n=26

Réactions liées à la perfusion
0,03 mois (~1 jour), n=13

0,6 mois (~17 jours), n=19

Hyperglycémie
1,4 mois (~43 jours), n=1
0 1 2 3 4 5 6 7 8 9 10 11 12

Délai d'apparition (mois)

 Cas décrits d’atteinte cutanée avec
décès toxiques
- Toxidermie
- Syndrome Stevens Johnson/Lyell
à Atteinte des plis
à Décollements cutanés

SUSPENSION de déc 2021 à juillet 2022

de l’accès compassionnel et des inclusions
dans plusieurs études en cours

Guerrois et al. EJC 2022

 Sacituzumab govitecan
TROPHY-U01 (phase II)

Loriot et al. ESMO 2022

 TROPHY-U01: efficacité

Cohort 1
Critère de jugement
(N = 113)

Taux de réponse objective [95% CI] 27% [19, 37]

Réponse complète, n (%) 6 (5)
Réponse partielle, n (%) 25 (22)

Patients
5,9
Durée médiane de réponse, mois (intervalle) [4,70 ; 8,60]
(1,4 – 11,7)
Discontinued without event

1,6 Ongoing response

Délai median de réponse, mois (intervalle) (1,2 – 5,5)

Onset of response
PD or death
Partiel response
Complete response

Survie sans progression : 5,4 mois (3,5 ; 6,9) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Months
Survie globale : 10,5 mois (8,2 – 12,3)

Loriot et al. ESMO 2020

 TROPICS-04 : phase III (post platine, post IO)

Study Population Sacituzumab

Govitecan
advanced
Locally asvanced
unresectable or mUC Endpoints
10 mg/kg D1 & D8
of 21-D cycle Primary
Upper/lower tract
tumors
OS
Continue treatment until
Mixed histologic loss of clinical benefit or
types are allowed if Secondary
urothelial unacceptable toxicity
is predominant Treatment of ORR, PFS, DOR and
N=600 CBR by
Physician Choice
Progression after 1:1 PI assessment
PLT-based and CPI Docetaxel 75 mg/m2 and BICR using
therapy RECIST V1.1ª
Treatment beyond PD
OR may be permitted in
OR EORTC QLQ-C30
patient deemed to be Score and
Paclitaxel 175 mg/m2 receiving clinocal benefit
Cisplatin only in EuroQOL
per investigator EQ-5D-5L QOL Score
(neo)adjuvant setting OR assessment
in progression within
12 months and Safety and tolerability
Vinflunine 320 mg/m2
subsequent CPI in on D1 of 21 -D cycle
metastatic setting
 RC48-ADC (Disitamab Vedotin)
Tumeurs HER2 positives (IHC 2+ ou 3+)

N=101 pré-traités
2/3 avaient reçu ≥ 2 lignes ORR 50%
Characteristics Total (N=107)
Age (years)
Median 63
Mean (SD) 61.8 (8.13)
Gender
Male (n,%) 80 (74.8)
ECOG
0 40 (37.4%)
1 66 (61.7%)
2 1 (0.9%)
HER2 status
IHC3+ or IHC2+FISH+ (n,%) 45 (42.1%)
IHC2+ FISH- (n,%) 53 (49.5%)
IHC2+FISH unknown (n,%) 9 (8.4%)
Primary Lesion
Bladder (n,%) 55 (51.4%) Analyse en sous-groupe cORR
Renal pelvis (n,%) 28 (26.2%)
Ureter (n,%) 30 (28.0%) Subgroups cORR (%, 95 CI)
metastasis IHC2+FISH+ or IHC3+ (n=45) 62.2% (46.5%, 76.2%)
Lung (n,%) 53 (49.5)
Liver (n,%) 48 (44.9%) IHC2+FISH- (n=53) 39.6% (26.5%, 54.0%)
Priori chemotherapy Visceral Metastasis (n=97) 51.5% (41.2%, 61.8%)
1 Line (n,%) 38 (35.5%)
≥ 2 Lines (n,%) 69 (64.5)
Metastasis to Liver (n=48) 52.1% ‘37.2%, 66.7%)
Prior PD-1/PD-L1 therapy (n,%) 27 (25.2%) Post PD1/PDL1 Treatments (n=27) 55.6% (35.3%, 74.5%)
Post 1 line of Chemotherapy (n=38) 50.0% (33.4%, 66.6%)
Post ≥ 2 Lines of Chemotherapy (n=69) 50.7% (38.4%, 63.0%)

Sheng et al. Abstract 4520 ASCO 2022

 Disitamab + pembrolizumab

Phase III randomisée (SGNDV-001)

Pembrolizumab + Disitamab
Critères d’inclusion:
- 1ère ligne de traitement métastatique R
- Carcinome urothélial HER+ (IHC 1/2/3)
Chimiothérapie

≃ 2/3 des patients

 Anti-FGFR Non-invasive bladder cancer
Mutations ~ 70% tumors

Gastric cancer Invasive bladder cancer

Amplification ~5% tumors Mutations/translocation ~15%
Endometrial cancer Upper tract urothelial
FGFR2 FGFR3 Mutations/translocation ~35%
Mutations ~15%
18 ligands
Multiple myeloma
Translocation ~20% tumors

P P
P P

P
FGFR4

P
FGFR1

P
Proliferation/migration/
Breast cancer anti-apoptosis/angiogenesis Colorectal and
Amplification ~10% ER +ve hepatocellular cancer
Squamous NSCLC Prostate (FGFR1 and 4) Up-regulated FGF19
Amplification ~20% Up-regulated FGFR4 and FGF ligands
 Essai BLC2001 (erdafitinib)

200
ORR (Primary Endpoint): 40%
Maximal Reduction From Baseline

100 PD: 18%

FGFR mutation
50 FGFR fusion

-50

-100
Patient

Siefker-Radtke. ASCO 2018. Abstr 4503. Loriot. NEJM. 2019;381:338.

Table 3. Adverse Event inthe 99 Patients in the Selected-Regimen Group.*
Adverse Event Any Grade Grade 1 Grade 2 Grade ≥3
number of patients (percent)
Hyperphisphatemia
Hyperphosphatemia 76 (77) 53 (54) 21 (21) 2 (2)
Stomatitis 57 (58) 21 (21) 26 (26) 10 (10)
Diarrhea 50 (51) 31 (31) 15 (15) 4 (4)
Dry mouth 45 (46) 34 (34) 11 (11) 0
Decreased appetite 38 (38) 18 (18) 20 (20) 0
Dysgeusia 37 (37) 23 (23) 13 (13) 1 (1)
Fatigua 32 (32) 12 (12) 18 (18) 2 (2)
Dry skin 32 (32) 24 (24) 8 (8) 0
Alopecia 29 (29) 23 (23) 6 (6) 0
Constipation 28 (28) 19 (19) 8 (8) 1 (1)
Hand-foot syndrome 23 (23) 6 (6) 12 (12) 5 (5)
Anemia 20 (20) 9 (9) 7 (7) 4 (4)
Asthenia 20 (20) 2 (2) 11 (11) 7 (7)
Nausea 20 (20) 13 (13) 6 (6) 1 (1)
Dry eye 19 (19) 14 (14) 4 (4) 1 (1)
Onycholysis 18 (18) 6 (6) 10 (10) 2 (2)
Alanine aminotransferase in- 17 (17) 13 (13) 2 (2) 2 (2)
creased
Paronychia 17 (17) 3 (3) 11 (11) 3 (3)
Blurred vision 17 (17) 10 (10) 7 (7) 0
Erdafitinib chez les patients avec un carcinome urothélial métastatique pré-
traités (étude THOR)

Erdafitinib starting at 8 mg/day PO

Cohort 1 QD in 21-d cycles
Prior anti–PD-(L)1,
Adults with surgically
≤2 prior lines of
unresectable or
systemic tx Investigator’s choice of treatment*
metastatic UC; meet
Until PD, intolerable
molecular eligibility
toxicity, consent
criteria for FGFR
withdrawal, or
alteration status per
Erdafitinib starting at 8 mg/day PO investigator decision
FGFRi Clinical Trial
Cohort 2 QD in 21-d cycles
Assay; ECOG PS 0-2
No prior anti–PD-(L)1,
(N = 631)
1 prior line of
NCT03390504 systemic tx Pembrolizumab 200 mg IV Q3W *Vinflunine 320 mg/m2 IV or
docetaxel 75 mg/m2 IV Q3W.
§ Primary endpoint : OS
§ Secondary endpoints : PFS, ORR, DoR, PROs, safety
Slide credit: clinicaloptions.com
 Screening FGFR (mutation ET translocation) ++++

FGFR + FGFR wt

Eligible à essai THOR ?

Traitement standard

Inclusion THOR ATU (erdafitinib)

Prise en charge des carcinomes urothéliaux métastatiques en 2022

1ère ligne 2ème ligne 3ème ligne

Eligibles au cisplatine
• Cisplatine + gemcitabine
• Dose-dense méthotrexate +
vinblastine + doxorubicine +
cisplatine (ddMVAC)
Inéligibles au cisplatine
• Carboplatine + gemcitabine
Entretien
Si RC/RP/SD après CT platine
• Avelumab
• Pembrolizumab (si naïf IO)
• Enfortumab vedotin (ATU)
• Essais cliniques:
• Sacituzumab
govitecan
(TROPICS-04)
Altérations de FGFR
• Erdafitinib (ATU, THOR)
• Enfortumab vedotin (ATU)
• Taxanes
• Essais cliniques:
• Sacituzumab
Altérations de FGFR
• Erdafitinib (ATU, THOR)

PD-L1 élevé
• Atezolizumab
• Pembrolizumab