Daniel Castellano Oncología Médica. Unidad de Tumores GenitoUrinarios Hospital Universitario 12 de Octubre I + 12 Research Institute @H120_GUCancer @cdanicas Cáncer de Vejiga avanzado: presente y futuro
Daniel Castellano
Oncología Médica. Unidad de Tumores GenitoUrinariosHospital Universitario 12 de Octubre
I + 12 Research Institute@H120_GUCancer
@cdanicas
Cáncer de Vejiga avanzado: presente y futuro
Concepto de paciente ineligible a tratamiento basado en cisplatino
50% de pacientes 15-20% de pacientes
Durable Responses With Cisplatin-Based but not Carboplatin CT in advanced UC
Cisplatin Eligible Cisplatin Ineligible
Gemcitabine + Cisplatin[1,2]
ORR: 49%CR: 12%Median OS: 14.0 mos
Dose Dense MVAC[3]
ORR: 72%CR: 25%Median OS: 15.1 mos
Gemcitabine + Carboplatin[4]
ORR: 36%CR: 3%Median OS: 9.3 mos
1. von der Maase H, et al. J Clin Oncol. 2005;23:4602-4608. 2. von der Maase H, et al. J Clin Oncol. 2000;18:3068-3077. 3. Sternberg CN, et al. Eur J Cancer. 2006;42:50-54. 4. De Santis M, et al. J Clin Oncol. 2012;30:191-199.
Prop
ortio
n Su
rviv
ing 1.0
0.80.60.40.2
00 12 24 36 48 60 72 84
MosPatients at Risk, n
203202
118125
5062
3640
3034
2329
79
01
GCMVAC
GC: median 14.0 mos (12.3-15.5 mos)MVAC: median 15.2 mos (13.2-17.3 mos)HR: 1.09 (0.88-1.34)Log-rank P = .44, Walds P = .66
GCMVAC
10080604020
00 2 4 6 8 10 12
YrsPatients at Risk, nN
129134
3245
1529
1123
48
20
Median5 yrs, %(95% CI)
M-VACHD M-VAC
O112101
M-VACHD M-VAC
HD M-VAC15.1 mos
21.8 (14.5-21.9)
M-VAC14.9 mos
13.5 (7.4-19.6)
Log-rank P = .042HR: 0.76 (95% CI: 0.58- 0.99)
100
80
6040
200
0 1 2 3 4 5 6Yrs
Patients at Risk, nN119119
3744
1315
75
32
12
M-CAVIGC
O108110
Surv
ival
(%)
7
Log-rank test P = .64
M-CAVIGC
11
First-line randomised trials in cisplatin-based (fit) advanced urothelial carcinoma
Better patient selection, earlier diagnosis and screening, better supportive care (growth factors)
Author Treatment N RR (%) OS (months) Best arm
Loehrer MVACCDDP
126120
3912
12.58.2
MVAC > CDPP
Logothetis MVACCISCA
6555
6546
12.610.0
MVAC > CISCA
Von der Maase MVACGC
202203
4649
14.813.8
MVAC ~ GC
Sternberg HD-MVAC+ G-CSFMVAC
134129
6250
14.514.1
HD-MVAC ≥ MVAC
Bamias MVAC+ GCSF
DC + GCSF
109111
5437
14.29.3
MVAC > DC
Dreicer MVACPC
4441
3628
15.413.8
MVAC > PC
Bellmunt PCGGC
312315
57.146.4
15.712.8
PCG ~ GC
Bellmunt et al. Ann Oncol 2014;25 Suppl 3:iii40–8
Patients with poor comorbid status or impaired renal function ‘unfit’
Management of metastatic disease
PS ≤2 plus poor renal function
Carboplatin-based regimens or single-agents: taxane, gemcitabine
Cisplatin-based combination chemotherapy
(e.g. MVAC, GC, HDMVAC, PCG)
Clinical trial
Best supportive careProgression <12 months
Second-line chemotherapy1.Vinflunine2.Taxane-based3.Clinical trial
Progression >12 months1. Platinum-based rechallenge
First line• FIT → CISPLATIN-based combination• UNFIT → CARBOPLATIN-based regimen
Subsequent lines• Vinflunine• Taxane-based • Platinum rechallenge
Evolución de la terapia sistémica para cáncer urotelial
BLA, Biologics License Applicationhttp://www.accessdata.fda.gaov/scripts/cder/drugsatfda/index.cfm; http://www.ema.europa.eu/ema/1. Sternberg et al. Cancer 1989;64:2448–58; 2. McCaffrey et al. J Clin Oncol 1997;15:1853–73. von der Maase et al. J Clin Oncol 2005;23:4602–8; 4. Sternberg et al. J Clin Oncol 2001;19:2638–465. Vaughn et al. J Clin Oncol 2002;20:937–40; 6. Bellmunt et al. J Clin Oncol 2009;27:4454–617. Rosenberg et al. Lancet 2016;387:1909–20; 8. Balar et al. Lancet 2017;389:67–769. Sharma et al. Lancet Oncol 2017; doi: 10.1016/S1470-2045(17)30065-710. Bellmunt et al. N Engl J Med 2017; doi: 10.1056/NEJMoa161368311. Balar et al. J Clin Oncol 2017;35(suppl 6S):Abstract 284
FDA-Approved Checkpoint Inhibitors for UC
1. Atezolizumab [package insert]. July 2018. 2. Avelumab [package insert]. October 2017. 3. Durvalumab [package insert]. February 2018. 4. Nivolumab [package insert]. July 2018. 5. Pembrolizumab [package insert]. June 2018.
Agent Target Schedule FDA Approval Type by SettingPost-Platinum Frontline Cisplatin Ineligible
Atezolizumab[1] PD-L1 Q3W Level 1 AcceleratedAvelumab[2] PD-L1 Q2W Accelerated --Durvalumab[3] PD-L1 Q2W Accelerated --Nivolumab[4] PD-1 Q4W Accelerated --Pembrolizumab[5] PD-1 Q3W Level 1 Accelerated
Currently Approved Immunotherapy After Platinum-based Chemotherapy
Progression
KEYNOTE-045: Pembrolizumab vs Chemotherapy in Postplatinum Metastatic UC§ Randomized phase III trial
Pembrolizumab200 mg Q3W
(N = 270)
Investigator’s ChoicePaclitaxel 175 mg/m2 Q3W orDocetaxel 75 mg/m2 Q3W orVinflunine 320 mg/m2 Q3W
(N = 272)
Bellmunt J, et al. N Engl J Med. 2017;376:1015-1026.
Treated up to 24 mos or until CR, PD,
unacceptable AE, or investigator decision*†
Treated until PD, unacceptable AE, or patient withdrawal of
consent
*Select patients allowed to continue treatment beyond initial radiographic progression. †Patients who achieved CR could discontinue treatment after 24 wks and at least 2 doses after initial CR.
§ Primary endpoints: OS, PFS in overall and in PD-L1 CPS ≥ 10% populations
§ Secondary endpoints: ORR, DoR in overall and in PD-L1 CPS ≥ 10% populations; safety
Patients with metastatic or locally advanced UC after recurrence or
progression following platinum-based chemotherapy;
ECOG PS ≤ 2; evaluable tumor tissue for PD-L1 testing
(N = 542)
Data cutoff: May 19, 2017
KEYNOTE-045: Overall Survival
270 194 147 116 98 67 23272 171 109 73 58 35 13
44.4%30.3% 33.2%
19.7%
0 4 8 12 16 20 24 28 320
20
40
60
80O
S (%
)
Mos
100
de Wit, et al. ESMO 2017. Abstract LBA37_PR.
HR: 0.70 (95% CI: 0.57-0.86; P = .0003)
Pembro(n = 270)
CT(n = 272)
Median OS, mos (95% CI)
10.3 (8.0-12.3)
7.4 (6.3-8.3)
PembroCT
Patients at Risk, n
IMvigor211: Atezolizumab vs Chemotherapy for Postplatinum Advanced UC§ Open-label, 2-arm, randomized phase III trial
Atezolizumab1200 mg Q3W
Investigator’s ChoicePaclitaxel 175 mg/m2 Q3W orDocetaxel 75 mg/m2 Q3W orVinflunine 320 mg/m2 Q3W
Powles T, et al. Lancet. 2018;391:748-757.
Treated until loss of clinical benefit,
unacceptable AE, or investigator decision
Treated until RECIST v1.1 PD or unacceptable AE
§ Primary endpoints: OS
§ Secondary endpoints: ORR, PFS, safety, pharmacokinetics
Patients with metastatic or locally advanced UC after recurrence or progression following platinum-
based chemotherapy; ECOG PS 0/1; evaluable tumor
tissue for PD-L1 testing(N = 932)
Median OS, Mos (95% CI)
11.1 (8.6-15.5)10.6 (8.4-12.2)
IMvigor211: OS in PD-L1–Positive (IC2/3) Patients
Powles T, et al. Lancet. 2018;391:748-757.
AtezolizumabChemotherapy
Events/Patients, n
72/11688/118
12-Mo OS Rate, % (95% CI)
46.4 (37.3-55.6)41.2 (32.2-50.3)
Stratified HR: 0.87 (95% CI: 0.63-1.21; P = .41)
100
80
60
40
20
0
OS
(%)
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 25Patients at Risk, n
AtezolizumabChemotherapy
116118
112109
100100
8895
8591
8285
7782
7375
7171
6365
5861
5551
5147
4741
3932
3528
2724
2318
1915
1511
119
67
65
12
-1
--
Mos
Post Platinum: Phase II StudiesDurvalumabNivolumabAvelumab
Phase II Studies of Immune Checkpoint Inhibitors Leading to Accelerated Approval
Nivolumab[1]
Durvalumab[3]Avelumab[2]
OS
(%)
100
80
60
40
20
00 3 6 9 12 15
Patients at Risk, n(number censored)All treated patients 265 (0) 198 (3) 148 (4) 63 (71) 5 (125) 0 (130)
All treated patients (n = 265)
Median OS: 8.74 mos(95% CI: 6.05 to not reached)
100
80
60
40
20
0
OS
(%)
0 3 6 9 12 151 2 4 5 7 8 1011 1413 161718Mos Since Treatment Initiation
Patients at Risk, n 44 43 40 31 30 28 25 25 25 23 22 21 19 17 14 10 6 2 0
Median OS: 13.7 mos (95% CI: 8.5-NE)
Prob
abili
ty o
f OS
1.0
0.8
0.6
0.4
0.2
00 3 6 9 12 15 18 21 24 27
Mos From First Dose
Total
Median OS, mos (95% CI)
18.2 (8.1-NE)
12-mo OS rate, % (95% CI) 55 (44-65)
Total (n = 191)
1. Sharma P, et al. Lancet Oncol. 2017;18:312-322. 2. Apolo AB, et al. J Clin Oncol. 2017;35:2117-2124. 3. Powles T, et al. JAMA Oncol. 2017;3:e172411.
Overall population (n = 44)
Clinical outcomes according to PD-L1 status and age in the prospective international SAUL study of atezolizumab for locally
advanced or metastatic urothelial carcinoma or non-urothelial carcinoma of the urinary tract
Cora N. Sternberg1, Axel S. Merseburger2, Ernest Choy3, Daniel Castellano4, Fernando Lopez-Rios5, Nick James6, Giuseppe L. Banna7, Ugo De Giorgi8, Cristina Masini9, Aristotelis Bamias10, Xavier Garcia del Muro11, Thomas Powles12, Ignacio Duran13, Craig Gedye14, Marija Gamulin15, Friedemann Zengerling16, Lajos Geczi17, Sabine de Ducla18, Simon Fear18, Yohann Loriot19
1San Camillo and Forlanini Hospitals, Rome, Italya; 2Department of Urology, Campus Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany; 3CREATE Centre, Section of Rheumatology, Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK; 4Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain; 5Hospital Universitario HM Sanchinarro, Madrid, Spain; 6Institute of Cancer and Genomic Services, University of Birmingham, and Cancer Centre, Queen Elizabeth Hospital, Birmingham, UK;7Cannizzaro Hospital, Catania, Italy; 8Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 9Medical Oncology Unit, AUSL-IRCCS Reggio Emilia, Reggio Emilia, Italy; 10National and Kapodistrian University of Athens, Alexandra Hospital, Athens, Greece; 11Institut Catala d’Oncologia, IDIBELL, Barcelona, Spain; 12Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew’s Hospital, London, UK; 13Hospital Universitario Virgen del Rocio, Seville, Spainb; 14Calvary Mater Newcastle, Waratah, NSW, Australia; 15University Hospital Centre ‘Zagreb’, Zagreb, Croatia; 16Department of Urology, University Hospital Ulm, Ulm, Germany; 17National Institute of Oncology, Budapest, Hungary; 18F. Hoffmann-La Roche Ltd, Basel, Switzerland; 19Department of Cancer Medicine and INSERM U981, Université Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, FranceaCurrent affiliation: Weill Cornell Medicine, New York, NY, USA. bCurrent affiliation: Hospital Universitario Marques de Valdecilla. Santander, Spain
D Castellano, e-poster 2019
Figure 1. OS according to PD-L1 status
0 3 6 9 12 15 18 21Time (months)
Estim
ated
sur
viva
l (%
)
100
75
50
25
0
IC 2/3 (n=268)IC 0/1 (n=666)
OS IC 0/1 (n=666)
IC 2/3 (n=268)
No. of deaths, n (%) 388 (58) 132 (49)
Median OS, months (95% CI) 7.9 (6.8–9.1)
11.6 (8.8–18.8)
6-month OS rate, % (95% CI) 57 (53–61) 67 (61–72)12-month OS rate, % (95% CI) 38 (34–42) 48 (42–55)
Figure 2. Median OS and PFS within PD-L1 subgroups
0 2 4 6 8 10 12 14 16 18 20
IC 2/3 and 0 prior metastatic lines (n=111)
IC 0/1 and 0 prior metastatic lines (n=246)
3 prior lines (n=20)
2 prior lines (n=52)
1 prior line (n=548)
0 prior lines (n=384)
IC 2/3 IMvigor211-like (n=176)
IC 0/1 IMvigor211-like (n=427)
IC 2/3 (n=268)
IC 0/1 (n=666)
All patients (n=1004)
Median PFS Median OS
Months
Summary: PD-L1 Pathway Inhibitors as Postplatinum Therapy
Overall Response: Urothelial Carcinoma Post Platinum
Historical control with CT ~ 10%
Atezolizumab[1]
IMvigor 211 Avelumab[2] Durvalumab[3]
ENRICHEDNivolumab[4]
Checkmate 275Pembrolizumab[5]
KEYNOTE 045
70
60
50
40
30
20
10
0
13.4%
18.2%17.8% 19.6% 21.1%
Patie
nts
(%)
1. Powles T, et al. Lancet. 2018;391:748-757. 2. Apolo AB, et al. J Clin Oncol. 2017;35:2117-2124. 3. Powles T, et al. JAMA Oncol. 2017;3:e172411. 4. Sharma P, et al. Lancet Oncol. 2017;18:312-322. 5. Bellmunt J, et al. N Engl J Med. 2017;376:1015-1026.
12-Mo OS Rate: Urothelial Carcinoma Post Platinum
Historical control withCT ~ 26%
Data not mature
70
60
50
40
30
20
10
0
39.2%
54.3%55%
43.9%
80
Patie
nts
(%)
1. Powles T, et al. Lancet. 2018;391:748-757. 2. Apolo AB, et al. J Clin Oncol. 2017;35:2117-2124. 3. Powles T, et al. JAMA Oncol. 2017;3:e172411. 4. Sharma P, et al. Lancet Oncol. 2017;18:312-322. 5. Bellmunt J, et al. N Engl J Med. 2017;376:1015-1026.
Atezolizumab[1]
IMvigor 211 Avelumab[2] Durvalumab[3]
ENRICHEDNivolumab[4]
Checkmate 275Pembrolizumab[5]
KEYNOTE 045
Currently Approved Immunotherapy inPlatinum-based Chemotherapy Progression
IMvigor130—ESMO 2019 (LBA14): presented by Dr Enrique Grande http://bit.ly/2Z1bPbD
IMvigor130 study design
Arm CPlacebo + plt/gem
Arm AAtezo + plt/gem
Arm BAtezo monotherapy
• Locally advanced or mUC• No prior systemic therapy in the metastatic setting
• ECOG PS ≤ 2• 1L platinum-eligible• N = 1200• Randomised 1:1:1
Co-primary endpoints:• INV-assessed PFSa and OS (Arm A vs C) • OS (Arm B vs C, hierarchical approach)
Stratification factors:• PD-L1 IC status (IC0 vs IC1 vs IC2/3)• Bajorin risk factor score including KPS < 80% vs
≥ 80% and presence of visceral metastases (0 vs 1 vs 2 and/or patients with liver metastases)
• Investigator choice of plt/gem (cisplatin + gem or carboplatin + gem)
Key secondary endpoints:• INV-ORRa and DOR• PFSa and OS (Arm B vs C; PD-L1 IC2/3
subgroup)• Safety
a per RECIST 1.1.
IMvigor130—ESMO 2019 (LBA14): presented by Dr Enrique Grande http://bit.ly/2Z1bPbD
IMvigor130 baseline characteristics
a n = 359 for comparisons to atezo monotherapy arm. b Per Galsky criteria per protocol, excluding New York Heart Association functional classification. c Of the patients considered cisplatin eligible at study entry, 52% received carboplatin, while 10% of patients who were cisplatin ineligible received cisplatin.
CharacteristicAtezo + plt/gem
(n = 451)Placebo + plt/gem
(n = 400)aAtezo
(n = 362)Median age (range), y 69 (31-87) 67 (33-89) 67 (36-87)ECOG PS, n (%)
0 182 (40) 173 (43) 157 (43)1 209 (46) 187 (47) 174 (48)2 60 (13) 40 (10) 31 (9)
Bajorin risk factor score, n (%)0 176 (39) 162 (41) 151 (42)1 169 (37) 149 (37) 134 (37)2 and/or liver mets 106 (24) 89 (22) 77 (21)
PD-L1 status on IC, n (%)IC2/3 108 (24) 91 (23) 88 (24)IC1 195 (43) 179 (45) 160 (44)IC0 148 (33) 130 (33) 114 (31)
Cisplatin ineligibilityb 204 (45) 140 (35) 107 (30)Renal impairment 113 (25) 94 (24) 65 (18)
Investigator choice of chemotherapyc
Carboplatin 314 (70) 264 (66) 227 (63)Cisplatin 137 (30) 136 (34) 135 (37)
IMvigor130—ESMO 2019 (LBA14): presented by Dr Enrique Grande http://bit.ly/2Z1bPbD
Final PFS: ITT (Arm A vs Arm C)
NE, not estimable. Data cutoff 31 May 2019; median survival follow-up 11.8 months (all patients).
1009080
7060504030
2010
0
PFS
(%)
0 3 6 9 12 15 18 21 24 27 30 33
MonthsNo. at Risk
6.3 mo(6.2, 7.0)
8.2 mo(6.5, 8.3)
Atezo + plt/gem 451 345 282 160 111 74 42 22 10 4 2 NEPlacebo + plt/gem 400 317 246 116 73 40 18 11 4 NE NE NE
Arm AAtezo + plt/gem
(n = 451)
Arm CPlacebo + plt/gem
(n = 400)PFS events, n (%) 334 (74) 326 (82)Stratified HR (95% CI)
0.82 (0.70, 0.96)P = 0.007 (one-sided)
IMvigor130—ESMO 2019 (LBA14): presented by Dr Enrique Grande http://bit.ly/2Z1bPbD
No. at Risk
Interim OS: ITT (Arm A vs Arm C)
Data cutoff 31 May 2019; median survival follow-up 11.8 months (all patients). a 5% of patients from Arm A and 20% of patients from Arm C received non-protocol immunotherapy. b Did not cross the interim efficacy boundary of 0.007 per the O’Brien-Fleming alpha spending function.
1009080
7060504030
2010
0
OS
(%)
0 3 6 9 12 15 18 21 24 27 30 33
Months
13.4 mo(12.0, 15.2)
16.0 mo(13.9, 18.9)
Atezo + plt/gem 451 408 360 301 229 163 117 72 36 16 3 NEPlacebo + plt/gem 400 359 308 255 182 123 79 49 25 8 NE NE
Arm AAtezo + plt/gem
(n = 451)
Arm CPlacebo + plt/gem
(n = 400)OS eventsa, n (%) 235 (52) 228 (57)Stratified HR (95% CI)
0.83 (0.69, 1.00)P = 0.027 (one-sided)b
IMvigor130—ESMO 2019 (LBA14): presented by Dr Enrique Grande http://bit.ly/2Z1bPbD
CharacteristicPatients
(n)
Arm A mOS, mo(n = 451)
Arm C mOS, mo(n = 400) HR (95% CI)a
All patients 851 16.0 13.4 0.83 (0.69, 1.00)
ECOG PS 0 355 22.0 18.2 0.83 (0.60, 1.15)1 396 14.2 10.8 0.78 (0.60, 1.01)2 100 7.4 9.3 0.99 (0.62, 1.57)
PD-L1 status 0 278 14.2 12.8 0.82 (0.60, 1.12)1 374 14.9 13.4 0.87 (0.66, 1.15)2/3 199 23.6 15.9 0.74 (0.49, 1.12)
Bajorin risk factor score 0 338 24.5 18.2 0.79 (0.57, 1.11)1 318 15.8 12.6 0.80 (0.60, 1.08)2 and/or liver
mets 195 9.5 9.5 0.94 (0.68, 1.31)
Investigator choice of chemo
Cisplatin 273 21.7 13.4 0.66 (0.47, 0.94)Carboplatin 578 14.2 13.4 0.91 (0.74, 1.14)
Interim OS subgroups: ITT (Arm A vs Arm C)
Arm C (Placebo + plt/gem) BetterArm A (Atezo + plt/gem) Better1.0
0,5
2,5
4,5
6,5
8,5
10,5
12,5
0,3 3
a Unstratified HR shown for all characteristics except for ‘All Patients’, where stratified HR is shown.
IMvigor130—ESMO 2019 (LBA14): presented by Dr Enrique Grande http://bit.ly/2Z1bPbD
Interim OS for Monotherapy: ITT (Arm B vs Arm C)
Data cutoff 31 May 2019; median survival follow-up 11.8 months (all patients). a Comparison only includes patients concurrently enrolled with Arm B.
13.1 mo(11.7, 15.1)
No. at Risk
1009080
7060504030
2010
0
OS
(%)
0 3 6 9 12 15 18 21 24 27 30 33
Months
15.7 mo(13.1, 17.8)
Atezo 360 285 245 216 173 120 72 42 16 NE NE NEPlacebo + plt/gem 359 322 274 224 158 103 62 35 15 3 NE NE
Arm BAtezo
(n = 360)
Arm CPlacebo + plt/gem
(n = 359)a
OS events, n (%) 191 (53) 198 (55)Stratified HR (95% CI) 1.02 (0.83, 1.24)
IMvigor130—ESMO 2019 (LBA14): presented by Dr Enrique Grande http://bit.ly/2Z1bPbD
Interim OS: PD-L1 status (Arm B vs Arm C)
Arm BAtezo
(n = 272)
Arm CPlacebo + plt/gem
(n = 274)OS events, n (%) 158 (58) 156 (57)Unstratified HR (95% CI) 1.07 (0.86, 1.33)
PD-L1 IC0/1
OS
(%)
Months MonthsAtezo
Placebo + plt/gem
No. at Risk272 210 175 152 124 85 48 28 11 NE NE NE274 246 212 173 116 73 41 21 10 2 NE NE
Arm BAtezo
(n = 88)
Arm CPlacebo + plt/gem
(n = 85)OS events, n (%) 33 (38) 42 (49)Stratified HR (95% CI) 0.68 (0.43, 1.08)
PD-L1 IC2/3
88 75 70 64 49 35 24 14 5 NE NE NE85 76 62 51 42 30 21 14 5 1 NE NE
Data cutoff 31 May 2019; median survival follow-up 11.8 months (all patients).
12.9 mo(11.3, 15.0)
13.5 mo(11.1, 16.4)
0 3 6 9 12 15 18 21 24 27 30 33
17.8 mo(10.0, NE)
NE(17.7, NE)
100908070605040302010
00 3 6 9 12 15 18 21 24 27 30 33
IMvigor130—ESMO 2019 (LBA14): presented by Dr Enrique Grande http://bit.ly/2Z1bPbD
IMvigor130 conclusions
• IMvigor130 is the first immune checkpoint inhibitor study to demonstrate an improvement in PFS over standard of care in 1L mUC
• At this interim analysis, clinically meaningful improvement in OS was observed with atezolizumab + plt/gem vs placebo + plt/gem but did not cross the pre-specified interim efficacy boundary; follow-up will continue to final analysis
• OS benefit of atezolizumab monotherapy vs placebo + plt/gem was greater in PD-L1-selected patients (IC2/3) than in ITT patients, although not formally tested
• Atezolizumab + plt/gem was well tolerated, with a safety profile consistent with each individual agent
• The results from IMvigor130 support atezolizumab + plt/gem as an important new treatment option for patients with untreated mUC
Algorithm for first line/second line treatment for metastatic UC fromOctober 2019 – why did it change
Atezolizumab
Pembrolizumab
Atezolizumab
Pembrolizumab
Clinical Trial(IO combinatios,fgfr inh, parp
inh, TKIs)
Modified, T. Powles, ESMO 2018
Gem/cisplatin
+ Atezolizumab?
Bladder Cancer: Spectrum of Disease
Localized: ~ 95%
NMIBC: 70%CIS, Ta, T1
MIBC: 30%T2-T4
Urology
Metastatic: ~ 5%
RadiationOncology
MedicalOncology
The Future
-Pathologist
-Radiologist
-Biologist
-Palliative care Unit
- Pain Unit
- Internist
Multidisciplinary perspectives are critical!