Inmunoterapia: Presente y futuro.
Cáncer de vejiga
Enrique Grande Jefe de Servicio de Oncología Médica y Director de Investigación Clínica
MD Anderson Cancer Center Madrid
Does it make sense to use Immunotherapy in
Urothelial Tumours?
Proposed Model of BCG Therapy in Bladder Cancer
Clinical Care Options slide deck
Tcells
NeutrophilsMonocytes
Bladderurothelium
BCG Tumorcells
1.Attachmentandinvasionoftheurothelium
4.CytolysisofbladdertumorcellsbyCD8+Tcells
3.AttractionandactivationofTcells2.Attractionofinnateimmunecellsandreleaseofcytokines/chemokines
BCG in Superficial Bladder Cancer (SWOG 8216)
Lamm DL, et al. N Engl J Med 1991
100
80
60
40
20
0 6 0 12 18 24 30
BCG
Doxorubicin
Months from Registration
Dis
ease F
ree S
urv
ival
%
At Risk
28
26
Relapses
6
16
Somatic mutations can be used to indirectly estimate neoantigen burden
Alexandrov LB, et al. Nature 2013
From Chemo-based treatments to Immuno-
sensitive disease
Atezolizumab está autorizado por la Comisión Europea para el tratamiento de pacientes adultos con carcinoma urotelial localmente avanzado o metastásico (CU) después de quimioterapia previa que
contenga platino o que no son considerados aptos para el tratamiento con cisplatino. En España se encuentra pendiente del acuerdo del Precio & Reembolso con el Sistema Nacional de Salud.
Evolving Regulatory Field in Urothelial Tumors
BLA, Biologics License Application http://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;15:1853–7 3. von der Maase et al. J Clin Oncol 2005;23:4602–8; 4. Sternberg et al. J Clin Oncol 2001;19:2638–46 5. Vaughn et al. J Clin Oncol 2002;20:937–40; 6. Bellmunt et al. J Clin Oncol 2009;27:4454–61 7. Rosenberg et al. Lancet 2016;387:1909–20; 8. Balar et al. Lancet 2017;389:67–76 9. Sharma et al. Lancet Oncol 2017; doi: 10.1016/S1470-2045(17)30065-7 10. Bellmunt et al. N Engl J Med 2017; doi: 10.1056/NEJMoa1613683 11. Balar et al. J Clin Oncol 2017;35(suppl 6S):Abstract 284
1998 2000 2002 2004 2006 2008 2010 2012 2014 20161996 2017
Pub
licat
ions
Reg
ulat
ory
stat
us
Cisplatin FDA
approval
1978
Gemcitabine EU approval
Vinflunine EU approval
Atezolizumab FDA approval prior platinum
18 May 2016
AtezolizumabFDA BLA 1L cis-ineligible
09 January 2017
Docetaxel2
Standard MVAC1
1989
HD-MVAC4
Paclitaxel5
Vinflunine6
Atezolizumab
(prior platinum)7
Gemcitabine
+ cisplatin3 Pembrolizumab
(prior platinum)10
Nivolumab
(prior platinum)9
Atezolizumab
(1L cis-ineligible)8
Durvalumab FDA BLA prior platinum
09 December 2016
NivolumabFDA approval prior platinum
02 February 2017
PembrolizumabFDA BLA 1L cis-ineligible
AND prior platinum
03 February 2017
AvelumabFDA BLA prior platinum
28 February 2017
Pembrolizumab
(1L cis-ineligible)11
EMA approved drugs in 2017
1. Platinum-refractory
2. Unfit for chemo (1st Line)
1. Platinum-refractory
2. Unfit for chemo (1st Line)
ESMO Guidelines for Metastatic Bladder Cancer
Adapted from Bellmunt J, et al. Ann Oncol 2014
Setting Treatment Level ofEvidence
First Line
Cisplatin +Gemcitabine IA
MVAC(methotrexate,vinblastine, adriamycinand
cisplatin)IA
Cisplatin +Gemcitabine +Paclitaxel IB
Carboplatin +Gemcitabine IA
M-CAVI(Methotrexate/carboplatin/vinblastin)orTaxane or Gemcitabine
IIA
Second Line Vinflunine IB
Fit
UnfitLonge
r-term
survival
Role of vinflunine in 2nd line
Bellmunt , et al. J Clin Oncol 2009
OS in the eligible population*
Time (months)
1.0
0.8
0.6
0
0.2
Ov
era
ll s
urv
iva
l (p
rob
ab
ilit
y)
VFL + BSC
BSC
0.4
2510 3530200 155
OS in the ITT population
Time (months)
1.0
0.8
0.6
0
0.2
Ov
era
ll s
urv
iva
l (p
rob
ab
ilit
y)
VFL + BSC
BSC
0.4
2510 3530200 155
Median OS (ITT)
6.9 months with VFL + BSC (n=253) versus 4.6 months with BSC (n=117)
HR=0.88 (log rank p=0.2868)
Median OS (eligible)
6.9 months with VFL + BSC (n=249) versus 4.3 months with BSC (n=108)
HR=0.78 (log rank p=0.0403)
OS in the eligible population*
Time (years)
1.0
0.8
0.6
0
0.2
Ov
era
ll s
urv
iva
l (p
rob
ab
ilit
y)
VFL + BSC
BSC
0.4
2510 3530200 155
OS in the ITT population
Time (months)
1.0
0.8
0.6
0
0.2
Ov
era
ll s
urv
iva
l (p
rob
ab
ilit
y)
VFL + BSC
BSC
0.4
2510 3530200 155
Median OS (ITT)
6.9 months with VFL + BSC (n=253) versus 4.6 months with BSC (n=117)
HR=0.88 (log rank p=0.2868)
Median OS (eligible)
6.9 months with VFL + BSC (n=249) versus 4.3 months with BSC (n=108)
HR=0.78 (log rank p=0.0403)
Urothelial tract carcinoma: an unmet medical need
Pal, et al. PLoS One 2015
Disease specific survival (months)
1.0
0.8
0.2
0
Su
rviv
al
pro
ba
bilit
y
0.4
48246 543630180 60
0.6
4212
Survival in 2nd Line
n
Median (months) 1-year 2-year 3-year
1990–2000 810 4.0 21% 10% 8%
2001–2010 2,300 4.0 23% 11% 8%
Log-rank p-value: 0.1328
Not exactly the same indications by EMA
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003985/WC500189765.pdf http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/004143/WC500231701.pdf
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003820/smops/Positive/human_smop_001170.jsp&mid=WC0b01ac058001d127
• OPDIVO as monotherapy is indicated for the treatment of locally advanced unresectable or metastatic urothelial carcinoma in adults after failure of prior platinum-containing therapy
Nivolumab
• Tecentriq as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma after prior platinum-containing chemotherapy or who are considered cisplatin ineligible
Atezolizumab
• Keytruda as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy.
• Keytruda as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy.
Pembrolizumab
Checkmate 275: Nivolumab in metastatic urothelial carcinoma after platinum therapy phase 2 trial
Sharma P, et al. Lancet Oncol 2017
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Months
Pro
gre
ss
ion
-Fre
e S
urv
iva
l(P
rob
ab
ilit
y)
0 3 6 9 12No. at Risk
All treated patients 265 110 48 17 0
Median PFS, Months (95% CI)a
All treated 2.00 (1.87–2.63)
All treated
patients
PD-L1 <1%
PD-L1 <1% 1.87 (1.77–2.04)
143 49 21 9 0PD-L1 <1%
PD-L1 ≥1% 3.55 (1.94–3.71)
122 61 27 8 0PD-L1 ≥1%
PD-L1 ≥1%
Keynote 045: Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma
Bellmunt J, et al. N Engl J Med 2017
Pembrolizumab
200 mg Q3W
(N = 270)
Investigator’s Choice
Paclitaxel 175 mg/m2 Q3W or
Docetaxel 75 mg/m2 Q3W or
Vinflunine 320 mg/m2 Q3W
(N = 272)
Treated up to 24 mos or until
CR, PD, unacceptable AE, or
investigator decision*†
Treated until PD, unacceptable
AE, or patient withdrawal of
consent
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)
Keynote 045: PFS and OS of Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma
Bellmunt J, et al. N Engl J Med 2017
Keynote 045: OS benefit over each of the individual agents
Petrylak D, et al. ESMO 2017
Imvigor 210: Atezolizumab in Urothelial Cancer
Rosenberg J, et al. Lancet 2016
Imvigor 210: Atezolizumab in Urothelial Cancer
Rosenberg J, et al. Lancet 2016
Imvigor 210: Overall Response Rate - primary endpoint (platinum resistant)
Dreicer et al. ASCO 2016
IC2/3n = 100
IC1/2/3n = 207
Alla
N = 310
ORR: confirmed IRF RECIST v1.1 (95% CI)
28%(19, 38)
19%(14, 25)
16%(12, 20)
CR rate: confirmed IRF RECIST v1.1 (95% CI)
15%(9, 24)
9%(6, 14)
7%(4, 10)
IC1n = 107
IC0n = 103
11%(6, 19)
9%(4, 16)
4%(1, 9)
2%(0, 7)
• ResponseswereseeninallICsubgroups,butORRwasenrichedwithhigherPD-L1status• Completeresponsesaccountedfornearlyhalfoftheobservedresponses
– CRswereobservedinallPD-L1subgroups,withthehighestrateinIC2/3patients
• ORRsperimmune-modifiedRECISTwereconcordant
Imvigor 210: Overall Response Rate - primary endpoint (platinum resistant)
• Median time to first
responsea
was 2.1 mo
‒ Range, 1.6 to 8.3 mo
• Additional CRs and PRs
were observed with
longer follow-up
‒ 5 PR-to-CR and 2 SD-to-
PR conversions
Months
0 2 4 6 8 10 12 14 16 18 20
Pa
tien
ts W
ith C
R o
r P
R a
s B
est
Re
spo
nse
Median follow-up: 17.5 months
(range, 0.2 to 21.1+ mo)
CR as Best Response
PR as Best Response
First CR/PR
Treatment Discontinuationb
Ongoing Responsec
First Responses
a Per IRF RECIST v1.1 b Discontinuation
symbol does not indicate timing. c No PD or death only. Data cutoff: March 14,
2016.
Dreicer et al. ASCO 2016
Imvigor 210: PFS data from Atezolizumab in UBC
Rosenberg J, et al. ECCO 2015
IC2/3 (n=100)
IC0/1 (n=211)
All (n=311)
Median PFS,* months (95% CI) 2.1 (2.1, 4.1) 2.1 (2.0, 2.1) 2.1 (2.1, 2.1)
PF
S e
stim
ate
2 6 113 8 9
2.1
4 5 7 10
2.1
0
1.0
0.8
0.6
0.4
0.2
0
Time (months)
1
IC2/3 (n=100)
IC0/1 (n=211)
Imvigor 210: OS data from Atezolizumab in UBC
Oral presentation of Dr. D. Petrylak at 17th Annual Meeting of the Society of Urologic Oncology (SUO 2016) – November 30-December 2, 2016, San Antonio, TX
IMvigor211: A Phase III Randomized Study Examining Atezolizumab vs. Chemo for Platinum-Treated adv. UC
Powles T, et al. EAS 2017, IMvigor211
Key Eligibility Criteriaa
• mUC with progression during or
following platinum-based chemotherapy
– ≤ 2 prior lines of therapy
• Measurable disease per RECIST v1.1
• ECOG PS 0-1• Evaluable sample for PD-L1 testing
• TCC histology as primary component
(N = 931)
§ Primary endpoint
– OS, tested hierarchically
in pre-specified populations
Atezolizumab 1200 mg q3w
R
1:1No crossover permitted
per protocolSurvival
follow-up
Loss of clinical benefit
RECIST v1.1
progression
Stratification Factors• No. of risk factorsb (0 vs. 1/2/3)
• Liver metastases (yes vs. no)
• PD-L1 status (0/1 vs. 2/3)
• Chemotherapy (vinflunine vs. taxanes)
§ Additional endpoints
– Efficacy: RECIST v1.1 ORR, PFS and DORc
– Safety
– PROs: EORTC QLQ-C30
Chemotherapy (investigator ’s choice)
• Vinflunine q3w
• Docetaxel q3w
• Paclitaxel q3w
IMvigor211: OS Analysis in the Intention to Treat (ITT) Population
Powles T, et al. EAS 2017, IMvigor211 § Median follow-up duration in ITT population: 17.3 mo (range, 0 to 24.5 mo)
Events/Patients
Median OS(95% CI)
12-mo OS Rate(95% CI)
Atezolizumab 324/467 8.6 mo (7.8, 9.6) 39% (35, 44)
Chemotherapy 350/464 8.0 mo (7.2, 8.6) 32% (28, 37)80
60
0
10 12 14 16 18 202 4 6 80 2422
20
40
Ove
rall
Su
rviv
al
100
Months
80
60
0
10 12 14 16 18 202 4 6 80 2422
20
40
Ove
rall
Su
rviv
al
100
Months
HR = 0.85 (95% CI: 0.73, 0.99)
P = 0.038
No. at Risk
Atezolizumab 467 405 327 280 245 201 177 138 90 59 34 13 1
Chemotherapy 464 397 330 268 219 175 140 99 60 42 17 7 1
Key secondary endpoints: ORR, then PFS
Primary endpoint:
OS
OS: IC2/3
OS: IC1/2/3
OS: ITT
PFS: IC2/3
PFS: IC1/2/3
PFS: ITT
ORR: IC2/3
ORR: IC1/2/3
ORR: ITT
2-sided = 0.05
IMvigor211: Study Design
Powles T, et al. EAS 2017, IMvigor211
IMvigor211: OS Analysis in IC2/3 Population
Powles T, et al. EAS 2017, IMvigor211
HR = 0.87 (95% CI: 0.63, 1.21)
P = 0.41
Events/Patients
Median OS(95% CI)
12-mo OS Rate(95% CI)
Atezolizumab 72/116 11.1 mo (8.6, 15.5) 46% (37, 56)
Chemotherapy 88/118 10.6 mo (8.4, 12.2) 41% (32, 50)
No. at Risk
Atezolizumab 116 100 85 77 71 58 51 39 27 19 11 6 0
Chemotherapy 118 100 91 82 71 61 47 32 24 15 9 5 1
80
60
0
10 12 14 16 18 202 4 6 80 2422
20
40
Ove
rall S
urv
iva
l100
Months
Diferencia no significativa: no se alcanzó el objetivo primario del estudio.
IMvigor211: OS by Chemotherapy Type
Powles T, et al. EAS 2017, IMvigor211
§ OS was also examined in subgroups based on chemotherapy
type at randomization
– Improved OS was observed
with atezolizumab vs. taxanes
ITT With Taxane
SubgroupMedian OS
(95% CI)
Atezolizumab 9.2 mo (7.9, 10.4)
Vinflunine 8.3 mo (6.9, 9.6)
SubgroupMedian OS
(95% CI)
Atezolizumab 8.3 mo (6.6, 9.8)
Taxane 7.5 mo (6.7, 8.6)
No. at Risk
Atezolizumab 215 186 153 125 106 89 81 66 45 34 19 7 0
Taxane 214 179 147 122 94 74 58 35 20 16 4 3 1
80
60
0
10 12 14 16 18 202 4 6 80 2422
20
40
Ove
rall
Su
rviv
al
100
Months
No. at Risk
Atezolizumab 252 219 174 155 139 112 96 72 45 25 15 6 1
Vinflunine 250 218 183 146 125 101 82 64 20 26 13 4 0
80
60
0
10 12 14 16 18 202 4 6 80 2422
20
40
Ove
rall
Su
rviv
al
100
Months
HR = 0.97 (95% CI: 0.78, 1.19)
ITT With Vinflunine
HR = 0.73 (95% CI: 0.58, 0.92)
Resultados exploratorios al no haberse alcanzado el objetivo primario del estudio.
IMvigor211: Responses by PDL1 subgroup and Duration of Response
Powles T, et al. EAS 2017, IMvigor211
12 14
Months
Confirmed ORRa
IC2/3 IC1/2/3 ITT
Atezo (n = 113)
Chemo (n = 116)
Atezo (n = 312)
Chemo (n = 306)
Atezo (n = 462)
Chemo (n = 461)
Responders, n (%) 26 (23%) 25 (22%) 44 (14%) 45 (15%) 62 (13%) 62 (13%)
95% CI, % 16, 32 15, 30 10, 19 11, 19 11, 17 11, 17
CR, n (%) 8 (7%) 8 (7%) 11 (4%) 13 (4%) 16 (3%) 16 (3%)
§ Objective response was similar between arms
§ Responses to atezolizumab were durable
regardless of PD-L1 status
– 63% of patients in the
atezolizumab arm and
21% in the chemotherapy
arm had ongoing responses
at data cutoff
DOR in ITT Population
No. at Risk
Atezolizumab 62 61 56 50 42 35 23 14 9 5 2 0
Chemotherapy 62 62 59 40 28 23 16 8 5 4 0 0
Events/Patients mDOR (95% CI)
Atezolizumab 23/62 21.7 mo (13.0, 21.7)
Chemotherapy 49/62 7.4 mo (6.1, 10.3)
80
60
0
10 12 14 16 18 202 4 6 80 22
20
40O
bje
ctiv
e R
esp
on
se
100
Months
IMvigor211: Treatment Related Adverse Events
Powles T, et al. EAS 2017, IMvigor211
Treatment-Related AEs in ≥ 10% (All Grade) or ≥ 4% (Grades 3-4) for Either Arm
ChemotherapyAtezolizumab
Proportion of Patients (%)
30% 30%10%10% 0%40% 40%20%20%
■■ All Grade
■■ Grade 3-4
IMvigor211: Patient Related Outcomes
Powles T, et al. EAS 2017, IMvigor211
EORTC QLQ-C30 Scales: Change From C1D1
Better
Worse
Better
Worse
n = 385 329 254 223 201 162 157 144 122 107 105 91 91 84 79 73 72 67 69 65 56 46 38 32 25 22 19 16 13 10 9 8 4 1
n = 350 302 202 186 169 107 92 83 56 43 39 33 31 24 18 16 14 12 11 9 8 6 5 5 4 5 5 3 2 1 1 1 1
Cycle No.
n = 379 328 250 222 197 162 156 143 120 106 104 90 90 82 78 71 71 66 68 64 55 45 37 31 23 21 19 16 13 10 9 8 4 1
n = 349 299 203 185 169 106 90 82 55 42 38 32 30 24 17 15 13 12 11 9 8 6 5 5 4 5 5 3 2 1 1 1 1
What’s behind the curves?
Enrique Grande
• 64 y.o. male
• Cystectomy for Urothelial Bladder Carcinoma in 2011 pT2N0
• Lung and Lymph nodes mets. October 2014
• Cisplatin + Gemcitabine x 6 (ends April 2015)
• Liver, lung and lymph progression July 2015
• We recruited the patient for the IMvigor210 trial
July 2015
Sept 2015
Oct 2015
What’s behind the curves?
Enrique Grande
July 2015
Sept 2015
Oct 2015
What’s behind the curves?
Enrique Grande
Oct 2015
Sept 2015
July 2015
1. Platinum-refractory
2. Unfit for chemo (1st Line)
ESMO Guidelines for Metastatic Bladder Cancer
Adapted from Bellmunt J, et al. Ann Oncol 2014
Setting Treatment Level ofEvidence
First Line
Cisplatin +Gemcitabine IA
MVAC(methotrexate,vinblastine, adriamycinand
cisplatin)IA
Cisplatin +Gemcitabine +Paclitaxel IB
Carboplatin +Gemcitabine IA
M-CAVI(Methotrexate/carboplatin/vinblastin)orTaxane or Gemcitabine
IIA
Second Line Vinflunine IB
Fit
UnfitLonge
r-term
survival
Urothelial tract carcinoma: 1st Line Outcome
von der Maase, et al. J Clin Oncol 2005 De Santis, et al. J Clin Oncol 2012
Galsky, et al. Lancet Oncol 2011
‘Fit’ for Cisplatin Cisplatin ineligible (unfit)
Median OS 8.1m 9.3m
Treatment of Elderly or Unfit Patients with Urothelial Tumors: the Biggest Challenge and Opportunity
Bellmunt J, et al. Eur J Cancer 2016
Keynote 052: Pembrolizumab as First-Line Therapy in Cisplatin-ineligible Advanced Urothelial Cancer
Balar AV, et al. Lancet Oncol 2017
Imvigor 210: Atezolizumab in Urothelial Cancer
Balar AV, et al. Lancet Oncol 2017
Imvigor 210: First-line Atezolizumab in Cisplatin-Ineligible Metastatic Urothelial Carcinoma (Cohort 1)
Balar AV, et al. Lancet Oncol 2017
Imvigor 210 Cohort 1: Overall Response Rate
Balar AV, et al. Lancet Oncol 2017
Imvigor 210 Cohort 1: Change in tumor burden in patients with objective response
Bellmunt J; et al. Poster presentation at NCRI 2016
Imvigor 210: Atezolizumab in Urothelial Cancer
Balar AV, et al. Lancet Oncol 2017
NCCN Guidelines 2017 v.5
https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf
What’s behind the curves?
Enrique Grande
• 62 y.o male
• Morbid obesity
• DM type II under insulin treatment
• Renal impairment: creatinine clearance 43 ml/min
• Cystectomy due to uncontrolled bladder bleeding in July 2015
• Staging CT scan: liver and lymph nodes metastasis (Aug 2015)
What’s behind the curves?
Enrique Grande
Aug 2015
What’s behind the curves?
Enrique Grande
Aug 2015 Nov 2015
What’s behind the curves?
Enrique Grande
Aug 2015
What’s behind the curves?
Enrique Grande
Aug 2015 Nov 2015
What’s behind the curves?
Enrique Grande Aug 2015
What’s behind the curves?
Enrique Grande Aug 2015 Nov 2015
IMvigor 210 (Cohort 1): Monitoring of Renal Function in Patients Treated with Atezolizumab
Bellmunt J; et al. Poster presentation at NCRI 2016
Phase III: avelumab (EudraCT 2015-003262-86)
Phase II: regorafenib (NCT02459119)
Phase II: pembrolizumab
• Atezo + BCG
• Pembrolizumab
• Everolimus + intravesical GEM (NCT01259063)
Pembrolizumab + RT (NCT02560636)
PURE01: pembrolizumab>cystectomy (EudraCT: 2015-002055-10)
ABACUS: atezolizumab>cystectomy
Phase III: atezolizumab (NCT02450331)
Phase III: avelumab (EudraCT 2015-003262-86)
Phase III: nivolumab (CA209-274)
Neoadjuvant Adjuvant
BCG refractory
Phase II: KEYNOTE-052, pembrolizumab
(NCT02335424)
Phase III: KEYNOTE-045, pembrolizumab vs chemo
(NCT02256436)
Phase III: (GO29294), atezolizumab vs chemo, (NCT02302807)
Phase III: DANUBE: MEDI4736 vs MEDI4736 + tremelimumab vs chemo(NCT02516241)
Maintenance Tx
Refractory
Phase III: Ramucirumab + docetaxel
(NCT02426125)
Phase III: IMVIGOR 130: atezolizumab vs chemo + atezolizumab vs chemo
Phase III: MK3475-361: pembrolizumab vs chemo + pembrolizumab vs chemo
A continuous evolving field
Sources: http://ClinicalTrials.gov Usos experimentales, no autorizados.
This is a matter of opportunity
Rosemberg JE, et al. Lancet 2016 Bellmunt , et al. J Clin Oncol 2009
OS in the eligible population*
Time (months)
1.0
0.8
0.6
0
0.2
Ov
era
ll s
urv
iva
l (p
rob
ab
ilit
y)
VFL + BSC
BSC
0.4
2510 3530200 155
OS in the ITT population
Time (months)
1.0
0.8
0.6
0
0.2
Ov
era
ll s
urv
iva
l (p
rob
ab
ilit
y)
VFL + BSC
BSC
0.4
2510 3530200 155
Median OS (ITT)
6.9 months with VFL + BSC (n=253) versus 4.6 months with BSC (n=117)
HR=0.88 (log rank p=0.2868)
Median OS (eligible)
6.9 months with VFL + BSC (n=249) versus 4.3 months with BSC (n=108)
HR=0.78 (log rank p=0.0403)
?
Conclusions and Remaining Challenges
• Atezolizumab, pembrolizumab and nivolumab are now approved by EMA for the
treatment of platinum-resistant urothelial carcinomas
• Atezolizumab and pembrolizumab are also approved but patients ‘unfit’ for
cisplatinum in 1st line
• Unfortunately, there’s a clear lack of reliable Biomarkers
• We still don’t know the future and synergy of novel combinations
o Chemo
o Other IOs like CTLA4, IDO1, LAG3, TIGIT, etc
o Targeted agents
• We need experience for the assessment of response/clinical benefit in daily practice