Advanced Bladder Cancer: State of the Art
Cora N Sternberg, MD, FACP Department of Medical Oncology San Camillo and Forlanini Hospitals
Rome, Italy
Rationale for immunotherapy in urothelial cancer
PD-L1/PD-1 inhibitors in urothelial cancer
Rationale for immunotherapy in urothelial cancer
PD-L1/PD-1 inhibitors in urothelial cancer
Bladder cancer
Antoni et al. Eur Urol 2017;71:96–108
Major cause of morbidity and mortality worldwide
430,000 new cases and 165,000 deaths per year
First-line randomized trials in
advanced transitional cell carcinoma
Better patient selection, earlier diagnosis and screening, better supportive care (growth factors)
Author Treatment N RR (%) MDS (months) Best arm
Loehrer MVAC
CDDP
126 120
39 12
12.5 8.2
MVAC > CDPP Logothetis MVAC
CISCA
65 55
65 46
12.6 10.0
MVAC > CISCA
Von der Maase MVAC GC
202 203
46 49
14.8 13.8
MVAC ~ GC
Sternberg HD-MVAC + G-CSF
MVAC
134 129
62 50
14.5 14.1
HD-MVAC
≥ MVAC
Bamias MVAC
+ GCSF DC + GCSF
109 111
54 37
14.2 9.3
MVAC > DC
Dreicer MVAC
PC
44 41
36 28
15.4 13.8
MVAC > PC
Bellmunt PCG
GC
312 315
57.1 46.4
15.7 12.8
PCG ~ GC
High-dose MVAC efficacy in metastatic disease:
7-year OS update
MVAC, methotrexate, vinblastine, doxorubicin and cisplatin.
HD-MVAC, methotrexate, vinblastine, doxorubicin and cisplatin Q2 W + GCSF
Sternberg CN et al. Eur J Cancer 2006;42:50–4
Time
Overall survival (%)
0 2 4 6 8 10 12
0 20 40 60 80 100
Unadjusted p=0.0417 HR=0.76 (0.58 – 0.99)
MVAC: median 14.9 months HD-MVAC: median 15.1 months 35% survival
25% survival
MVAC HD-MVAC
O N
112 129 101 134
Number at risk
32 15 11 4 2
45 29 23 8 0
Years
Number at risk
159 76 34 7 0
185 86 35 13 2
Paclitaxel/cisplatin/gemcitabine efficacy in metastatic disease (EORTC 30987)
Bellmunt J. et al. J Clin Oncol 2012;30:1107–13
Overall Log-rank test: p=0.10 Gem/Cis 247/315 12.8 months 1
Pac/Cis/Gem 239/312 15.7 months 0.86 (0.72–1.03)
14% relative reduction risk of death (n.s.)
Time (years)
0 1 2 3 4 5 6
0 20 40 60 80 100
Overall survival (%)
O N 112 129 101 134
Phase III trial of vinflunine + BSC vs BSC
*The eligible population excludes 13 patients who presented at least one major protocol violation at baseline
Bellmunt J. et al. J Clin Oncol 2009;27:4454–61; Bellmunt J. et al. Ann Oncol 2013;24:1466–72
OS in the eligible population*
Time (months) 0
Overall survival (probability)
VFL + BSC BSC
25
10 20 30 35
0 5 15
OS in the ITT population
Time (months) 0
Overall survival (probability)
VFL + BSC BSC
25
10 20 30 35
0 5 15
1.0
0.8
0.6
0.2 0.4 1.0
0.8
0.6
0.2 0.4
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)
ESMO Guidelines for diagnosis, treatment and follow-up
Bellmunt J. 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 care
Progression <12 months Second-line chemotherapy
1. Vinflunine 2. Taxane-based 3. Clinical trial
Progression >12 months 1. Platinum-based
rechallenge
First line
• FIT → CISPLATIN-based combination
• UNFIT → CARBOPLATIN-based regimen
Subsequent lines
• Vinflunine
• Taxane-based
• Platinum rechallenge
1998 2000 2002 2004 2006 2008 2010 2012 2014 2016
1996 2017
Evolution of systemic therapy for urothelial cancer
BLA, Biologics License Application
http://www.accessdata.fda.gaov/scripts/cder/drugsatfda/index.cfm; http://www.ema.europa.eu/ema/
1. Sternberg CN et al. Cancer 1989;64:2448–58; 2. McCaffrey JA et al. J Clin Oncol 1997;15:1853–7
3. von der Maase H. et al. J Clin Oncol 2005;23:4602–8; 4. Sternberg CN. et al. J Clin Oncol 2001;19:2638–46 5. Vaughn DJ et al. J Clin Oncol 2002;20:937-40; 6. Bellmunt J et al. J Clin Oncol 2009;27:4454–61
7. Rosenberg JE et al. Lancet 2016;387:1909–20; 8. Balar AV et al. Lancet 2017;389:67–76 9. Sharma P et al. Lancet Oncol 2017; doi: 10.1016/S1470-2045(17)30065-7
10. Bellmunt J et al. N Engl J Med 2017; doi: 10.1056/NEJMoa1613683 11. Balar AV et al. J Clin Oncol 2017;35(suppl 6S):Abstract 284
PublicationsRegulatory status
Cisplatin FDA approval
1978
Gemcitabine EU approval
Vinflunine EU approval
Atezolizumab FDA approval prior platinum
18 May 2016
Atezolizumab FDA 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
Nivolumab FDA approval prior platinum
02 February 2017
Pembrolizumab FDA BLA 1L cis-ineligible
AND prior platinum 03 February 2017
Avelumab FDA BLA prior platinum
28 February 2017 Pembrolizumab (1L cis-ineligible)11
Rationale for immunotherapy in urothelial cancer
PD-L1/PD-1 inhibitors in urothelial cancer
0.01 0.1 10 100 1,000
1
High mutational load in bladder cancer
Lawrence et al. Nature 2013;499:214–8
Bladder tumors along with other malignancies such as lung and melanoma display a high number of somatic mutations rendering these tumours more immunogenic
Somatic mutation frequency (/Mb)
n=22 20 52 134 26 23 81 227 91 57 121 13 63 214 11 394 219 20 49 181 231 76 88 35 335 179 121
Rhabdoid tumour Ewing sarcoma Thyroid AML Medulloblastoma Carcinoid Neuroblastoma Prostate CLL Low-grade glioma Breast Pancreas Multiple myeloma Kidney clear cell Kidney papillary cell Ovarian Glioblastoma multiforme Cervical DLBCL Head and neck Colorectal Oesophageal adenocarcinoma Stomach Bladder Lung adeno- carcinoma Lung squamous cell carcinoma Melanoma
CD8 T cell Tumour cell
MHC
PD-L1
- - -
PD-L2 PD-1
- - -
Tumor antigen
TCR
PD-1
+ + +
Expression of PDL-1 on tumour cells and macrophages suppresses
immune surveillance and permits neoplastic growth Programed cell death receptor 1 (PD-1)
is a negative co stimulatory receptor expressed primarily on activated T cells
PD-L/PD-1 binding prevents inhibits effector
T cell function: T cell break
CD8 TIL
Anti-PD1 or Anti-PDL1
Infiltration of activated T cells in TCC
Blocking PD-1 or PD-L1 releases the immunogenic break,
allowing CD8 T cells to regain the capacity to replicate and kill
Immunotherapy in urothelial cancer:
what compounds?
PD-L1 inhibitors Atezolizumab Durvalumab Avelumab PD-1 inhibitors
Nivolumab
Pembrolizumab
Immunotherapy in urothelial cancer:
what compounds?
Today’s presentation
Prior platinum 1L cis-ineligible PD-L1 inhibitors
Atezolizumab N=310 N=119
Durvalumab N=103
Avelumab N=153
PD-1 inhibitors
Nivolumab N=270
Pembrolizumab N=542 (phase III) N=370
1. Rosenberg J et al. Lancet 2016;387:1909–20; 2. Powles T et al. J Clin Oncol 2017;35(Suppl 6S):Abstract 286
3. Patel et al. J Clin Oncol 2017;35(Suppl 6S):Abstract 330; 4. Sharma P et al. Lancet Oncol 2017; doi: 10.1016/S1470-2045(17)30065-7 5. Bellmunt J et al. N Engl J Med 2017 Mar 16;376(11):1015-1026. 6. Balar A et al. Lancet 2017;389:67–76
7. Balar A et al. J Clin Oncol 2017;35(suppl 6S):Abstract 284
IMvigor210 Cohort 2: study design
• Co-primary endpoints
‒ ORR (confirmed) per RECIST v.1.1 (central independent review)
‒ Investigator-assessed ORR per modified RECIST
‒ Primary endpoints met if null hypothesis (ORR of 10%) rejected at significance level (α) of 5%
• Key secondary endpoints
‒ PFS, DOR, OS, safety
• Data previously published in The Lancet1, longer follow-up presented at ESMO 20162 (21.0 months vs 11.7 months)
IRF, independent review facility. ClinicalTrials.gov ID: NCT02108652
aPD-L1 prospectively assessed by a central laboratory, with patients and investigators blinded
bCockcroft-Gault formula
1. Rosenberg JE et al. Lancet 2016;387:1909–20; 2. Loriot Y et al. Ann Oncol 2016;27(suppl_6):783P
Cohort 2 (N=310):
Platinum-treated mUC
Atezolizumab 1,200mg IV q3w until loss of clinical benefit Cohort 1 (N=119):
1L cisplatin ineligible
Atezolizumab 1,200mg IV q3w until RECIST v1.1 progression
• Inoperable locally advanced or metastatic urothelial
carcinoma
• Predominantly UC histology
• Tumour tissue evaluable for PD-L1 testinga
Overall survival according to PD-L1 status
Rosenberg JE et al, Lancet. 2016 May 7;387(10031):1909-20
IMvigor210 Cohort 2: ORR
IRF, independent review facility
Median follow-up: 21.0 months; data cut-off: July 4, 2016 Loriot Y et al. Ann Oncol 2016;27(suppl_6):783P
• Median treatment duration was 12 weeks (range, 0 to 104) – 137 patients were treated beyond RECIST v1.1 progression
• Durable clinical benefit also observed
– Disease control rate (IRF RECIST v1.1 CR + PR + SD ≥24 weeks) of 21%
(95% CI, 17% to 26%) in all patients IC2/3 (n=100)
IC1/2/3 (n=207)
All patients
(N=310)
IC1 (n=107)
IC0 (n=103) ORR per IRF RECIST v1.1a, %
(95% CI)
28 (19, 38)
19 (14, 25)
16 (12, 20)
11 (6, 19)
9 (4, 16) CR rate per IRF RECIST v1.1, %
(95% CI)
14 (8, 22)
8 (5, 13)
6 (4, 9)
3 (1, 8)
2 (0, 7) ORR per immune-modified
RECISTb, % (95% CI)
29 (20, 39)
24 (18, 30)
20 (15, 25)
19 (12, 27)
12 (6, 19)
IMvigor210 Cohort 2: overall survival
Median follow-up: 21.0 months; data cut-off: July 4, 2016 Loriot Y et al. Ann Oncol 2016;27(suppl_6):783P
0 20 40 60 80 100
Overall survival (%)
0 4 8 12
Time (months)
16 20 24
IC0/1 (n=210)
IC2/3 (n=100)
All patients
(N=310)
Median OS, months (95% CI)
6.7 (5.4, 8.0)
11.9 (9.0, NE)
7.9 (6.7, 9.3)
12-month OS rate, % (95% CI)
31 (24, 37)
50 (40, 60)
37 (31, 42)
Number at risk
All patients 310 265 203 176 146 126 110 99 91 79 70 23 2
TCGA subtype II is associated with higher ORR
TCGA, The Cancer Genome Atlas. Data cutoff: March 14, 2016.
1. Cancer Genome Atlas Research Network Nature 2014. 2. Rosenberg Lancet 2016 Rosenberg JE et al. J Clin Oncol 2016;34(suppl):Abstract 104
0 25 50 75 100
ORR (%)
I II III IV
n=73 n=52 n=38 n=36
Luminal Basal
• Gene expression data used to classify IMvigor210 tumour samples recapitulated TCGA subtypes1,2
• Responses occurred in all subtypes, but ORR was significantly higher in
luminal II vs other subtypes (p=0.0072)
PD SD PR CR RECIST v1.1 response
Mutation load, TCGA subtype and response
• Median load (n=150) was significantly increased in responders (12·4/Mb) versus non-responders (6·4/Mb)
‒ The relationship between load and response was unrelated to TCGA subtype (p=0·2200)
CR, complete response; IC, tumour infiltrating immune cell; MB, megabase; PR, partial response; PD, progressive disease; SD, stable disease; TC, tumour cell.
Rosenberg JE et al. Lancet 2016;387:1909–20
Analysis of mutation load versus TCGA subtype and response
CheckMate 275: study design and objectives
NCT02387996
Sharma P et al. Lancet Oncol 2017 Mar;18(3):312-322.
• Primary endpoint: ORR based on blinded independent review committee (BIRC) (RECIST v1.1) evaluation in all patients and in patients with tumour PD-L1 expression
≥1% and ≥5%
Open-label, single-arm, phase II study
• Metastatic or locally advanced mUC
• Disease progression on a prior platinum-based
therapy
• Evaluable PD-L1 tumor tissue sample
Treat until progression or
unacceptable toxicity Nivolumab
3mg/kg IV q2w N=270
Blinded independent review committee (BIRC) assessment of response using
RECIST v1.1
Treatment Patients
CheckMate 275: overall survival
*Similar results were seen using the 5% PD-L1 tumour expression cut-off
Sharma P et al. Lancet Oncol 2017; Lancet Oncol 2017 Mar;18(3):312-322
Time (months)
OS estimate
1.0
0.8
0.4
0.0
0 3 6 9 15
0.6
0.2
Median OS, months (95% CI)*
All treated 8.74 (6.05–NR) PD-L1 <1% 5.95 (4.30–8.08) PD-L1 ≥1% 11.30 (8.74–NR)
12
ORR and median OS in all patients were 19.6% and 8.7 months
Number at risk
All patients 265 (0) 198 (3) 148 (4) 63 (71) 5 (125) 0 (130)
CM: 68-year-old female with metastatic TCC after GC and vinflunine
San Camilo Hospital: CheckMate 275
Nivolumab 3mg/kg q2w initiated on study on July 2015
July 2015 September 2015 April 2016
• Co-primary endpoints: OS and PFS in total and PD-L1 CPS ≥10% populations
• Secondary endpoints: ORR and DOR in total and PD-L1 CPS ≥10% populations;
safety in total population
• Urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
• Transitional cell predominant
• PD after 1–2 lines of
platinum-based chemotherapy or recurrence within 12 months of
perioperative platinum-based therapy
• ECOG PS 0–2
• Provision of tumour sample for biomarker assessment
N=542
Paclitaxel 175mg/m2 IV q3w or docetaxel 75mg/m2 IV q3w or vinflunine 320mg/m2 IV q3w
R
Pembrolizumab 200 mg IV q3w
NCT02256436
Bellmunt J et al. N Engl J Med 2017 Mar 16;376(11):1015-1026
KEYNOTE-045: study design and objectives
Stratification factors
• ECOG PS (0/1 vs 2)
• Hemoglobin level (<10 vs ≥10 g/dL)
• Liver metastases (yes vs no)
• Time from last chemotherapy dose (<3 vs ≥3 months)
Number at risk
Pembro 270 226 194 169 147 131 87 54 27 13 4 0 0 Chemo 272 232 171 138 109 89 55 27 14 3 0 0 0
KEYNOTE-045: overall survival
CPS, combined positive score (defined as percentage of PD-L1+ tumour cells (TC) and infiltrating immune cells (IC) relative to the total number of TC. High PD-L1 expression was defined as CPS ≥10%
Data cut-off date: September 7, 2016
Bellmunt J et al. N Engl J Med 2017 Mar 16;376(11):1015-1026 Median OS months
(95% CI) HR (95% CI) P Pembrolizumab 10.3 (8.0–11.8) 0.73
(0.59–0.91) 0.0022 Chemotherapy 7.4 (6.1–8.3)
Time (months) 100
0
Overall survival (%)
80 60 40 20 0
4 8 12 16 20 24
43.9%
30.7%
Time (months) 100
0
Overall survival (%)
80 60 40 20 0
4 8 12 16 20 24
39.8%
26.9%
Total population CPS ≥10%
Median OS months
(95% CI) HR (95% CI) P 8.0 (5.0–12.3) 0.57
(0.37–0.88) 0.0048 5.2 (4.0–7.4)
27% reduction in the risk of death
Pembro 74 60 51 42 35 31 18 12 7 3 0 0 0 Chemo 90 76 51 36 28 24 16 8 4 1 0 0 0
MB: 62-year-old female with Stage IV TCC with lung and liver and bladder cancer after GC
San Camilo Hospital: KEYNOTE-045
Pembrolizumab 200mg q3w initiated on study on 30 June 2015
June 2015 October 2015 December 2016
MB: 62-year-old female with Stage IV TCC with lung and liver and bladder cancer after GC
San Camilo Hospital: KEYNOTE-045
Pembrolizumab 200mg q3w initiated on study on 30 June 2015
June 2015 October 2015 December 2016
MB: 62-year-old female with Stage IV TCC with lung and liver and bladder cancer after GC
San Camilo Hospital: KEYNOTE-045
Pembrolizumab 200mg q3w initiated on study on 30 June 2015
June 2015 October 2015 December 2016
Durvalumab and avelumab in prior platinum
urothelial cancer: summary of antitumour activity
N=103
Confirmed ORR, % (95% CI) 20.4
(13.1, 29.5)
CR, % 3.9
1. Powles T et al. J Clin Oncol 2017;35(Suppl 6S):Abstract 286 2. Patel et al. J Clin Oncol 2017;35(Suppl 6S):Abstract 330
Durvalumab
1Median duration of follow-up, 8.4 months
PD-L1-high expression defined as ≥25% of tumour cells (TCs) or immune cells (ICs) staining for PD-L1; PD-L1-low/negative expression defined as <25% of both TCs and ICs staining for PD-L1
Avelumab
2N=153
Confirmed ORR, % (95% CI) 17.6
(12.0, 24.6)
CR, % 5.9
Clinical cut-off, 19 March 2016. Median duration of follow-up, 7.3 months
Immunotherapy in urothelial cancer:
what compounds?
Today’s presentation
Prior platinum 1L cis-ineligible PD-L1 inhibitors
Atezolizumab N=310 N=119
Durvalumab N=103
Avelumab N=153
PD-1 inhibitors
Nivolumab N=270
Pembrolizumab N=542 (phase III) N=370
1. Rosenberg et al. Lancet 2016;387:1909–20; 2. Powles et al. J Clin Oncol 2017;35(Suppl 6S):Abstract 286
3. Patel et al. J Clin Oncol 2017;35(Suppl 6S):Abstract 330; 4. Sharma et al. Lancet Oncol 2017; doi: 10.1016/S1470-2045(17)30065-7 5. Bellmunt et al. N Engl J Med 2017; doi: 10.1056/NEJMoa1613683; 6. Balar et al. Lancet 2017;389:67–76
7. Balar et al. J Clin Oncol 2017;35(suppl 6S):Abstract 284
IMvigor210 Cohort 1: study design
Primary endpoint
• Confirmed ORR: RECIST v1.1 (per central IRF) Key secondary endpoints
• DOR, PFS, OS, safety
IRF, independent review facility. ClinicalTrials.gov ID: NCT02108652.
aPD-L1 prospectively assessed by a central laboratory, with patients and investigators blinded
bCockcroft-Gault formula
Balar AV et al. Lancet 2017;389:67–76
Cohort 2 (N=310):
Platinum-treated mUC
Atezolizumab 1,200mg IV q3w until loss of clinical benefit Cohort 1 (N=119):
1L cisplatin ineligible
Atezolizumab 1,200mg IV q3w until RECIST v1.1 progression
• Inoperable locally advanced or metastatic urothelial
carcinoma
• Predominantly UC histology
• Tumour tissue evaluable for PD-L1 testinga
IMvigor210 Cohort 1: efficacy
Response to atezolizumab (IRF RECIST v1.1)
• Durable clinical benefit also observed
‒ Disease control rate (CR + PR + SD ≥ 24 weeks) of 30% (95% CI, 22% to 39%) in all patients
• With a median follow-up of 17.2 months, median DOR was not yet reached in any PD-L1 subgroup (median DOR range, 3.7 to 21.0 months), and 70% of responses were ongoing
aIncludes 19 patients with missing/unevaluable responses. All treated patients had measurable disease at baseline per investigator-assessed RECIST v1.1. PD-L1 IC status: IC2/3 (≥5%), IC1 (≥1% and <5%), IC0 (<1%). Data cut-off: 14 March 2016
Balar AV et al. Lancet 2017;389:67–76
IC2/3 (n=32)
IC1/2/3 (n=80)
All patients (N=119)
IC1 (n=48)
IC0 (n=39) ORRa, %
(95% CI)
28 (14, 47)
24 (15, 35)
23 (16, 31)
21 (10, 35)
21 (9, 36)
CR, % 13 10 9 8 8
IMvigor210 Cohort 1: efficacy
Overall survival (median and landmark 12-month OS)
Data cut-off: 4 July 2016
Balar AV et al. Lancet 2017;389:67–76
0 0 20 40 60 80 100
4 8 12
Time (months)
Overall survival (%)
16 20 24
Subgroup Median OS (95% Cl) 12-month OS (95% Cl) All (N=119) 15.9 months (10.4, NE) 57% (48–66) IC0/1 (n=87) 19.1 months (9.8, NE) 59% (48–70) IC2/3 (n=32) 12.3 months (6.0, NE) 52% (35–70)
Number at risk
All patients 310 265 203 176 146 126 110 99 91 79 70 23 2
KEYNOTE-052: study design
Balar AV et al. Ann Oncol 2016;27(suppl_6):LBA32_PR Balar AV et al. J Clin Oncol 2017;35(suppl 6S):Abstract 284
Pembrolizumab 200mg Q3W
• Advanced urothelial cancer
• No prior chemotherapy for metastatic disease
• ECOG PS 0-2
• Ineligible for cisplatin based on ≥1 of the following
– CrCl <60 mL/min – ECOG PS 2
– ≥ Grade 2 neuropathy or hearing loss – NYHA class III CHF
N=370
Primary endpoints
• ORR in all patients
• ORR in patients with PD-L1–positive tumours Secondary endpoints
• DOR, PFS, OS, and ORR in all patients, PD-L1 positive and PD-L1–high expressing patients; safety and tolerability;
establish an assay cut point for high PD-L1 expression
Interim analysis from the first 100 patients reported at ESMO 2016
• ORR was 24% (16–34), with a CR rate of 6%
KEYNOTE-052: confirmed objective response assessed per RECIST v1.1 by central imaging vendor review
*Total population
(N=370)
Patients enrolled
≥4 months before data
cut-off (n=307)
CPS ≥10%
(n=80)
CPS ≥10%
enrolled
≥4 months before data
cut-off (n=61) ORR, %
(95% CI)
24 (20, 29)
27 (22, 32)
39 (28, 50)
48 (35, 61)
CR, % 5 6 10 13
Clinical cut-off, 1 September 2016. Median duration of follow-up, 5 months Balar AV et al. J Clin Oncol 2017;35(suppl 6S):Abstract 284
• Median DOR for the total population was not reached (95% CI: 1+–14+ months)
‒ Median DOR for patients enrolled ≥4 months before the data cut-off was not reached (95% CI: 1+–14+ months)
• 83% of all responses were ongoing at the data cut-off (median follow-up, 5 months [range, 0.1–17 months])
• OS rate was 67% at 6 months
Phase III trials in urothelial/bladder cancer:
what’s coming up next?
Study
(NCT number) Treatment Patients
Primary endpoint 2L prior-platinum
IMvigor211 (NCT02302807)
Atezolizumab vs investigator’s choice chemotherapy (docetaxel, paclitaxel or vinflunine)
932 OS
1L
IMvigor130 (NCT02807636)
Atezolizumab vs
atezolizumab + gemcitabine + carboplatin/cisplatin vs placebo + gemcitabine + carboplatin/cisplatin
1200 PFS (combination arms), OS
KEYNOTE-361 (NCT02853305)
Pembrolizumab vs
pembrolizumab + gemcitabine + carboplatin/cisplatin vs gemcitabine + carboplatin/cisplatin
990 PFS, OS
DANUBE
(NCT02516241)
Durvalumab + tremelimumab vs durvalumab vs gemcitabine + carboplatin/cisplatin
1005 PFS, OS
Maintenance
JAVELIN bladder 100 (NCT02603432)
Avelumab + BSC vs BSC 668 OS
Adjuvant IMvigor010 (NCT02450331)
Atezolizumab vs observation 700 DFS
CheckMate 274 (NCT02632409)
Nivolumab vs placebo 640 DFS
Source: clinicaltrials.gov
