Immunotherapy Advances in Uro-Oncology

Immunotherapy and Uro-Oncology
Dr Alok Gupta
MD, DM,
Consultant Medical Oncologist
Max Super Speciality Hospital, Saket
Ex-Asst. Professor, AIIMS, New Delhi

Outline
2
1. Immunotherapy in Bladder Cancer
2. Immunotherapy in Kidney Cancer
3. Immunotherapy in Prostate cancer

Role of immune system in advanced Bladder Cancer
Martincorena I, Campbell PJ.Science.2015;349:1483-9
High mutational load may correlate with immunogenicity, and provides valuable prognostic information
3

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 Setting
Post-Platinum Frontline Cisplatin
Ineligible
Atezolizumab[1] PD-L1 Q3W Accelerated Accelerated
Avelumab[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

Post-Platinum Urothelial Carcinoma: ORR
CT: ~
10%
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]
ORR(%,95%CI)
Data from separate studies. Not head-to-head comparisons.
13.4 18.2 17.8 19.6 21.1
0
10
20
30
40
50
60
70
Pembrolizumab[5]Nivolumab[4]Durvalumab[3]Avelumab[2]

Post-Platinum Urothelial Carcinoma: OS at 12 Mos
1. Powles T, et al. Lancet. 2018;391:748-757. 2. Apolo AB, et al. J Clin Oncol. 2017;35:2117-2124.
3. O’Donnell P, et al. AACR 2018. Abstract CT031. 4. Sharma P, et al. AACR 2018. Abstract CT178.
5. Bellmunt J, et al. N Engl J Med. 2017;376:1015-1026.
CT: ~
26%
Atezolizumab[1]
OS(%,95%CI)
Data from separate studies. Not head-to-head comparisons.
39.2 54.3 46.6 40.3 43.9
0
10
20
30
40
50
60
70
Pembrolizumab[5]Nivolumab[4]Durvalumab[3]Avelumab[2]

IMvigor 210: Study Design
• Single-arm phase II study with 2 cohorts
Pts with inoperable
advanced or metastatic UC,
predominantly TCC
histology, evaluable tumor
tissue for
PD-L1 testing
Cohort 1 Previously
untreated,
cisplatin ineligible
Cohort 2 Prior
platinum treatment
Atezolizumab 1200
mg IV Q3W
until PD
Atezolizumab 1200
mg IV Q3W
until loss of benefit
Rosenberg JE, et al. Lancet. 2016;387:1909-1920
Primaryendpoints: confirmed ORRby RECISTv1.1 (per central review), ORRper immune- modified RECIST(per
investigator)
Secondaryendpoints: DoR,PFS,OS,safety
7

Cohort 1 : Cisplatin ineligible – Survival
• No clear difference in OS between PD-L1 subgroups
• Median OS was not reached in patients with no risk factors
• 13·4 months in patients with one risk factor (either visceral metastases or ECOG 2)
• 6·2 months in patients with two risk factors
• 19·1 months median OS reported in the stable disease subgroup
8

Cohort 2: Post platinum – Responses
• Responses seen in all PD-L1 IC subgroups; higher response seen with higher PD-L1 status
• After a median follow-up of 11·7 months, the median duration of response was not yet reached in any of the PD-L1
subgroups (range 2·0–13·7months)
• At the time of the updated data cutoff, ongoing responses were reported in 38 (84%) of the 45 responding patients
• The median time to response was 2·1 months (95% CI2·0–2·2)
9

Was the accelerated approval too early?

IMvigor211 Study Design
 Primary endpoint
 OS, tested hierarchically
in pre-specified populations
Atezolizumab
1200 mgq3w
R
1:1
No crossoverpermitted per
protocol
Survival
follow-up
Lossof
clinical benefit
RECISTv1.1
progression
KeyEligibility Criteria
• mUCwith progression during orfollowing
platinum-based chemotherapy
– ≤ 2 prior lines of therapy
• Measurable diseaseper RECISTv1.1
• ECOGPS0-1
• Evaluablesamplefor PD-L1testing
• TCChistology asprimary component
(N =931)
StratificationFactors
• No. of risk factorsa(0 vs.1/2/3)
• Liver metastases(yesvs. no)
• PD-L1status (0/1 vs.2/3)
• Chemotherapy (vinflunine vs. taxanes)
 Additional endpoints
 Efficacy: RECIST v1.1 ORR, PFS and DOR
 Safety
 PROs: EORTC QLQ-C30
Chemotherapy
(investigator’s choice)
• Vinflunineq3w
• Docetaxelq3w
• Paclitaxelq3w
aDefinedby time from prior chemotherapy<3 mo, ECOGperformancestatus>0 and hemoglobin <10 g/dL.

OS Analysis: IC2/3 Population
20
Events/
Patients
Median OS
(95%CI)
12-mo OSRate
(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)
10 12 14 16 18 208
HR = 0.87 (95% CI: 0.63, 1.21)
P = 0.41
0 2 4 6 2422
100
OverallSurvival
80
60
40
20
0
No. atRisk Month s
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

IMvigor211 – Conclusion
• The primary endpoint of OS was not met in the IC2/3 population
• Due to delayed separation of the Kaplan-Meier curves, the differences in
mOS and HR do not fully reflect the clinical activity achieved with
atezolizumab
• The safety data showed no new safety signals and demonstrateda more
favorable safety profile for atezolizumab than for chemotherapy

KEYNOTE-045: Study Design
 International, randomized, open-label phase III study
 Primary endpoints: OS, PFS
 Secondary endpoints: ORR, DoR, safety
Bellmunt J, et al. N Engl J Med. 2017;376:1015-1026.
Adult patients with
predominantly transitional
cell UC of the renal pelvis,
ureter, bladder, or urethra;
PD after
1-2 lines of platinum-based
CT or recurrence < 12 mos
after perioperative
platinum-based CT; ECOG
PS 0-2(N = 542)
Treatment continued
for 2 yrs or until PD,
unacceptable toxicity,
or withdrawal of
consent
Pembrolizumab
200 mg IV Q3W
(n = 270)
Paclitaxel 175 mg/m2 IV Q3W or
Docetaxel 75 mg/m2 IV Q3W or
Vinflunine 320 mg/m2 IV Q3W
(n = 272)
Stratified by ECOG PS (0/1 vs 2), Hg (< 10 vs ≥ 10
g/dL), liver mets (yes vs no), and time since last CT (<
vs ≥ 3 mos)

Pembrolizum
ab
Chemotherap
y
KEYNOTE-045: OS
270 194 147 116 98 67 23
272 171 109 73 58 35 13
44.4%
30.3% 33.2%
19.7%
Median OS, Mos (95% CI)
10.3 (8.0-12.3)
7.4 (6.3-8.3)
0 4 8 12 16 20 24 28 32
0
20
40
60
80OS(%)
Mos
100
Patients at Risk, n
de Wit R, et al. ESMO 2017. Abstract LBA37_PR.
Data cutoff: May 19,
2017
HR: 0.70 (0.57-0.86; P = .0003)

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 Targe
t
Schedul
e
FDA Approval Type by Setting
Post-Platinum Frontline Cisplatin
Ineligible
Atezolizumab[1] PD-L1 Q3W Accelerated Accelerated
Avelumab[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

First-line Therapy for Metastatic UC: What We
Know
 Chemotherapy is active in this space
 Cisplatin-eligible patients should get cisplatin
 FDA and EMA warn of decreased survival with first-line
atezolizumab or pembrolizumab in cisplatin-ineligible patients
with low PD-L1, as assessed by an appropriate companion
diagnostic test
‒ Access to such diagnostic tests is variable, limited at many
institutions

Characteristic
Pembrolizumab
(n = 43)[1]
Atezolizumab
(n = 68)[2]
Eligibility criteria T2-T3b; N1 allowed T2-T4a; N0 only
Cisplatin eligible, % 100 0
Received neoadjuvant
CT, %
12 0
Duration of neoadjuvant
checkpoint inhibition
3 cycles (9 wks) 2 cycles (6 wks)
Safe Yes Yes
Pathological CR (pT0), % 40 29
Available biomarker data Yes Yes
Neoadjuvant Checkpoint Inhibition in Bladder
Cancer: Early Results of Phase II Trials
1. Necchi A, et al. ASCO 2018. Abstract 4507. 2. Powles T, et al. ASCO 2018. Abstract 4506.
Encouraging results; long-term outcomes needed before clinical use
pT0 Rates
With CT:
Gem/Cis,
15% to 32%
DD MVAC,
26% to 43%

Summary
• We have 5 IO drugs with some data for use in mUC but only
one with phase III trial data to support its use
(Pembrolizumab)
• Biomarker studies seem to show a relationship but not clear
• Accelerated approval does not guarantee phase 3 trial success
• More IO drugs and combination trials are ongoing
• Cost will play a big role in its usage and access in non reimbursable
markets

Outline
20

Role of immune system in Kidney Cancer
23

Immunotherapy in Advanced RCC:
A Renewed Level of Interest?
LevelofResearch
< 1980s 1992 2000 2009 2015
High-dose IL-2
IFN-α and IL-2–based
regimens
Rise of the targeted therapies
Bevacizumab +
IFN-α
 Checkpoint inhibitors
 Vaccines*
 Recombinant T-cell
receptors*
 Bispecific T-cell engagers*
*Not approved for metastatic RCC as of January 2016.
Slide credit: clinicaloptions.com
McDermott DF, et al. Semin Oncol. 2013;40:492-498.
Figure adapted from L Harshman, MD

CheckMate-025: Nivolumab in Previously Treated
Metastatic RCC
 Primary endpoint: OS
 Secondary endpoints: PFS, ORR, OR duration, Safety
Motzer R, et al. N Engl J Med. 2015;373:1803-1813.
Nivolumab
3 mg/kg IV every 2 wks
Everolimus
10 mg PO daily
Metastatic RCC with ≤ 2 prior
antiangiogenic therapies and
≤ 3 total prior systemic regimens
(N = 821)
Slide credit: clinicaloptions.com

CheckMate-025: OS
Nivolumab (n = 410) 25.0 (21.8-NE)
Everolimus (n = 411) 19.6 (17.6-23.1)
HR: 0.73 (98.5% CI: 0.57-0.93; P = .0018)
0 3 6 129 15
Mos
18 21 24 27 30 33
Pts at Risk, n
Nivolumab 410 389 359 337 305 275 213 139 73 29 3 0
411 366 324 287 265 241 187 115 61 20 2 0Everolimus
0
30
10
20
40
50
60
70
80
90
100
OS(%)
Nivolumab
Everolimus
Motzer R, et al. N Engl J Med. 2015;373:1803-1813. Slide credit: clinicaloptions.com

CheckMate-025: OS by PD-L1 Expression
PD-L1 < 1%
(n = 575/756, 76%)
Nivolumab 21.8 (16.5-28.1)
Everolimus 18.8 (11.9-19.9)
Pts at Risk, n
Nivolumab 94 86 79 73 66 58 45 31 18 4 1 0
Everolimus 97 77 68 59 52 47 40 19 9 4 1 0
Nivolumab
Everolimus
PD-L1 ≥ 1%
(n = 181/756, 24%)
Nivolumab 27.4 (21.4-NE)
Everolimus 21.2 (17.7–26.2)
276 265 245 233 210 189 145 94 48 22 2 0
299 267 238 214 200 192 137 92 51 16 1 0
Nivolumab
Everolimus
HR: 0.78
(95% CI: 0.53-1.16)
HR: 0.76
(95% CI: 0.60-0.97)
Motzer R, et al. N Engl J Med. 2015;373:1803-1813. Slide credit: clinicaloptions.com
0
0 3 6 129 15
Mos
18 21 24 27 30 33
30
10
20
40
50
60
70
80
90
100
OS(%)
0
0 3 6 129 15
Mos
18 21 24 27 30 33
30
10
20
40
50
60
70
80
90
100

Recent updates in the treatment of mRCC
2015 2016
Nivolumab
November 2015
Second Line
April 2016
Cabozantinib
Second Line
May 2016
Lenvatinib
Second Line
CABOSUN trial
ESMO 2016
Phase II Trial of
Cabozantinib vs Sunitinib
for Patients with
Previously Untreated
aRCC
S-TRAC trial
ESMO 2016
Sunitinib in Adjuvant
setting
2017
Check Mate 214
ESMO 2017
Nivo+Ipi vs Sunitinib for Treatment-
Naïve mRCC
IMmotion trial
ASCO GU 2017
atezolizumab as
monotherapy or in
combination with
bevacizumab vs
sunitinib in patients
with previously
untreated mRCC
2018
Nivolumab + Ipilumab
FDA approval for first line
intermediate and poor risk
mRCC

TreatmentPatients
Randomise 1:1
CheckMate 214: Study design
IMDC, International Metastatic RCC Database Consortium; KPS, Karnofsky performance status; PD-L1, programmed cell death ligand 1; Q2W, every 2
weeks; Q3W, every 3 weeks.
Escudier B, et al. LBA5. Presented at ESMO 2017, Madrid, Spain, 8–12 September, 2017.
 Treatment-naïve
advanced or
metastatic
clear-cell RCC
 Measurable disease
 KPS ≥70%
 Tumour tissue
available for
PD-L1 testing
Treatment until
progression or
unacceptable
toxicity
Arm A
3 mg/kg nivolumab IV +
1 mg/kg ipilimumab IV Q3W for
four doses, then
3 mg/kg nivolumab IV Q2W
Arm B
50 mg sunitinib orally once daily
for 4 weeks
(6-week cycles)
Stratified by
 IMDC prognostic
score (0 vs
1–2 vs 3–6)
 Region (US vs
Canada / Europe vs
Rest of World)
NCT02231749
Co-primary endpoints
In IMDC intermediate- and
poor-risk patients
ORR (per IRRC)
PFS (per IRRC)
OS
Statistical analyses
Overall alpha is 0.05, split among the three co-primary
endpoints
0.001 for ORR, 0.009 for PFS, and 0.04 for OS

 Significantly improved ORR and CR rates (both P < .0001) with nivo
+ ipi vs sun in IMDC intermediate-/poor-risk pts
 ORR most improved in pts with tumor PD-L1 ≥ 1% (58% vs 22%; P <
.0001)
Escudier B, et al. ESMO 2017. Abstract LBA5.
Response per IRRC,* %
Nivo + Ipi
(n = 425)
Sunitinib
(n = 422)
ORR 42 27
 CR 9 1
 PR 32 25
 SD 31 45
 PD 20 17
 NR/unable to determine 8 12
CheckMate 214: ORR in IMDC Poor-
/Intermediate-Risk Patients

0 3 6 9 12 15 18 21 24 27 30
Progression-FreeSurvival(Probability)
425 304 233 187 163 149 118 46 17 3 0
422 282 191 139 107 86 57 33 11 1 0
No. at Risk
NIVO + IPI
SUN
Months
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Co-primary endpoint
PFS per IRRC: IMDC intermediate/poor risk
Hazard ratio (99.1% CI), 0.82 (0.64–1.05)
P=0.0331
Median PFS, months (95% CI)
NIVO + IPI 11.6 (8.7–15.5)
SUN 8.4 (7.0–10.8)
CI, confidence interval; IMDC, International Metastatic RCC Database Consortium; IPI, ipilimumab; NIVO, nivolumab;
IRRC, independent radiology review committee; NE, not estimable; NR, not reported; OS, overall survival; SUN, sunitinib.
NCT02231749

Hazard ratio (99.8% CI), 0.63 (0.44–0.89)
P<0.0001
Median OS, months (95% CI)
NIVO + IPI NR (28.2–NE)
SUN 26.0 (22.1–NE)
Overallsurvival(probability)
425 399 372 348 332 318 300 241 119 44 2 0
422 387 352 315 288 253 225 179 89 34 3 0
Months
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
18 21 24 27 30 3315129630
Co-primary endpoint
OS: IMDC intermediate/poor risk
CI, confidence interval; IPI, ipilimumab; NIVO, nivolumab; NE, not estimable; NR, not reported; OS, overall survival; SUN, sunitinib.
NCT02231749
No. at Risk
NIVO + IPI
SUN

N=249a
Outcome
NIVO + IPI
n=125
SUN
n=124
Confirmed ORR,b % (95% CI) 29 (21–38) 52 (43–61)
P=0.0002
PFS,c median (95% CI), months
15.3 (9.7–20.3) 25.1 (20.9–NE)
HR (99.1% CI) 2.18 (1.29–3.68)
P<0.0001
Exploratory endpoint
ORR and PFS: IMDC favourable risk
a11% of patients in both arms had tumour PD-L1 expression ≥1%; bIRRC-assessed by RECIST v1.1; cIRRC-assessed.
CI, confidence interval; IMDC, International Metastatic RCC Database Consortium; HR, hazard ratio; IPI, ipilimumab; NIVO, nivolumab;
NE, not estimable; NR, not reported; ORR, objective response rate; PFS, progression-free survival; SUN, sunitinib.
NCT02231749

NIVO + IPI
n=547
SUN
n=535
Event, % Any grade Grade 3–5 Any grade Grade 3–5a
Treatment-related adverse events in ≥25%
of patients
93 46 97 63
Fatigue 37 4 49 9
Pruritus 28 <1 9 0
Diarrhoea 27 4 52 5
Nausea 20 2 38 1
Hypothyroidism 16 <1 25 <1
Decreased appetite 14 1 25 1
Dysgeusia 6 0 33 <1
Stomatitis 4 0 28 3
Hypertension 2 <1 40 16
Mucosal inflammation 2 0 28 3
Palmar-plantar erythrodysesthesia syndrome 1 0 43 9
Treatment-related AEs leading to discontinuation, % 22 15 12 7
Treatment-related deaths n=7b n=4c
Treatment-related adverse events:
All treated patients
NCT02231749
aTwo patients had grade 5 cardiac arrest. bPneumonitis, immune-mediated bronchitis, lower GI haemorrhage, hemophagocytic syndrome, sudden death, liver toxicity, lung
infection. cCardiac arrest (n=2), heart failure, multiple organ failure.
AE, adverse event; IPI, ipilimumab; NIVO, nivolumab; SUN, sunitinib.

NIVO + IPI
n=547
Category, % Any grade Grade 3–4
Rash 17 3
Diarrhoea/colitis 10 5
Hepatitis 7 6
Nephritis and renal dysfunction 5 2
Pneumonitis 4 2
Hypersensitivity/infusion reaction 1 0
Hypothyroidism 19 <1
Hyperthyroidism 12 <1
Adrenal insufficiency 8 3
Hypophysitis 5 3
Thyroiditis 3 <1
Diabetes mellitus 3 1
Immune-mediated adverse events:
All treated patients
 60% of patients treated with NIVO + IPI required systemic corticosteroids for an adverse event
 Secondary immunosupression with infliximab (3%) and mycophenolic acid (1%) was reported
NCT02231749
Immune-mediated AE analyses included events, regardless of causality, occurring <100 days of the last dose. These analyses were
limited to patients who received immune modulating medication for treatment of the event, except endocrine events that were included
in the analysis regardless of treatment since these events are often managed without immunosuppression
IPI, ipilimumab; NIVO, nivolumab; SUN, sunitinib.

Atezolizumab + Bevacizumab vs Sunitinib
for Untreated Advanced RCC (IMmotion151)
 Randomized, open-label phase III study
 Primary endpoints: PFS (investigator assessed) in PD-L1+ pts, OS in ITT pts
– PD-L1+ defined as ≥ 1% staining on tumor-infiltrating immune cells by IHC
 Secondary endpoints: PFS in ITT pts, OS in PD-L1+ pts, ORR, DoR, PFS and
ORR (IRC assessed), pt-reported outcomes, safety
Motzer RJ, et al. ASCO GU 2018. Abstract 578.
Treatment-naive pts with advanced
or metastatic RCC of clear cell
and/or sarcomatoid histology, KPS
≥ 70, and tissue available for PD-
L1 staining
(N = 915)
Atezolizumab 1200 mg IV Q3W +
Bevacizumab 15 mg/kg IV Q3W
(n = 454)
Sunitinib 50 mg/day PO
4 wks on, 2 wks off
(n = 461)
Stratified by MSKCC risk score,
liver metastases, PD-L1 (< 1% vs ≥
1%)

IMmotion 151: Survival
 PFS benefit with atezolizumab + bevacizumab may
increase as PD-L1 expression increases
Motzer RJ, et al. ASCO GU 2018. Abstract 578.
Outcome, Mos Atezo + Bev Sunitinib HR (95% CI) P Value
Median PFS by
investigator
 PD-L1+*†
 ITT
11.2
11.2
7.7
8.4
0.74 (0.57-0.96)
0.83 (0.70-0.97)
.02
--
Median PFS by IRC
 PD-L1+†
 ITT
8.9
9.6
7.2
8.3
0.93 (0.72-1.21)
0.88 (0.74-1.04)
--
--
Median OS‡
 PD-L1+†
 ITT*
NR
NR
23.3
NR
0.68 (0.46-1.00)
0.81 (0.63-1.03)
--
.09*Coprimary endpoint. †Investigators and IRC blinded to PD-L1 status. ‡OS data are immature.

Summary
41
• IO has an established role in the treatment of mRCC (
Nivolumab)
• New standard established with recent IO data in first line
mRCC ( int/ poor risk)
• A number of ongoing studies in the first line setting with IO
combination studies show promise
• Cost and access present a major challenge which needs to
be overcome

Outline
42

Role of immune system in Prostate Cancer
43

PD-1 Inhibition in MMR-Deficient Cancers
Le DT, et al. ASCO 2016. Abstract 103. Le DT, et al. N Engl J Med. 2015;372:2509-2520.
Radiographic Response With Pembrolizumab
-
100
MMR-P CRC
MMR-D CRC
MMR-D non-CRC
ChangeFromBLinthe
SumofLongest
Diameters(%)
20% increase (PD)
10
0
0
50
-50 30% decrease (PR)
Biochemical Response With Pembrolizumab
MMR-P CRC
MMR-D CRC
MMR-D non-CRC
ChangeinTumor
MarkerLevel(%)
Days
0% (no change)
20
0
0
-
100 0 100 200 400300
100
Pt
PFS(%)
PFS with Pembrolizumab
Mos
MMR-D
(mPFS: NR)
100
50
0
0 3 6 12 15 18 21 24 27 30
MMR-P
(mPFS: 2.3 mos)
9
OS(%)
Mos
MMR-D
(mOS: NR)
OS with Pembrolizumab100
50
0
0 3 6 12 15 18 21 24 27 30
MMR-P
(mOS: 5.98 mos)
9

KEYNOTE-016: Responses to
Pembrolizumab in MMR-Deficient Tumors
 Radiographic responses across 12 tumor types at 20 wks (N = 86)
Le DT, et al. Science. 2017;357:409-413.
Ampulla of Vater
Cholangiocarcinoma
Colorectal
Endometrial cancer
Gastroesophageal
Neuroendocrine
Osteosarcoma
Pancreas
Prostate
Small Intestine
Thyroid
Unknown primary
100
50
0
-50
-100
ChangeFrom
BaselineSLD(%)
Prostat
e
Prostat
e
(n = 1)

MMR Mutations in mCRPC
 3/150 (2%) had MMR mutations
 4/150 (2.7%) were MSI-high
Patient Cases With DNA Repair Defects
Reprinted from Robinson D, et al. Integrative clinical genomics of advanced prostate cancer. Cell.
2015;161(5):1215-1228. Copyright © 2015 with permission from Elsevier Inc.

Thank You
Dr Alok Gupta MD, DM,
Consultant Medical Oncologist
Max Super Speciality Hospital, Saket
Phone No. 9167164364
Email: alokgupta16@yahoo.co.in

Immunotherapy Advances in Uro-Oncology

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