Largos Supervivientes,

¿Tenemos datos? Javier Puente, MD, PhD

Medical Oncology Department. Hospital Clinico San Carlos

Associate Professor of Medicine. Complutense University of Madrid.

Summary

Cancer Care 20 years ago

Snapshot

Cancer Genomics

Advent of the “precision medicine” era

But cancer´s biology is far more complex than we had imagined

Schilsky R. ASCO 2016

Rise of Immunotherapy

Game-changing discoveries-more coming

Schilsky R. ASCO 2016

Mortality down, Survivorship Up

Since the 1990s:

In the United States…

DeSantis C, et al. CA A Cancer Journal for Clinicians 2014

Take into account…

Long-survivals

LONG

SURVIVAL

? Enough Follow-up

Perspective

4 examples with Immunotherapy

Long-survivals

1. Non-small cell lung cancer

2. Urothelial carcinoma

3. Renal cancer

4. Melanoma

4 examples with Immunotherapy

Long-survivals

1. Non-small cell lung cancer

2. Urothelial carcinoma

3. Renal cancer

4. Melanoma

Lung Cancer Outcome: 8th TNM

NSCLC

Estadio I 24%

Estadio II 7%

Estadio III

31%

Estadio IV

38%

Lung Cancer Outcome: first data

NSCLC

CA209-003 Study: 3 yrs OS

3y OS- 18%

3y OS- 19%

3y OS- 29% in PDL1 >50%

KeyNote-001 : 3 yrs OS

Gettinger et al. JCO 2014; Leighl ASCO 2017

Lung Cancer Outcome: first data

NSCLC

CA209-003 Study: 5 yrs OS

Brahmer, et al. AACR-2017

Lung Cancer Outcome: first data

NSCLC

CA209-003 Study: 5 yrs OS

Brahmer, et al. AACR-2017

Lung Cancer Outcome: first data

NSCLC

CA209-003 Study: 5 yrs OS

Brahmer, et al. AACR-2017

Classic results with chemo

NSCLC

Reck et al Lancet Oncol 2014; Garon et al. Lancet Oncol 2014

Immunotherapy in pretreated patients

NSCLC

Borghaei H, et al. ASCO 2016; Brahmer et al. AACR 2017; Herbst RS, et al. ASCO 2017; Rittmeyer A, et al. Lancet 2017

Nivolumab 2L: 3 year survival rate

NSCLC

Borghaei H, et al. ASCO 2016; Brahmer et al. AACR 2017; Herbst RS, et al. ASCO 2017; Rittmeyer A, et al. Lancet 2017

CI = confidence interval; HR = hazard ratio

135 86 57 38 31 26 21 16 8 0

137 69 33 17 11 10 8 7 3 0

CheckMate 017 (SQ NSCLC)

No. of patients at risk

Nivolumab

Docetaxel

0 6 12 18 24 30 36 42 48 54

Δ10%

Nivolumab (n = 135)

Docetaxel (n = 137)

1-y OS = 42%

2-y OS = 23%

3-y OS = 16% 1-y OS = 24%

2-y OS = 8% 3-y OS = 6%

HR (95% CI): 0.62 (0.48, 0.80)

100

80

60

40

20

0

OS

(%)

Months

Δ18%

Δ15%

292 194 148 112 82 58 49 39 7 0

290 195 112 67 46 35 26 16 1 0

CheckMate 057 (non-SQ NSCLC)

No. of patients at risk

Nivolumab

Docetaxel

0 6 12 18 24 30 36 42 48 54

Months

1-y OS = 51%

2-y OS = 29%

3-y OS = 18%

1-y OS = 39%

2-y OS = 16% 3-y OS = 9%

Nivolumab (n = 292)

Docetaxel (n = 290)

HR (95% CI): 0.73 (0.62, 0.88)

100

80

60

40

20

0

OS

(%)

Δ12%

Δ13%

Δ9%

Nivolumab 2L: 3 year survival rate

NSCLC

Felip E, et al. ESMO 2017

Nivolumab 2L: 3 year survival rate

NSCLC

Felip E, et al. ESMO 2017

Nivolumab 2L: 3 year survival rate and by PD-L1 expression

NSCLC

Felip E, et al. ESMO 2017

Pembrolizumab 2L

NSCLC

Keynote 010: 30-months OS (all population)

Herbst at al. ASCO 2017

Atezolizumab 2L

NSCLC

OAK: OS ITT population at 2 years

Satouchi et al. WLCC 2017

Long survivors 1st line phase I

NSCLC

Eberhardt et al. JTO 2015; Leighl et al. ASCO 2017

8th TNM IASLC Classification, 3-y OS M1c: ~8%

Long survivors 1st line phase I

NSCLC

Reck, et al. NEJM 2016

Keynote 024, Pembrolizumab in PD-L1 positive patients

Long survivors 1st line phase I

NSCLC

Reck, et al. NEJM 2016

Keynote 024, Pembrolizumab in PD-L1 positive patients

2 ys OS 51.5% vs 34.5%

HR 0.63 62.3% Crossover

Long survivors 1st line phase I

NSCLC

WLCC 2017

CheckMate 012: Nivolumab plus ipilimumab

Long survivors 1st line

NSCLC

Keynote-021

Borghaei, et al. WLCC 2017

Long survivors 1st line

NSCLC

Keynote-021

Median (95% CI)

19.0 (8.5–NR)

8.9 (6.2–11.8)

57%

37%

52%

29%

Events,

n/N HR (95% CI)

Pembro + PC 26/60 0.54

(0.33–0.88)

P = 0.0067a PC alone 40/63

0

25

50

75

100

Pembrolizumab+ PC

PCAlone

OR

R, %

(9

5%

CI)

Δ24.8%

(95% CI, 7.2%‒40.9%)

P = 0.0029a

Borghaei, et al. WLCC 2017

Long survivors 1st line

NSCLC

Borghaei, et al. WLCC 2017

Keynote-021

77%

69% 70%

56%

Median (95% CI)

NR (22.8–NR)

20.9 (14.9–NR) Crossover ~ 75%

4 examples with Immunotherapy

Long-survivals

1. Non-small cell lung cancer

2. Urothelial carcinoma

3. Renal cancer

4. Melanoma

Percent of cases & 5-year relative survival

Urothelial carcinoma

Slide from E. Grande. Best of GU 2015

Cancer Care 20 years ago

Snapshot

Overall survival

Urothelial carcinoma

‘Fit’ for Cisplatin Cisplatin ineligible (unfit)

Median OS 8.1m 9.3m

von der Maase, et al. J Clin Oncol 2005

De Santis, et al. J Clin Oncol 2012

Galsky, et al. Lancet Oncol 2011

Overall survival

Urothelial carcinoma

Pal S, et al. Plos One 2015

Role of taxanes in the 2nd line

Overall survival

Urothelial carcinoma

Bellmunt J, et al. J Clin Oncol 2009

Role of vinflunine in the 2nd line

Keynote-045: pembrolizumab as second-line

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)

Bellmunt J, et al. NEJM 2017

Urothelial carcinoma

Long survivors 2nd line

Bellmunt J, et al. NEJM 2017

Urothelial carcinoma

Long survivors 2nd line

Petrylak, et al. ESMO 2017

Urothelial carcinoma

Long survivors 2nd line

Rosenberg J, et al. Lancet 2016

Response Rate - primary endpoint

Urothelial carcinoma

Long survivors 2nd line

Atezolizumab in mUC: IMvigor 210

Rosenberg J, et al. Lancet 2016

OS data from Atezolizumab in UBC

Urothelial carcinoma

Long survivors 2nd line

Atezolizumab in mUC: IMvigor 210

Balar A, et al. Lancet 2017

Urothelial carcinoma

Long survivors 1st line

Atezolizumab in mUC: IMvigor 210

Atezolizumab in mUC: IMvigor 210

Rosenberg J, et al. Lancet 2016

Urothelial carcinoma

Long survivors 2nd line

Nivolumab: phase II Check-Mate 275

Urothelial carcinoma

Long survivors 2nd line

4 examples with Immunotherapy

Long-survivals

1. Non-small cell lung cancer

2. Urothelial carcinoma

3. Renal cancer

4. Melanoma

Overall survival

Kidney cancer

Surgical “classic data”

Topalian et al. SITC 2017

MSKCC “classic data”

0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Years following systemic therapy

Pro

po

rtio

n s

urv

ivin

g

7 months

Overall survival

Kidney cancer

CheckMate 003

Topalian et al. SITC 2017

Overall survival

Kidney cancer

CheckMate 025

Sharma P, et al. KCA 2017

Overall survival

Kidney Cancer

Hammers et al. ESMO 2016

Overall survival

Kidney Cancer

Hammers et al. ESMO 2016

4 examples with Immunotherapy

Long-survivals

1. Non-small cell lung cancer

2. Urothelial carcinoma

3. Renal cancer

4. Melanoma

Overall survival

Melanoma

Historical controls

Middleton MR, et al JCO 2000

Overall survival

Melanoma

Ipilimumab Pool analysis

Schadendorf et al. JCO 2015

Overall survival

Melanoma

Hodi et al. AACR 2016; Robert et al. ASCO 2016

Overall survival

Melanoma

CheckMate 063: Nivolumab vs Dacarbazine

Overall survival

Melanoma

Keynote 006: Pembrolizumab

Robert et al. NEJM 2015; Schachter et al. SMR 2015

Overall survival

Melanoma

CheckMate 069/067: Pooled 3-year analysis

Postow et al. SITC 2017

Expectations

Long-survivals

Overall survival

Melanoma

LONG TERM SURVIVAL

Schadendorf et al. JCO 2015

javierpuente.hcsc@gmail.com

@docjavip