largos supervivientes, ¿tenemos datos? · rosenberg j, et al. lancet 2016 os data from...
TRANSCRIPT
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