Largos Supervivientes, Tenemos datos? Javier Puente, MD, PhD Medical Oncology Department. Hospital Clinico San Carlos Associate Professor of Medicine. Complutense University of Madrid.
Summary
Snapshot Cancer Care 20 years ago
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
Since the 1990s: Mortality down, Survivorship Up In the United States DeSantis C, et al. CA A Cancer Journal for Clinicians 2014
Long-survivals Take into account LONG SURVIVAL? Enough Follow-up Perspective
Long-survivals 4 examples with Immunotherapy 1. Non-small cell lung cancer 2. Urothelial carcinoma 3. Renal cancer 4. Melanoma
Long-survivals 4 examples with Immunotherapy 1. Non-small cell lung cancer 2. Urothelial carcinoma 3. Renal cancer 4. Melanoma
NSCLC Lung Cancer Outcome: 8th TNM Estadio IV 38% Estadio III 31% Estadio II 7% Estadio I 24%
NSCLC Lung Cancer Outcome: first data KeyNote-001 : 3 yrs OS CA209-003 Study: 3 yrs OS 3y OS- 19% 3y OS- 18% 3y OS- 29% in PDL1 >50% Gettinger et al. JCO 2014; Leighl ASCO 2017
NSCLC Lung Cancer Outcome: first data CA209-003 Study: 5 yrs OS Brahmer, et al. AACR-2017
NSCLC Lung Cancer Outcome: first data CA209-003 Study: 5 yrs OS Brahmer, et al. AACR-2017
NSCLC Lung Cancer Outcome: first data CA209-003 Study: 5 yrs OS Brahmer, et al. AACR-2017
NSCLC Classic results with chemo Reck et al Lancet Oncol 2014; Garon et al. Lancet Oncol 2014
NSCLC Immunotherapy in pretreated patients Borghaei H, et al. ASCO 2016; Brahmer et al. AACR 2017; Herbst RS, et al. ASCO 2017; Rittmeyer A, et al. Lancet 2017
OS (%) OS (%) NSCLC Nivolumab 2L: 3 year survival rate CheckMate 017 (SQ NSCLC) CheckMate 057 (non-sq NSCLC) 100 80 Nivolumab (n = 135) Docetaxel (n = 137) HR (95% CI): 0.62 (0.48, 0.80) 100 80 Nivolumab (n = 292) Docetaxel (n = 290) HR (95% CI): 0.73 (0.62, 0.88) 60 40 No. of patients at risk 1-y OS = 42% Δ18% 2-y OS = 23% 20 1-y OS = 24% 3-y OS = 16% 20 Δ15% Δ10% 2-y OS = 8% 3-y OS = 6% 0 0 0 6 12 18 24 30 36 42 48 54 Months 1-y OS = 39% 0 6 12 18 24 30 36 42 48 54 Months No. of patients at risk 1-y OS = 51% 2-y OS = 16% 2-y OS = 29% Δ9% 3-y OS = 9% 3-y OS = 18% Nivolumab Nivolumab 135 86 57 38 31 26 21 16 8 0 292 194 148 112 82 58 49 39 7 0 Docetaxel Docetaxel 137 69 33 17 11 10 8 7 3 0 290 195 112 67 46 35 26 16 1 0 60 40 Δ12% Δ13% CI = confidence interval; HR = hazard ratio Borghaei H, et al. ASCO 2016; Brahmer et al. AACR 2017; Herbst RS, et al. ASCO 2017; Rittmeyer A, et al. Lancet 2017
NSCLC Nivolumab 2L: 3 year survival rate Felip E, et al. ESMO 2017
NSCLC Nivolumab 2L: 3 year survival rate Felip E, et al. ESMO 2017
NSCLC Nivolumab 2L: 3 year survival rate and by PD-L1 expression Felip E, et al. ESMO 2017
NSCLC Pembrolizumab 2L Keynote 010: 30-months OS (all population) Herbst at al. ASCO 2017
NSCLC Atezolizumab 2L OAK: OS ITT population at 2 years Satouchi et al. WLCC 2017
NSCLC Long survivors 1st line phase I 8 th TNM IASLC Classification, 3-y OS M1c: ~8% Eberhardt et al. JTO 2015; Leighl et al. ASCO 2017
NSCLC Long survivors 1st line phase I Keynote 024, Pembrolizumab in PD-L1 positive patients Reck, et al. NEJM 2016
NSCLC Long survivors 1st line phase I Keynote 024, Pembrolizumab in PD-L1 positive patients 2 ys OS 51.5% vs 34.5% HR 0.63 62.3% Crossover Reck, et al. NEJM 2016
NSCLC Long survivors 1st line phase I CheckMate 012: Nivolumab plus ipilimumab WLCC 2017
NSCLC Long survivors 1st line Keynote-021 Borghaei, et al. WLCC 2017
ORR, % (95% CI) NSCLC Long survivors 1st line Keynote-021 100 Δ24.8% (95% CI, 7.2% 40.9%) P = 0.0029 a 57% 37% 52% 29% 75 50 25 Median (95% CI) 19.0 (8.5 NR) 8.9 (6.2 11.8) 0 Pembrolizumab + PC PC Alone Events, n/n HR (95% CI) Pembro + PC 26/60 0.54 PC alone 40/63 (0.33 0.88) P = 0.0067 a Borghaei, et al. WLCC 2017
NSCLC Long survivors 1st line Keynote-021 77% 69% 70% 56% Median (95% CI) NR (22.8 NR) 20.9 (14.9 NR) Crossover ~ 75% Borghaei, et al. WLCC 2017
Long-survivals 4 examples with Immunotherapy 1. Non-small cell lung cancer 2. Urothelial carcinoma 3. Renal cancer 4. Melanoma
Urothelial carcinoma Percent of cases & 5-year relative survival Slide from E. Grande. Best of GU 2015
Snapshot Cancer Care 20 years ago
Urothelial carcinoma Overall survival 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
Urothelial carcinoma Overall survival Role of taxanes in the 2nd line Pal S, et al. Plos One 2015
Urothelial carcinoma Overall survival Role of vinflunine in the 2nd line Bellmunt J, et al. J Clin Oncol 2009
Urothelial carcinoma Long survivors 2nd line Keynote-045: pembrolizumab as second-line 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) Pembrolizumab 200 mg Q3W (N = 270) Investigator s Choice Paclitaxel 175 mg/m 2 Q3W or Docetaxel 75 mg/m 2 Q3W or Vinflunine 320 mg/m 2 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 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 Atezolizumab in muc: IMvigor 210 Response Rate - primary endpoint Rosenberg J, et al. Lancet 2016
Urothelial carcinoma Long survivors 2nd line Atezolizumab in muc: IMvigor 210 OS data from Atezolizumab in UBC Rosenberg J, et al. Lancet 2016
Urothelial carcinoma Long survivors 1st line Atezolizumab in muc: IMvigor 210 Balar A, et al. Lancet 2017
Urothelial carcinoma Long survivors 2nd line Atezolizumab in muc: IMvigor 210 Rosenberg J, et al. Lancet 2016
Urothelial carcinoma Long survivors 2nd line Nivolumab: phase II Check-Mate 275
Long-survivals 4 examples with Immunotherapy 1. Non-small cell lung cancer 2. Urothelial carcinoma 3. Renal cancer 4. Melanoma
Proportion surviving Kidney cancer Overall survival Surgical classic data 1.0 MSKCC classic data 0.8 0.6 7 months 0.4 0.2 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Years following systemic therapy Topalian et al. SITC 2017
Kidney cancer Overall survival CheckMate 003 Topalian et al. SITC 2017
Kidney cancer Overall survival CheckMate 025 Sharma P, et al. KCA 2017
Kidney Cancer Overall survival Hammers et al. ESMO 2016
Kidney Cancer Overall survival Hammers et al. ESMO 2016
Long-survivals 4 examples with Immunotherapy 1. Non-small cell lung cancer 2. Urothelial carcinoma 3. Renal cancer 4. Melanoma
Melanoma Overall survival Historical controls Middleton MR, et al JCO 2000
Melanoma Overall survival Ipilimumab Pool analysis Schadendorf et al. JCO 2015
Melanoma Overall survival Hodi et al. AACR 2016; Robert et al. ASCO 2016
Melanoma Overall survival CheckMate 063: Nivolumab vs Dacarbazine
Melanoma Overall survival Keynote 006: Pembrolizumab Robert et al. NEJM 2015; Schachter et al. SMR 2015
Melanoma Overall survival CheckMate 069/067: Pooled 3-year analysis Postow et al. SITC 2017
Long-survivals Expectations
Melanoma Overall survival LONG TERM SURVIVAL Schadendorf et al. JCO 2015
javierpuente.hcsc@gmail.com @docjavip