4 ΣΥΜΠΟΣΙΟ ΚΛΙΝΙΚΗΣ ΟΓΚΟΛΟΓΙΑΣ ΡΟΔΟΥ: Εξελίξεις στη...
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Transcript of 4 ΣΥΜΠΟΣΙΟ ΚΛΙΝΙΚΗΣ ΟΓΚΟΛΟΓΙΑΣ ΡΟΔΟΥ: Εξελίξεις στη...
ΕΞΕΛΙΞΕΙΣ ΣΤΗ ΘΕΡΑΠΕΙΑ ΤΟΥ ΠΛΑΚΩΔΟΥΣ ΚΑΡΚΙΝΟΥ ΠΝΕΥΜΟΝΟΣΚΑΛΤΣΑΣ ΣΕΡΑΦΕΙΜ ΠΑΘΟΛΟΓΟΣ/ΟΓΚΟΛΟΓΟΣ
Lung Cancer Remains Major Global Health Burden One of the most common cancers and leading cause
of cancer deaths in US and worldwide[1,2]
– New cases, 2015 (estimated): US, 221,200; global, 2M
– Deaths, 2015 (estimated): US, 158,040; global, 1.5M
5-yr US survival rates[3]
– Overall: 18%
– Metastatic: 4%
1. GLOBOSCAN Cancer Fact Sheets. 2012. 2. Siegel RL, et al. CA Cancer. 2015; 65:5-29. 3. Surveillance, Epidemiology, and End Results (SEER) Program. Slide credit: clinicaloptions.com
Traditional View of Lung Cancer
American Cancer Society database.Wahbah M, et al. Ann Diagn Pathol. 2007;11:89-96.
85% of lung cancers are NSCLC
AdenocarcinomaSquamous cell carcinomaLarge cell carcinomaOther or not otherwise specified
40%20%
10% to 15%
25% to 30%
AdenocarcinomaSquamous cellLarge cell
454035302520151050
Can
cer I
ncid
ence
(%)
Yr of Diagnosis (3-Yr Moving Average)
1980
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
2002
Slide credit: clinicaloptions.com
Li T, et al. J Clin Oncol. 2013;31:1039-1049.
Evolution of NSCLC Subtyping to a Multitude of Molecular-Defined Subsets
NSCLCas one disease
Histology-Based Subtyping
Squamous34%
Other11%
Adenoca55%
Adenocarcinoma
Squamous Cell Cancer
ALKHER2BRAFPIK3CAAKT1MAP2K1NRASROS1RETEGFRKRASUnknown
EGFRvIIIPI3KCAEGFRDDR2FGFR1 AmpUnknown
First-targeted txALKEGFR
Slide credit: clinicaloptions.com
Biopsy: Establish Diagnosis, Determine Histologic Subtype, Molecular Testing Adequate tissue for histologic subtyping, molecular analysis critical
Histologic subtyping: squamous or nonsquamous?
Determination of EGFR mutation, ALK, and ROS1 translocations indicated in all nonsquamous cancers
– Should other genes be evaluated? KRAS, BRAF, HER2, RET, others?
– Should these genes be evaluated in squamous NSCLC?
Rebiopsy at time of progression
– Helps in determining resistance in EGFR-mutated and ALK+ cases
Bone biopsy (for molecular testing) contraindicated due to decalcification and degradation of DNA
Liquid biopsies (cell-free DNA in plasma) increasingly used
Slide credit: clinicaloptions.com
ΘΕΡΑΠΕΥΤΙΚΕΣ ΕΠΙΛΟΓΕΣ ΣΤΟ ΠΛΑΚΩΔΕΣ CA ΠΝΕΥΜΟΝΟΣ:ΧΗΜΕΙΟΘΕΡΑΠΕΙΑ
1.0
0.8
Schiller JH, et al. N Engl J Med. 2002;346:92-98.
Therapeutic Plateau in Metastatic NSCLCECOG 1594
Slide credit: clinicaloptions.com
0.6
0.4
0.2
00 5 10 15 20 25 30
Mos
Ove
rall
Surv
ival
(%)
Cisplatin/paclitaxel
Cisplatin/gemcitabine
Cisplatin/docetaxel
Carboplatin/paclitaxel
Cisplatin + Pemetrexed vs Cisplatin + Gemcitabine in Advanced NSCLC Randomized, noninferiority phase III study
Chemotherapy naive stage IIIB-IV NSCLC,
ECOG PS 0-1(N = 1725)
Cisplatin 75 mg/m2 on Day 1 +Pemetrexed 500 mg/m2 on Day 1
(n = 862)
Cisplatin 75 mg/m2 on Day 1 +Gemcitabine 1250 mg/m2 on Days
1 and 8(n = 863)
Stratified by stage, PS, history of brain metastasis, sex, pathologic diagnosis,
center
Vitamin B12, folate, and dexamethasone administered in both arms
Scagliotti GV, et al. J Clin Oncol. 2008;26:3543-3551. Slide credit: clinicaloptions.com
1.0
0.8
0.6
0.4
0.2
0
Cisplatin + Pemetrexed vs Cisplatin + Gemcitabine: OS by Histology
Mos
Surv
ival
Pro
babi
lity
SquamousNonsquamous
Mos
Surv
ival
Pro
babi
lity
Scagliotti GV, et al. J Clin Oncol. 2008;26:3543-3551.
C/PC/G
C/P vs C/G
Median Survival, Mos11.810.4Adjusted HR: 0.81(95% CI: 0.70-0.94)
C/PC/G
C/P vs C/G
Median Survival, Mos9.410.8Adjusted HR: 1.23(95% CI: 1.00-1.51)
1.0
0.8
0.6
0.4
0.2
0300 6 12 18 24 300 6 12 18 24
No difference in overall group between study arms: C/P 10.3 mos vs C/G 10.3 mos; adjusted HR: 0.94 (95% CI: 0.84-1.05)
Slide credit: clinicaloptions.com
Carboplatin/Albumin-Bound Paclitaxel vs Carboplatin/Paclitaxel in Advanced NSCLC
Phase IIIPrimary endpoint: ORRSecondary endpoints: PFS, OS, safety
Pts with stage IIIb/IV NSCLC, ECOG PS
0-1, no previous chemotherapy for metastatic disease
(N = 1050)
Albumin-bound Paclitaxel 100 mg/m2 on Days 1, 8, 15 +Carboplatin AUC 6 on Day 1
No premedication
Paclitaxel 200 mg/m2 on Day 1 +Carboplatin AUC 6 on Day 1
Premedication: dexamethasone, antihistamines
Stratified by stage (IIIb vs IV), age (< 70 yrs vs > 70 yrs), sex,
histology (squamous vs nonsquamous), geographic region
21-day cycles
Socinski MA, et al. J Clin Oncol. 2012;30:2055-2062. Slide credit: clinicaloptions.com
P = .005RRR: 1.3133%
25%
Intent to Treat
Socinski MA, et al. J Clin Oncol. 2012;30:2055-2062.
Carboplatin/Albumin-Bound Paclitaxel vs Carboplatin/Paclitaxel: Response
Carboplatin/albumin-bound paclitaxelCarboplatin/paclitaxel
Res
pons
e R
ate
(%)
P < .001RRR: 1.680
P = .808RRR: 1.034
41%
26%24% 25%
0
10
20
30
40
50
Squamous* Nonsquamous*229 221 292 310
*Not a prespecified endpoint. Interaction P value for histology = .036
521 531n =
Slide credit: clinicaloptions.com
ITT nab-P/Carbo
Paclitaxel/ Carbo
HR P Value
N/events 521/360 531/384
Median OS, mos (95% CI)
12.1(10.8-12.9)
11.2(10.3-12.6)
0.922(0.797-1.066)
.271
Carboplatin/Albumin-Bound Paclitaxel vs Carboplatin/Paclitaxel: OS
Squamous Cell
nab-P/Carbo
Paclitaxel/ Carbo
HR P Value
N/events 229/170 221/173
Median OS, mos (95% CI)
10.7(9.4-12.5)
9.5(8.6-11.6)
0.890(0.719-1.101)
.284
Prob
abili
ty o
f Sur
viva
l
Mos
0
0.25
0.50
0.75
1.00 nab-P/carbo (n = 521)Paclitaxel/carbo (n = 531)
330 3 6 9 12 15 18 21 24 27 30Pr
obab
ility
of S
urvi
val
Mos
0
0.25
0.50
0.75
1.00
330 3 6 9 12 15 18 21 24 27 30
nab-P/carbo (n = 229)Paclitaxel/carbo (n = 221)
Socinski MA, et al. J Clin Oncol. 2012;30:2055-2062. Slide credit: clinicaloptions.com
ΘΕΡΑΠΕΥΤΙΚΕΣ ΕΠΙΛΟΓΕΣ ΣΤΟ ΠΛΑΚΩΔΕΣ CA ΠΝΕΥΜΟΝΟΣ:ΣΤΟΧΕΥΜΕΝΗ ΘΕΡΑΠΕΙΑ
Radiographic tumor assessment (investigator read): at baseline and every 6 wks until PDMandatory tissue collection
SQUIRE: Gemcitabine/Cis + Necitumumab vs Gemcitabine/Cis in Stage IV NSCLC
Phase III Primary endpoint: OS
Necitumumab 800 mg Days 1, 8Gemcitabine 1250 mg/m² Days 1, 8
Cisplatin 75 mg/m² Day 1(N = 545)
maximum of 6 cycles
Stage IV squamous
NSCLCECOG PS 0-2
(N = 1093)
Necitumumab 800 mg Days 1, 8
Gemcitabine 1250 mg/m² Days 1, 8Cisplatin 75 mg/m² Day 1
(N = 548)
Thatcher N, et al. Lancet Oncol. 2015;16:763-774.
21-day cycles;
Treatment continued until PD or
intolerable AEs
Slide credit: clinicaloptions.com
SQUIRE: Overall Survival
Thatcher N, et al. Lancet Oncol. 2015;16:763-774. Slide credit: clinicaloptions.com
100
80
60
40
20
0403632280 4 8 12 16
Gemcitabine/cisplatin + necitumumab Censored ptsGemcitabine/cisplatinCensored pts
24
OS
(%)
Pts censored, n (%)Median OS, mos (95% CI)Stratified P value (log rank)Stratified HR (95% CI)
127 (23)11.5 (10.4-12.6)
.010.84 (0.74-0.96)
Gemcitabine/Cisplatin +
Necitumumab(n = 545)
Gemcitabine/ Cisplatin (n = 548)106 (19)
9.9 (8.9-11.1)
20Mos
SWOG S089: Carbo/Pac ± Bevacizumab ± Cetuximab in Advanced NSCLC Randomized phase III trial
Primary endpoints: OS (total); PFS in EGFR-positive pts
Secondary endpoints: OS and PFS by bevacizumab use, safety
Exploratory endpoint: OS in EGFR+ and squamous pts
Advanced NSCLC(N = 1313)
PaclitaxelCarboplatin
Bevacizumab* (n = 657)
PaclitaxelCarboplatinCetuximab
Bevacizumab* (n = 656)
Herbst RS, et al. WCLC 2015. Abstract 3612.
Bevacizumab*
Cetuximab Bevacizumab*
*In appropriate pts.
Stratified by appropriate for bevacizumab treatment
(yes/no), smoking status, stage (M1a vs M1b)
Slide credit: clinicaloptions.com
SWOG S089: Carbo/Pac ± Bevacizumab ± Cetuximab: OS
OS
(%)
HR: 0.94 (95% CI: 0.84-1.06; P = .34)
Herbst RS, et al. WCLC 2015. Abstract 3612. Slide credit: clinicaloptions.com
100
80
60
40
20
0120 3624 6048
Mos After Registration
Cetuximab armControl arm
N656657
Events, n536558
Median OS, Mos
10.99.4
95% CI 9.6-12.08.7-10.3
SWOG S089: OS in EGFR-Positive Squamous NSCLC
Herbst RS, et al. WCLC 2015. Abstract 3612. Slide credit: clinicaloptions.com
100
80
60
40
20
00 12 24 36 48 60
Mos
OS
(%)
HR: 0.56 (95% CI: 0.37-0.84; P = .006)
N Events, n Median OS, Mos 95% CI
Cetuximab arm 55 50 11.8 8.6-13.5
Control arm 56 52 6.4 4.2-8.7
REVEL: Docetaxel ± Ramucirumab in Second-line NSCLC: Study Design
Ramucirumab: VEGFR2 antibody
Primary endpoint: OS
Secondary endpoints: PFS, ORR, safety, pt-reported outcomes
Stage IV NSCLC after 1 platinum- based chemo ± maintenance,
prior Bev allowed,all histologies,
ECOG PS 0 or 1(N = 1253)
Treatment until disease
progression or unacceptable
toxicity
Stratified by ECOG PS 0 vs 1,sex, prior maintenance,
East Asia vs ROW
Ramucirumab 10 mg/kg + Docetaxel 75 mg/m2 q3w
(n = 628)
Placebo +Docetaxel 75 mg/m2 q3w
(n = 625)
Garon EB, et al. Lancet. 2014;384:665-673.
Phase III study
Slide credit: clinicaloptions.com
100
80
60
40
20
0
REVEL: Docetaxel ± Ramucirumab in Second-line NSCLC: Response
First study in the second-line setting to show an OS advantage for the addition of a “targeted” agent to docetaxel compared with docetaxel alone
First and only study of angiogenesis inhibition in advanced NSCLC to show a benefit in a squamous cell cancer cohort
Phase III Study Ram + Doc
Pl + Doc
HRP Value
ORR, %(95% CI)
22.9(19.7-26.4)
13.6(11.0-16.5)
< .001
Median PFS, mos(95% CI)
4.5 (4.2-5.4)
3.0 (2.8-3.9)
0.72 < .0001
Median OS, mos(95% CI)
10.5(9.5-11.2)
9.1(8.4-10.0)
0.86.0235
Perol M, et al. ASCO 2014. Abstract LBA8006^.
0 3 6 9 12 15 18 21 24 27 30 33 36Survival Time (Mos)
OS
(%)
Ram + DocPl + Doc
Slide credit: clinicaloptions.com
REVEL: Overall Survival
Garon EB, et al. Lancet. 2014;384:665-673. Slide credit: clinicaloptions.com
0 3 6 9 12 15 18 21 24 27 30 33 360
20
40
60
80
100O
S (%
)
Mos
Ram + DocPbo + DocCensored
Ram + DocPbo + DocRam + Doc vs Pbo + Doc:HR: 0.857 (95% CI: 0.759-0.979; P = .0235)
10.5 (9.5-11.2)9.1 (8.4-10.0)
31.827.0
Median (95% CI)Censoring Rate,
%
LUX-Lung 8: Afatinib vs Erlotinib Study Design
*Dose escalation to 50 mg and dose reduction to 30 or 20 mg permitted. †Dose reduction to 100 or 50 mg permitted. Tumor assessment at baseline, Wks 8, 12, 16; every 8 wks thereafter.
SCC of the lung (stage IIIB/IV);; progressed after ≥ 4 cycles of a first-line platinum
doublet; ECOG PS 0-1; adequate organ function
(N = 795)
Afatinib 40 mg* QD(n = 398)
Erlotinib 150 mg† QD(n = 397)
Stratified by East Asian vs non-East Asian
Primary endpoint: PFS by independent review
Secondary endpoints: OS, ORR, DCR, tumor shrinkage, PRO, safety
Soria JC, et al. Lancet Oncol. 2015;16:897-907. Slide credit: clinicaloptions.com
LUX-Lung 8: Response
Duration of response was 7.29 mos for afatinib and 3.71 mos for erlotinib
P = .055
p=0.002
Soria JC, et al. Lancet Oncol. 2015;16:897-907. Slide credit: clinicaloptions.com
P = .00260
0
10
20
30
40
50
Disease Control Rate Objective Response Rate
AfatinibErlotinib50.5
39.5
5.5 2.8
Patie
nts
(%)
LUX-Lung 8: Overall Survival
Median follow-up: 18.4 mosSoria JC, et al. Lancet Oncol. 2015;16:897-907. Slide credit: clinicaloptions.com
1.0
0.8
0.6
0.4
0.2
0
OS
(%)
0 3 6 9 12 15 18 21 24 27 30Mos
AfatinibErlotinib
36.4%
28.2%22.0%
14.4%
Median OS, mos 7.9 6.8
HR (95% CI) = 0.81 (0.69-0.95; P = .008)
Afatinib (n = 398)
Erlotinib(n = 397)
ΘΕΡΑΠΕΥΤΙΚΕΣ ΕΠΙΛΟΓΕΣ ΣΤΟ ΠΛΑΚΩΔΕΣ CA ΠΝΕΥΜΟΝΟΣ: ΑΝΑΣΤΟΛΕΙΣ ΤΩΝ ΣΗΜΕΙΩΝ ΕΛΕΓΧΟΥ(ΑΝΟΣΟΘΕΡΑΠΕΙΑ)
clinicaloptions.com/oncologyChange Folio Title on Master /Arial 15pt /Unbold Whiteclinicaloptions.com/oncologyClinicalQuiz™: Novel Melanoma Therapies 2015
Tumor Immunology: Overview
Dendritic cell
Perforingranzyme
Cytokines (IL-2)
Activated T cell
T-cell clonal expansion
Resting T cell
Lymph node
TCR CD28
MHCB7
Tumor antigen
1
2
3Tumor
clinicaloptions.com/oncologyChange Folio Title on Master /Arial 15pt /Unbold Whiteclinicaloptions.com/oncologyClinicalQuiz™: Novel Melanoma Therapies 2015
Tumor Immunology: Overview
Dendritic cell
Perforingranzyme
Cytokines (IL-2)
Activated T cell
T-cell clonal expansion
Resting T cell
Lymph node
TCR CD28
MHCB7
Tumor antigen
1
2
3Tumor
clinicaloptions.com/oncologyChange Folio Title on Master /Arial 15pt /Unbold Whiteclinicaloptions.com/oncologyClinicalQuiz™: Novel Melanoma Therapies 2015
Tumor Immunology: Overview
Dendritic cell
Perforingranzyme
Cytokines (IL-2)
Activated T cell
T-cell clonal expansion
Resting T cell
Lymph node
TCR CD28
MHCB7
Tumor antigen
1
2
3Tumor
clinicaloptions.com/oncologyChange Folio Title on Master /Arial 15pt /Unbold Whiteclinicaloptions.com/oncologyClinicalQuiz™: Novel Melanoma Therapies 2015
The T-Cell Dichotomy: Ways to KeepT Cells “Active”
CD28
OX40
GITR
CD137
CD27
HVEM
CTLA-4
PD-1
TIM-3
BTLA
VISTA
LAG-3
Coactivation Signals Inhibitory Signals
T-Cell Stimulation T-Cell Inhibition
T cell
Adapted from Mellman I, et al. Nature. 2011;480:480-489.
Use agonistic mAbs to ↑ activation
Use blocking mAbs to ↑ activation
TCR
clinicaloptions.com/oncologyChange Folio Title on Master /Arial 15pt /Unbold Whiteclinicaloptions.com/oncologyClinicalQuiz™: Novel Melanoma Therapies 2015
PD-1 as a Target in Cancer Therapy
McDermott DF, et al. Cancer Med. 2013;2:662-673.
NivolumabPembrolizumabPidilizumab
Atezolizumab Durvalumab MSB0010718C
PD-L1PD-1
Tumor or APC
CD80CD86CD28
Activated T cellInitial immune
response
CytokinesProliferationActivation
Exhausted T cellPersistent antigen
stimulationCD80CD86
CD28
Tumor or APC
Slide credit: clinicaloptions.com
CheckMate-063: Nivolumab in Previously Treated Squamous NSCLC: Study Design
Planned to treat approximately 100 pts
– Expected ORR of 10% to 50%, with 20% maximum width of exact 2-sided 95% CI
Assessments (RECIST v1.1) performed at Wk 8 and every 6 wks
Primary endpoint: ORR and DoR by IRC (July 2014 database lock)
Secondary endpoint: ORR and DoR by investigator (March 2014 database lock)
Exploratory: safety and tolerability, PFS/OS, PD-L1 expression and efficacy
Stage IIIB/IV squamous NSCLC;
≥ 2 previous systemic
therapies; ECOG PS 0-1
(N = 140)
Nivolumab 3 mg/kg IV Q2W
(n = 117)
Rizvi NA, et al. Lancet Oncol. 2015;16:257-265.
Treatment continued until
progressive disease or
unacceptable toxicity
Slide credit: clinicaloptions.com
CheckMate-063: Overall Survival
Mos
OS
(%)
0
20
40
60
80
100
0 6 12 18 243 9 15 21 27
39%
27%
8.1 mos
41%8.2 mos
Rizvi NA, et al. Lancet Oncol. 2015;16:257-265.Horn L, et al. WCLC 2015. Abstract 828. Slide credit: clinicaloptions.com
Median Follow-up, Mos (Range)
Median OS, Mos (95% CI)
1-Yr OS Rate, % (95% CI)
18-Mo OS Rate, % (95% CI)
Events, n/N
July 2014 8.0 (0-17.3) 8.2
(6.1-10.9) 41 (32-50) – 72/117
June 2015 8.0 (0-26.8) 8.1
(6.1-10.9) 39 (30-48) 27 (19-35) 90/117
CheckMate-063: OS by PD-L1 Expression
Mos
OS
(%)
0 3 6 9 12 15 18 21 24 270
20
40
60
80
100
< 1%≥ 1%Not evaluable
Horn L et al. WCLC 2015. Abstract 828. Slide credit: clinicaloptions.com
Median OS, Mos (95% CI)
Events, n/N
PD-L1 < 1% 8.3 (5.6-15.6) 23/31PD-L1 ≥ 1% 10.1 (5.5-16.8) 32/45Not evaluable 13.0 (1.1-20.8) 8/10
CheckMate-017: Nivolumab vs Docetaxel in Previously Treated Squamous NSCLC Open-label, randomized phase III trial
Primary endpoint: OS
Secondary endpoint: ORR, PFS, associations with PD-L1 expression, QoL
Stage IIIB/IV squamous NSCLC; after failure of
1 previous platinum-based tx; ECOG PS 0-1
(N = 272)
Nivolumab 3 mg/kg IV q2w
(n = 135)
Docetaxel75 mg/m2 IV q3w
(n = 137)
Brahmer J, et al. N Engl J Med. 2015;373:123-135. Slide credit: clinicaloptions.com
100
80
60
40
20
0
CheckMate-017: Overall Survival
0 3 6 9 12 15 18 21 24Mos
OS
(%)
Median OS, Mos (95% CI)9.2 (7.3-13.3)6.0 (5.1-7.3)
NivolumabDocetaxel
HR: 0.59 (95% CI: 0.44-0.79; P < .001)
1-Yr OS, %4224
Brahmer J, et al. N Engl J Med. 2015;373:123-135. Slide credit: clinicaloptions.com
18-Mo OS, %2813
KEYNOTE-001: Pembrolizumab in NSCLC: Subanalysis of Phase I Trial
Administered tumor assessment: imaging every 9 wks
– Primary: Response rate (RECIST)
– Secondary: immune-related response criteria (irRC)
Tumor biopsy
– Tumor biopsy within 60 days prior to first dose of pembrolizumab required
– Tumor PD-L1 expression determined by prototype assay to inform enrollment; samples were independently reanalyzed using clinical trial IHC assay
Garon EB, et al. N Engl J Med. 2015;372:2018-2028.
Treatment-naive or previously treated advanced NSCLC
(N = 495)
Pembrolizumab IV 2 mg/kg q3w (n = 6)
Mandatory tumor biopsy
Pembrolizumab IV 10 mg/kg q3w (n = 287)
Pembrolizumab IV 10 mg/kg q2w (n = 202)
CR, PR, SD
PD, unacceptable AE, or investigator decision
Continue dosing and assessments every 9 wks
Off study
Slide credit: clinicaloptions.com
KEYNOTE-001: Pembrolizumab Efficacy in Overall PopulationORR Pts, n All Cohorts, % (95% CI)Total 495 19.4 (16.0-23.2) Treatment naive 101 24.8 (16.7-34.4) Previously treated 394 18.0 (14.4-22.2) Nonsquamous 401 18.7 (15.0-22.9) Squamous 85 23.5 (15.0-34.0)
Garon EB, et al. N Engl J Med. 2015;372:2018-2028. Slide credit: clinicaloptions.com
KEYNOTE-001: Pembrolizumab Efficacy by PD-L1 Expression
PFS OS100
80
60
40
20
0
PFS
(%)
100
80
60
40
20
0
OS
(%)
0 2 4 6 8 10 12 14 16 18 20 22 24 26Mos
0 4 8 12 16 20 24Mos
28
PS ≥ 50% (n = 119)
PS < 1% (n = 76)PS 1 - 49% (n = 161)
PS ≥ 50% (n = 119)
PS < 1% (n = 76)PS 1 - 49% (n = 161)
ORR Pts, n All Cohorts, % (95% CI)Percent PD-L1 staining
≥ 50% 73 45.2 (33.5-57.3) 1% to 49% 103 16.5 (9.9-25.1) < 1% 28 10.7 (2.3-28.2)
Garon EB, et al. N Engl J Med. 2015;372:2018-2028. Slide credit: clinicaloptions.com
KEYNOTE-010: Pembrolizumab vs Doc in Previously Treated PD-L1+ NSCLC
End points in the TPS ≥ 50% stratum and TPS ≥ 1% population Primary: PFS and OS Secondary: ORR, DoR, safety
Advanced NSCLC; confirmed PD after ≥ 1 line of
chemotherapy; no active brain metastases; ECOG PS 0-1; PD-L1 TPS ≥ 1%; no serious autoimmune disease; no ILD
or pneumonitis requiring systemic steroids
(N = 1034)
Pembrolizumab 10 mg/kg IV q3w/24 mos
(n = 346)
Docetaxel 75 mg/m2 IV q3w(n = 343)
Stratified by ECOG PS (0 vs 1); region (East Asia vs non-East Asia); PD-L1
status (TPS ≥50% vs 1%-49%)
Herbst RS, et al. Lancet. 2015;[Epub ahead of print].
Phase II Study
Pembrolizumab 2 mg/kg IV q3w/24 mos
(n = 345)
Slide credit: clinicaloptions.com
KEYNOTE-010: Overall Survival
Total Pt Population Pts With PD-L1 TPS ≥ 50%*
Herbst RS, et al. Lancet. 2015;[Epub ahead of print].
Mos
Slide credit: clinicaloptions.com
100
80
60
40
20
00 5 10 15 20 25
OS
(%)
Pembrolizumab 2 mg/kgPembrolizumab 10 mg/kgDocetaxel
Mos
100
80
60
40
20
00 5 10 15 20 25
OS
(%)
Pembrolizumab 2 mg/kgPembrolizumab 10 mg/kgDocetaxel
*Treatment Arm Median, mo (95% CI) HR (95% CI) PPembro 2 mg/kg 14.9 (10.4-NR) 0.54 (0.38-0.77) .0002Pembro 10 mg/kg 17.3 (11.8-NR) 0.50 (0.36-0.70) < .0001Docetaxel 8.2 (6.4-10.7) — —
POPLAR: Atezolizumab vs Docetaxel in Previously Treated NSCLC
Primary endpoint: OS in PD-L1–selected and ITT populations Secondary endpoints: overall safety as well as PFS, ORR, DoR in PD-L1–
selected and ITT populations
Pts with locally advanced or metastatic NSCLC and ECOG
PS 0-1 who failed prior platinum-containing
chemotherapy(N = 287)
Atezolizumab 1200 mg IV q3w(n = 144)
Docetaxel 75 mg/m2 IV q3w(n = 143)
Stratified by PD-L1 immune cell expression (0 vs 1 vs 2 vs 3), histology (squamous vs nonsquamous),
and line of therapy (second vs third line)
Spira AI, et al. ASCO 2015. Abstract 8010.
Phase II Study
Slide credit: clinicaloptions.com
POPLAR: OS by Histology
Event/pt ratio:
– Squamous 69% (63% for atezolizumab, 75% for docetaxel)
– Nonsquamous 56% (49% for atezolizumab, 62% for docetaxel)Vansteenkiste J, et al. ESMO 2015. Abstract LBA14. Slide credit: clinicaloptions.com
10.1 (6.7-14.5)
15.5 (9.8-NE)
12.6 (9.7-16.4)
8.6 (5.4-11.6)
10.9 (8.8-13.6)
9.7 (8.6-12.0)
Atezolizumab DocetaxelMedian OS, Mos (95% CI)
Squamous
Nonsquamous
ITT
97 (34)
190 (66)
N = 287
Subgroup n (%)
0.2 1 2
0.69
0.80
0.73
Favors atezolizumab Favors docetaxel
HR*
*Unstratified HR for subgroups and stratified HR for ITT. Data cutoff May 8, 2015.
ΣΥΜΠΕΡΑΣΜΑΤΑ Η ΠΡΩΤΗΣ ΓΡΑΜΜΗΣ ΘΕΡΑΠΕΙΑ ΜΕ ΔΙΠΛΕΤΑ ΠΛΑΤΙΝΑΣ
ΠΑΡΑΜΕΝΕΙ Η ΚΑΘΙΕΡΩΜΕΝΗ ΘΕΡΑΠΕΙΑ ΓΙΑ ΤΟ ΠΛΑΚΩΔΕΣ CA ΠΝΕΥΜΟΝΟΣ
ΟΙ ΑΝΑΣΤΟΛΕΙΣ ΤΩΝ ΣΗΜΕΙΩΝ ΕΛΕΓΧΟΥ ΤΗΣ ΑΝΟΣΙΑΣ ΕΙΝΑΙ ΕΓΚΕΚΡΙΜΕΝΟΙ ΩΣ ΔΕΥΤΕΡΗ ΓΡΑΜΜΗ ΘΕΡΑΠΕΙΑΣ: ΤΟ NIVOLUMAB ΣΕ ΜΗ ΕΠΙΛΕΓΜΕΝΟΥΣ ΑΣΘΕΝΕΙΣ, ΚΑΙ ΤΟ PEMBROLIZUMAB ΣΕ ΑΣΘΕΝΕΙΣ ΜΕ ΟΓΚΟΥΣ ΘΕΤΙΚΟΥΣ ΓΙΑ ΕΚΦΡΑΣΗ PD-1.
ΤΟ DOCETAXEL ΣΕ ΣΥΝΔΥΑΣΜΟ ΜΕ RAMUCIRUMAB ΕΙΝΑΙ ΜΙΑ ΛΟΓΙΚΗ ΕΠΙΛΟΓΗ ΔΕΥΤΕΡΗΣ ΓΡΑΜΜΗΣ ΘΕΡΑΠΕΙΑΣ.
ΟΙ ΑΝΑΣΤΟΛΕΙΣ TKI ΤΟΥ EGFR EXOYN ΠΕΡΙΟΡΙΣΜΕΝΟ ΡΟΛΟ ΣΕ ΑΥΤΟΥΣ ΤΟΥΣ ΑΣΘΕΝΕΙΣ.
ΝΕΟΙ ΣΤΟΧΟΙ ΘΕΡΑΠΕΙΑΣ ΑΚΟΜΗ ΕΙΝΑΙ ΑΝΑΓΚΑΙΟΙ.
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