4. 15% of lung cancer
Central mass
Very-early systemic
spread
Higher letality
Tobacco explains
about 99%
Limited-stage
(confined to one
lung)
Extensive-stage
(beyond one lung)
Very high CNS
involvement
SCLC
https://www.youtube.com/watch?v=nQQFDvQqw9A
Neuroendocrine,
small cell
Chromogranin
Synaptophysin
5. Hitos Históricos en SCLC (1/3)
Tabaco
Aborígenes a C. Colón
Tabaco
en
Europa
Análisis
de
Estputo
Broncosco
pia
Killian
Lobectomí
a
Morriston-Davies
Ca
pulmón
Laennec
Radón
Cáncer de pulmón
enmineros de uranio
expuestos a radón
Rayos X
Röntgen
Células en
Avena
Barnard
1492
1500
1815
1821
1878
1895
1895
1913
1926
6. SCLC
Small Cell Lung Cancer
El tumor está compuesto por una proliferación difusa de células de
tamaño pequeño a intermedio (flecha), generalmente con un
citoplasma muy escaso y núcleos hipercromáticos redondos a
ovalados. Las células tumorales son generalmente más grandes que
los linfocitos pequeños (punta de flecha izquierda) pero en algunos
casos la distinción morfológica puede ser imposible.
7. Hitos Históricos en SCLC (1/3)
Tabaco
Aborígenes a C. Colón
Tabaco
en
Europa
Análisis
de
Estputo
Broncosco
pia
Killian
Lobectomí
a
Morriston-Davies
Pneumonecto
mía
Graham
Ca
pulmón
Laennec
Radón
Cáncer de pulmón
enmineros de uranio
expuestos a radón
Rayos X
Röntgen
Células en
Avena
Barnard
Mostaza
nitrogenada
Inicio de quimioterapia
1492
1500
1815
1821
1878
1895
1895
1913
1926
1933
1942
8. Hitos Históricos en SCLC (2/3)
Tabaco/cánce
r
Doll-Hill
Distinció
n SCLC /
NSCLC
LD vs ED
por
VALCSG
Patología
SCLC
Azzopardi
1950
1959
1959
1968
9.
10. Hitos Históricos en SCLC (2/3)
Tabaco/cánce
r
Doll-Hill
Distinció
n SCLC /
NSCLC
LD vs ED
por
VALCSG
RT major que
cirugía
MRC
Poliquimio
Con alta tasa de respuesta
EP
Estándar
Patología
SCLC
Azzopardi
Ciclofosfamid
a
Autopsias
SCLC
-
Diseminado
s -
Ciclofosfamida
RT superior a
RT
RT + EP
Superior a EP en LD
1950
1959
1959
1968
1969
1969
1973
1970
1979
1980
1987
11. Small-Cell Lung Cancer
SCLC
Stage I All others
Confirmed Stage I
Surgery + EP
Limited-Stage Extended-stage
EP + RT Platin + E
EP: Etoposide + Cisplatin x4 months
70% LT survival
13. Small-Cell Lung Cancer
SCLC
Stage I All others
Confirmed Stage I
Surgery + EP
Limited-Stage Extended-stage
EP + RT + PCI Platin + E +/- PCI
EP: Etoposide + Cisplatin x4 months
PCI: Prophylactic Cranial Irradiation
70% LT survival Median OS: 20 months Median OS: 9 months
15. Permite el paso de G1 a S (proliferación
cellular)
Permite la proliferación de células
defectuosas
Multiplica la proliferación
Anormalidades genómicas recurrentes SCLC
RB1 p53
Myc Inestabilidad
genómica
Alta carga
mutacional
18. How to handle small tissue samples in lung cancer
p63 and TTF1
H&E
Squamous Non-squamous
Genomics
SCLC
NeuroEndocrine EGFR
ALK/EML4
ROS1
BRAF
Her2
p63+ TTF1+
PD-L1 by IHC
(in advanced NSCLC)
PD-L1 by IHC
(in advanced NSCLC)
Chromogranin
Synaptophysin
20. Investigación
Diseminación pulmonar, mediastinal, pleural, ósea, hepatica, Sistema nervioso central
TAC / PET-
CT
Considerar
biopsia de
médula
ósea
RM de cráneo
Biopsia en mediastino
Si se considera que va a ser
candidato a cirugía
22. 8th Edition of the TNM Classification
for Lung Cancer
N0 N1 N2 N3 M1a M1b M1c
T1a IA1 IIB IIIA IIIB IVA IVA IVB
T1b IA2 IIB IIIA IIIB IVA IVA IVB
T1c IA3 IIB IIIA IIIB IVA IVA IVB
T2a IB IIB IIIA IIIB IVA IVA IVB
T2b IIA IIB IIIA IIIB IVA IVA IVB
T3 IIB IIIA IIIB IIIC IVA IVA IVB
T4 IIIA IIIA IIIB IIIC IVA IVA IVB
International Association for the Study of Lung Cancer, 2015
Investigación: PET-CT / RM de cráneo / Evaluación mediastinal histológica
Lobectomía más disección ganglionar – más quimioterapia +/- RT
23. 8th Edition of the TNM Classification
for Lung Cancer
N0 N1 N2 N3 M1a M1b M1c
T1a IA1 IIB IIIA IIIB IVA IVA IVB
T1b IA2 IIB IIIA IIIB IVA IVA IVB
T1c IA3 IIB IIIA IIIB IVA IVA IVB
T2a IB IIB IIIA IIIB IVA IVA IVB
T2b IIA IIB IIIA IIIB IVA IVA IVB
T3 IIB IIIA IIIB IIIC IVA IVA IVB
T4 IIIA IIIA IIIB IIIC IVA IVA IVB
International Association for the Study of Lung Cancer, 2015
Investigación: PET-CT / RM de cráneo
Quimiorradioterapia concomitante con EP + Irradiación Cranial profiláctica
24. 8th Edition of the TNM Classification
for Lung Cancer
N0 N1 N2 N3 M1a M1b M1c
T1a IA1 IIB IIIA IIIB IVA IVA IVB
T1b IA2 IIB IIIA IIIB IVA IVA IVB
T1c IA3 IIB IIIA IIIB IVA IVA IVB
T2a IB IIB IIIA IIIB IVA IVA IVB
T2b IIA IIB IIIA IIIB IVA IVA IVB
T3 IIB IIIA IIIB IIIC IVA IVA IVB
T4 IIIA IIIA IIIB IIIC IVA IVA IVB
International Association for the Study of Lung Cancer, 2015
Systemic therapy
25. Small-Cell Lung Cancer
SCLC
Stage I-IIA All others
Surgery
EP +/-RT
IIB-IIIC IV
EP + RT + PCI Platin + E +/- PCI
EP: Etoposide + Cisplatin x4 months
PCI: Prophylactic Cranial Irradiation
70% LT survival Median OS: 20 months Median OS: 9 months
26. Hitos Históricos en SCLC (3/3)
Irradiación
cranial
profiláctica
RT dos
veces
por día
Hedge-
Hogg
CASPIAN
Durvalumab
Vías
moleculares
IMpower133
1995
1999
2000
2006
2018
2019
2020
Lurbinectedina
28. CASPIAN: Phase III Study of First-line Durvalumab +
Tremelimumab + EP vs Durvalumab + EP vs EP
Alone in Extensive-Stage SCLC
This activity is provided by Clinical Care Options, LLC
Supported by educational grants from AstraZeneca; Daiichi Sankyo, Inc.;
Ipsen Pharma; Jazz Pharmaceuticals, Inc.; and Merck Sharp & Dohme Corp.
CCO Independent Conference Coverage*
Highlights of the 2020 ASCO Virtual Scientific Meeting, May 29-31, 2020
*CCO is an independent medical education company that provides state-of-the-art medical information to
healthcare professionals through conference coverage and other educational programs.
29. CASPIAN: Study Design
Randomized, open-label, multicenter phase III study
Primary endpoint: OS
Secondary endpoints: PFS and ORR (investigator-assessed per RECIST v1.1), safety and
tolerability, PROs
Treatment-naive, extensive-stage
SCLC, WHO PS 0/1, measurable
disease per RECIST v1.1, life
expectancy ≥ 12 wks,
asymptomatic or treated and
stable brain metastases
(N = 805)
Durvalumab + Tremelimumab + EP*
Q3W x 4 cycles
(n = 268)
EP*
Q3W x 4-6 cycles†
(n = 269)
Durvalumab + EP*
Q3W x 4 cycles
(n = 268)
*Etoposide 80-100 mg/m2 with either carboplatin AUC 5-6 or cisplatin 75-80 mg/m2,
durvalumab 1500 mg, tremelimumab 75 mg.
†Per investigator discretion, additional 2 cycles of EP (6 cycles total) and PCI
Progressive
Disease
Slide credit: clinicaloptions.com
Durvalumab
Q4W
Optional PCI†
Durvalumab
Q4W
Stratified by planned carboplatin vs cisplatin
Paz-Ares. ASCO 2020. Abstr 9002.
31. CASPIAN: OS for Durvalumab + Tremelimumab + EP
vs EP
Paz-Ares. ASCO 2020. Abstr 9002. Reproduced with permission. Slide credit: clinicaloptions.com
*P ≤ .0418 required for statistical significance
Durvalumab + Tremelimumab + EP
(n = 268)
EP
(n = 269)
Events, n (%) 207 (77.2) 231 (85.9)
Median OS, mos (95% CI) 10.4 (9.6-12.0) 10.5 (9.3-11.2)
HR (95% CI) 0.82 (0.68-1.00); P = .0451*
Mos
Probability
of
OS
1.0
0.8
0.6
0.4
0.2
0
36
0 3 6 9 12 15 18 21 24 27 30 33
43.8%
39.3%
24.8%
14.4%
30.7%
23.4%
No. at risk
D+T+EP
EP
268
269
238
243
200
212
156
156
114
104
92
82
80
64
67
48
47
24
30
8
11
0
1
0
0
0
32. CASPIAN: Subgroup OS Analysis for Durvalumab +
Tremelimumab + EP vs EP
Paz-Ares. ASCO 2020. Abstr 9002. Reproduced with permission. Slide credit: clinicaloptions.com
*Post hoc analysis; all other subgroups were prespecified
Favors D+T+EP Favors EP
0.25 0.5 1 2
HR (95% CI)
0.82 (0.68-1.00)
0.84 (0.67-1.04)
0.79 (0.55-1.15)
0.76 (0.59-0.97)
0.92 (0.69-1.22)
0.83 (0.66-1.03)
0.76 (0.52-1.10)
0.79 (0.58-1.09)
0.87 (0.69-1.10)
0.86 (0.70-1.04)
0.43 (0.17-1.02)
0.91 (0.53-1.59)
0.81 (0.66-0.98)
0.90 (0.68-1.20)
0.74 (0.58-0.96)
0.96 (0.47-1.88)
0.81 (0.67-0.99)
0.86 (0.53-1.38)
0.81 (0.66-1.00)
0.90 (0.55-1.46)
0.78 (0.62-0.96)
1.08 (0.58-2.03)
All patients (n = 537)
Planned platinum agent
Age
Sex
Performance status
Smoking status
Brian/CNS metastases
Liver metastases*
AJCC disease stage at diagnosis
Race
Region
Carboplatin (n = 401)
Cisplatin (n = 136)
< 65 years (n = 311)
≥ 65 years (n = 226)
Male (n = 386)
Female (n = 151)
0 (n = 199)
1 (n = 338)
Smoker (n = 507)
Non-smoker (n = 30)
Yes (n = 65)
No (n = 472)
Yes (n = 221)
No (n = 316)
Stage III (n = 42)
Stage IV (n = 495)
Asian (n = 89)
Non-Asian (n = 447)
Asia (n = 84)
Europe (n = 404)
North and South America (n = 49)
33. CASPIAN: PFS and Confirmed Objective Response for
Durvalumab + Tremelimumab + EP vs EP
Slide credit: clinicaloptions.com
D + T + EP
(n = 268)
EP
(n = 269)
Events, n (%) 229 (85.4) 236 (87.7)
Median PFS, mos
(95% CI)
4.9 (4.7-5.9) 5.4 (4.8-6.2)
HR (95% CI) 0.84 (0.70-1.01)
D + T + EP
(n = 268)
EP
(n = 269)
ORR, n (%) 156 (58.4*) 156 (58.0)
Median DOR,
mos (95% CI)
5.2 (4.9-5.6) 5.1 (4.8-5.3)
*1 patient had no measurable disease at baseline.
Paz-Ares. ASCO 2020. Abstr 9002. Reproduced with permission.
PFS Duration of Response
1.0
0.8
0.6
0.4
0.2
0
Probability
of
PFS
Mos
33
0 3 6 9 12 15 18 21 24 27 30
No. at risk
D+T+EP
EP
268
269
204
195
111
110
54
33
42
12
36
9
30
7
26
7
18
6
5
1
1
0
0
0
16.9% 11.5%
2.9%
5.3%
1.0
0.8
0.6
0.4
0.2
0
Probability
of
PFS
Mos
33
0 3 6 9 12 15 18 21 24 27 30
No. at risk
D+T+EP
EP
156
156
146
145
61
50
41
17
37
10
31
6
26
6
21
4
10
4
4
0
1
0
0
0
24.9%
17.2%
3.9%
7.3%
34. CASPIAN: OS for Durvalumab + EP vs EP
Slide credit: clinicaloptions.com
Durvalumab + EP
(n = 268)
EP
(n = 269)
Events, n (%) 210 (78.4) 231 (85.9)
Median OS, mos (95% CI) 12.9 (11.3-14.7) 10.5 (9.3-11.2)
HR (95% CI) 0.75 (0.62-0.91); P = .0032
Paz-Ares. ASCO 2020. Abstr 9002. Reproduced with permission.
Mos
Probability
of
OS
1.0
0.8
0.6
0.4
0.2
0
36
0 3 6 9 12 15 18 21 24 27 30 33
52.8%
39.3%
24.8%
14.4%
32.0%
22.2%
No. at risk
D+EP
EP
268
269
244
243
214
212
177
156
140
104
109
82
85
64
66
48
41
24
21
8
8
0
2
0
0
0
35. CASPIAN: Subgroup OS Analysis for
Durvalumab + EP vs EP
Slide credit: clinicaloptions.com
*Post hoc analysis; all other subgroups were prespecified
Paz-Ares. ASCO 2020. Abstr 9002. Reproduced with permission.
Favors D+EP Favors EP
0.5 1 2
HR (95% CI)
0.75 (0.62-0.91)
0.79 (0.63-0.98)
0.67 (0.46-0.97)
0.72 (0.56-0.91)
0.84 (0.62-1.12)
0.79 (0.63-0.99)
0.65 (0.45-0.93)
0.77 (0.56-1.06)
0.76 (0.60-0.96)
0.75 (0.62-0.91)
0.83 (0.41-1.71)
0.79 (0.44-1.41)
0.76 (0.62-0.92)
0.87 (0.66-1.16)
0.68 (0.53-0.88)
0.83 (0.44-1.54)
0.75 (0.62-0.92)
0.86 (0.52-1.40)
0.75 (0.61-0.92)
0.87 (0.53-1.43)
0.74 (0.60-0.92)
0.77 (0.42-1.43)
All patients (n = 537)
Planned platinum agent
Age
Sex
Performance status
Smoking status
Brian/CNS metastases
Liver metastases*
AJCC disease stage at diagnosis
Race
Region
Carboplatin (n = 402)
Cisplatin (n = 135)
< 65 years (n = 324)
≥ 65 years (n = 213)
Male (n = 374)
Female (n = 163)
0 (n = 189)
1 (n = 348)
Smoker (n = 500)
Non-smoker (n = 37)
Yes (n = 55)
No (n = 482)
Yes (n = 212)
No (n = 325)
Stage III (n = 52)
Stage IV (n = 485)
Asian (n = 78)
Non-Asian (n = 458)
Asia (n = 76)
Europe (n = 405)
North and South America (n = 56)
36. CASPIAN: PFS for Durvalumab + EP vs EP
PFS not formally tested for statistical significance
56.8% in control arm received 6 cycles EP
Slide credit: clinicaloptions.com
D + EP
(n = 268)
EP
(n = 269)
Events, n (%) 234 (87.3) 236 (87.7)
Median PFS, mos
(95% CI)
5.1 (4.7-6.2) 5.4 (4.8-6.2)
HR (95% CI) 0.80 (0.66-0.96)
Landmark
PFS, %
D + EP
(n = 268)
EP
(n = 269)
6 mos 45.4 45.8
12 mos 17.9 5.3
18 mos 13.9 3.4
24 mos 11.0 2.9
Paz-Ares. ASCO 2020. Abstr 9002. Reproduced with permission.
1.0
0.8
0.6
0.4
0.2
0
Probability
of
PFS
Mos
33
0 3 6 9 12 15 18 21 24 27 30
No. at risk
D+EP
EP
268
269
220
195
119
110
55
33
45
12
40
9
35
7
24
7
18
6
8
1
5
0
0
0
17.9% 11.0%
2.9%
5.3%
37. CASPIAN: Confirmed Objective Response for Durvalumab
+ EP vs EP
Slide credit: clinicaloptions.com
D + EP
(n = 268)
EP
(n = 269)
Responders, n 182 156
Median DoR, mos
(95% CI)
5.1 (4.9-5.3) 5.1 (4.8-5.3)
Paz-Ares. ASCO 2020. Abstr 9002. Reproduced with permission.
1.0
0.8
0.6
0.4
0.2
0
Probability
of
patients
in
response
Time from confirmed objective response (months)
33
0 3 6 9 12 15 18 21 24 27 30
No. at risk
D+EP
EP
182
156
170
145
70
50
45
17
40
10
35
6
27
6
17
4
12
4
6
0
0
0
0
0
23.2%
13.5%
3.9%
7.3%
Duration of Response
ORR
100
EP
(n = 269)
D+EP
(n = 268)
80
60
40
20
0
Patients
with
response,
%
Odds ratio: 1.53
(95% CI: 1.08-2.18)
67.9
58.0
38. 23.4%
22.2%
CASPIAN: OS in All Arms
Paz-Ares. ASCO 2020. Abstr 9002.
Mos
Probability
of
OS
1.0
0.8
0.6
0.4
0.2
0
36
0 3 6 9 12 15 18 21 24 27 30 33
32.0%
30.7%
24.8%
D+T+EP
D+EP
EP
268
268
269
238
244
243
200
214
212
156
177
156
114
140
104
92
109
82
80
85
64
67
66
48
47
41
24
30
21
8
11
8
0
1
2
0
0
0
0
14.4%
Median follow-up in censored patients: 25.1 mos (range: 0.1-33.7).
Patient at Risk, n
D+T+EP
D+EP
EP
Slide credit: clinicaloptions.com
39. CASPIAN: Safety
Paz-Ares. ASCO 2020. Abstr 9002. Slide credit: clinicaloptions.com
AEs, n (%)
Durvalumab + Tremelimumab + EP
(n = 266)
Durvalumab + EP
(n = 265)
EP
(n = 266)
Any grade, all-cause AEs 246 (99.2) 260 (98.1) 258 (97.0)
Grade 3/4 AEs 187 (70.3) 165 (62.3) 167 (62.8)
Serious AEs 121 (45.5) 85 (32.1) 97 (36.5)
AEs leading to d/c* 57 (21.4) 27 (10.2) 25 (9.4)
Immune-mediated AEs† 96 (36.1) 53 (20.0) 7 (2.6)
AEs leading to death
Treatment-related‡
27 (10.2)
12 (4.5)
13 (4.9)
6 (2.3)
15 (5.6)
2 (0.8)
*Includes d/c of at least 1 study drug.
†Any event consistent with immune-mediated MOA with no clear alternate etiology that required systemic treatment; majority
were thyroid related and low grade.
‡Investigator assessed as possibly related to study drug(s).
40. Conclusions
First-line durvalumab + EP demonstrated ongoing improvement of OS vs EP in patients
with extensive-stage SCLC
‒ HR: 0.75 (95% CI: 0.62-0.91; P = .0032)
‒ At 24 mos, 22.2% of patients receiving durvalumab + EP remained alive vs 14.4% with EP
‒ OS benefit preserved across prespecified subgroups; benefit observed in key secondary
outcomes
No significant improvement in outcomes with addition of tremelimumab to
durvalumab + EP
Safety outcomes consistent with known safety profiles of each agent
Investigators conclude durvalumab + EP should be considered a new standard of care
for first-line therapy in patients with extensive-stage SCLC
Paz-Ares. ASCO 2020. Abstr 9002. Slide credit: clinicaloptions.com
41. IMpower133: Addition of Atezolizumab to
First-line Carboplatin/Etoposide in
Extensive-Stage Small-Cell Lung Cancer
Supported by educational grants from AbbVie, AstraZeneca, Genentech, and Takeda Oncology.
Building a Bridge Between Science and Practice:
CCO Independent Conference Highlights*
from the 19th World Conference on Lung Cancer;
September 23-26, 2018; Toronto, Canada
*CCO is an independent medical education company that provides state-of-the-art medical information to
healthcare professionals through conference coverage and other educational programs.
42. Atezolizumab in ES-SCLC: Background
Little progress in first-line treatment of ES-SCLC in past 20 yrs
‒ Standard of care remains platinum (carboplatin or cisplatin) plus etoposide[1-3]
‒ Patient outcomes remain poor, with a median OS of about 10 mos[3,4]
Immune checkpoint inhibitors have shown clinical activity in refractory or
metastatic SCLC[5-6]
‒ Nivolumab monotherapy approved as third-line treatment of metastatic SCLC[7]
‒ Preclinical data suggest possible synergy between anti–PD-L1 treatment and
chemotherapy[8]
IMpower133 evaluated the efficacy and safety of first-line atezolizumab (an
anti–PD-L1 antibody) or placebo in combination with carboplatin and etoposide
in ES-SCLC[9,10]
References in slidenotes. Slide credit: clinicaloptions.com
43. IMpower133: Phase I/III Study of First-line Atezolizumab
Plus Carboplatin/Etoposide in ES-SCLC
Patients with ES-SCLC,
ECOG PS 0/1, no prior
systemic therapy for
ES-SCLC
(N = 403)
Treatment until
PD or loss of
clinical benefit
Atezolizumab 1200 mg on Day 1
Carboplatin AUC 5 on Day 1
Etoposide 100 mg/m2 on Days 1-3
4 x 21-day cycles
(n = 201)
Placebo
Carboplatin AUC 5 on Day 1
Etoposide 100 mg/m2 on Days 1-3
4 x 21-day cycles
(n = 202)
Slide credit: clinicaloptions.com
Stratified by treated asymptomatic brain metastases
(yes vs no), sex (male vs female), ECOG PS (0 vs 1)
Atezolizumab
Placebo
Induction Maintenance
Co-primary endpoints: investigator-assessed PFS, OS
Secondary endpoints: ORR, DoR, safety
Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print].
Randomized, double-blind, placebo-controlled phase I/III trial
44. IMpower133: Baseline Patient Characteristics
Characteristic
Atezolizumab + Carboplatin/Etoposide
(n = 201)
Placebo +
Carboplatin/Etoposide
(n = 202)
Median age, yrs (range) 64 (28-90) 64 (26-87)
< 65 yrs, n (%) 111 (55) 106 (52)
≥ 65 yrs, n (%) 90 (45) 96 (48)
Male, n (%) 129 (64) 132 (65)
White, n (%) 163 (81) 159 (79)
Asian, n (%) 33 (16) 36 (18)
ECOG PS 0, n (%) 73 (36) 67 (33)
ECOG PS 1, n (%) 128 (64) 135 (67)
Current smoker, n (%) 74 (36.8) 75 (37.1)
Former smoker, n (%) 118 (58.7) 126 (61.4)
Brain metastases, n (%) 17 (8) 18 (9)
Liver metastases, n (%) 77 (38) 72 (36)
Slide credit: clinicaloptions.com
Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print].
45. IMpower133: OS
Slide credit: clinicaloptions.com
Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print].
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Mos
100
80
60
40
20
0
OS
(%)
12-month OS
51.7%
38.2%
12-mo OS
Atezolizumab
+ CP/ET
(n = 201)
Placebo
+ CP/ET
(n = 202)
Median OS, mos (95% CI) 12.3 (10.8-15.9) 10.3 (9.3-11.3)
HR (95% CI) 0.70 (0.54-0.91); P = .0069
Median follow-up, mos 13.9
Atezolizumab + CP/ET
Placebo + CP/ET
46. IMpower133: PFS (Investigator Assessed)
Slide credit: clinicaloptions.com
Liu SV, et al. WCLC 2018. Abstract PL02.07. Horn L, et al. N Engl J Med. 2018;379:[Epub ahead of print].
Atezolizumab
+ CP/ET
(n = 201)
Placebo
+ CP/ET
(n = 202)
Median PFS, mos (95% CI) 5.2 (4.4-5.6) 4.3 (4.2-4.5)
HR (95% CI) 0.77 (0.62-0.96); P = .017
Median follow-up, mos 13.9
Atezolizumab + CP/ET
Placebo + CP/ET
6-mo PFS
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
100
80
60
40
20
0
12-mo PFS
30.9%
22.4%
5.4%
12.6%
PFS
(%)
Mos
51. IMpower133: Conclusions
Slide credit: clinicaloptions.com
References in slidenotes.
First-line therapy with atezolizumab + carboplatin/etoposide significantly improved OS and
PFS vs carboplatin/etoposide alone[1,2]
‒ Median OS: 12.3 vs. 10.3 mos; HR: 0.70 (P = .0069); 12-mo OS rate: 51.7% vs. 38.2%
‒ Median PFS: 5.2 vs. 4.3 mos; HR: 0.77 (P = .017); 12-mo PFS rate: 12.6% vs. 5.4%
No unexpected safety signals were reported
‒ Similar rates of hematologic AEs between treatment groups
‒ Chemotherapy delivery was not different between treatment groups
‒ irAE incidence and types were similar to those seen with atezolizumab monotherapy[3-5]
The investigators suggest that atezolizumab + carboplatin/etoposide is a new standard of
care for the first-line treatment of ES-SCLC[1,2]