Dr. Delvys Rodríguez
Día 3
Inmunoterapia en cáncer de pulmón metastásico
5y OS 23%5y OS 15%
Late Toxicities
5-Year OS from KEYNOTE-001
Lung MAP: Nivo vs Nivo/Ipi previously treated squamous
IMpower150: Analysis of Effica c y in Patients With Liver MetastasesMark A. Socinski,1 Robert Jotte,2 Federico Cappuzzo,3 Tony Mok,4 Howard West,5 Makota Nishio,6 Vassiliki A. Papadimitrakopoulou,7 Francisco Orlandi,8 Daniil Stroyakovskiy,9 Christian A. Thomas,10 Naoyuki Nogami,11 Fabrice Barlesi,12 Anthony Lee,13 Geetha Shankar,13 Wei Yu,13 Marcus Ballinger,13 Ilze Bara,13 Alan Sandler,13 Martin Reck14
1AdventHealth Cancer Institute, Orlando, FL; 2Rocky Mountain Cancer Centers, Denver, CO; 3Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy; 4Chinese University of Hong Kong, Hong Kong, China; 5Swedish Cancer Institute, Seattle, WA; 6The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; 7The University of Texas MD Anderson Cancer Center, Houston, TX; 8Instituto Nacional del Torax, Santiago, Chile; 9Moscow City Oncology Hospital, Moscow, Russia; 10New England Cancer Specialists, Scarborough, ME; 11National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan; 12Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France;
13Genentech, Inc., South San Francisco, CA; 14Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany
BACKGROUNDNSCLC and Liver Metastases
• For patients with advanced non-small cell lung cancer (NSCLC), recommended firs t-line treatments include:1,2
- Tyrosine kinase inhibitors for patients with oncogenic alterations (e.g., EGFR mutations or ALK translocations)
- Pembrolizumab (anti–programmed death-1 [PD-1]) monotherapy for patients with high programmed
death-ligand 1 (PD-L1)–expressing tumors (tumor proportion score ≥ 50%)
- Platinum-based chemotherapy alone or with bevacizumab,3 pembrolizumab4 or atezolizumab + bevacizumab
• Tumor metastases to the liver are common in patients with lung cancer and are associated with a poorer
prognosis compared with metastases to other sites.5 Additionally, the presence of liver metastases may
signal a high tumor burden, and VEGF activation may play a role at specific
organs/sites6,7
• Patients with liver metastases experience limited benefit
with anti–PD-L1 or anti–PD-1 monotherapies6,8,9
• Combination regimens of checkpoint inhibitors with nab-paclitaxel have also shown limited effic
a
cy in
this population10
• Thus, additional treatment options are needed for these patients
Combining Atezolizumab + Bevacizumab + Chemotherapy
• Atezolizumab is a monoclonal anti≥PD-L1 antibody that inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, thus restoring tumor-specific
immunity11,12
• Atezolizumab, as monotherapy and in combination with chemotherapy, has shown effica cy in patients
with NSCLC13,14
• Bevacizumab, a recombinant humanized VEGF monoclonal antibody, combined with chemotherapy
had a signific
a
ntly better outcome for overall survival (OS) than chemotherapy alone in patients with
advanced NSCLC in a Phase II/III study (E4599; NCT00021060)3
• In a subpopulation of patients with baseline liver metastases in E4599, the combination of bevacizumab plus chemotherapy demonstrated improved OS vs chemotherapy alone (Figure 1)
Figure 1. Bevacizumab With Chemotherapy Demonstrated OS Benefit
vs Chemotherapy
Alone in Patients With Baseline Liver Metastases (historical data from E4599)
BCP, bevacizumab + carboplatin + paclitaxel; CP, carboplatin + paclitaxel; HR, hazard ratio.
• In combination with bevacizumab and chemotherapy, atezolizumab’s T-cell–mediated cancer cell killing
may be further enhanced through both reversal of VEGF-mediated immunosuppression15 and
chemotherapy-induced cell death16 (Figure 2)
Figure 2. Rationale for the Combination of Atezolizumab With Bevacizumab and Chemotherapy
DC, dendritic cell; MDSC, myeloid-derived suppressor cell; Treg, regulatory T cell.
• The randomized Phase III IMpower150 study demonstrated statistically significant and clinically meaningful improvements with atezolizumab + bevacizumab + chemotherapy vs bevacizumab +
chemotherapy in progression-free survival (PFS; HR, 0.62 [95% CI: 0.52, 0.74]; p < 0.001) and
OS (HR, 0.78 [95% CI: 0.64, 0.96]; p = 0.02)17
• Notably, the combination of atezolizumab + bevacizumab + chemotherapy showed clinical benefit in the subgroup of patients with baseline liver metastases compared with the combination of
bevacizumab + chemotherapy18
• The objective of this exploratory analysis was to further evaluate the subgroup of patients with baseline
liver metastases treated with atezolizumab + bevacizumab + chemotherapy in the IMpower150 study,
including baseline characteristics, effic
a
cy and safety
100
90
80
70
Overa
ll S
urviva
l (%
)
Months
60
50
40
30
20
10
0
0
93
CP
BCP 71 49 31 15 6 5 1 1
74 49 21 13 7 3 2 1 0
5 10 15 20 25 30 35 40
HR, 0.68
(95% CI: 0.49, 0.96)
No. at risk
Tumor cells
Dendritic cell
Activated T cells
Tumor antigens
ChemotherapyPromotes recruitment of DCs to the
site of cell death16
Atezolizumab Restores anti-cancer immunity,11,12
with activity further enhanced through
VEGF-mediated immunomodulatory
effects and chemotherapy-induced
tumor antigen exposure
Bevacizumab Normalizes the tumor vasculature, increasing T-cell infiltration12
Bevacizumab Decreases the activity of
immunosuppressive cells
(MDSCs and Tregs)12
Bevacizumab Promotes DC maturation12
AtezolizumabPromotes T-cell activation by allowing
B7.1 co-stimulation11,12
METHODSStudy Design and Patient Population
• IMpower150 (NCT02366143) is a randomized, open-label, international, Phase III study designed to evaluate the effic
a
cy and safety of atezolizumab + carboplatin + paclitaxel (ACP) or atezolizumab +
bevacizumab + carboplatin + paclitaxel (ABCP) vs bevacizumab + carboplatin + paclitaxel (BCP) in
chemotherapy-naive patients with metastatic nonsquamous NSCLC (Figure 3)
• 1202 patients comprised the intention-to-treat (ITT) population
• Liver metastases at baseline, being a poor prognostic indicator, was included as a stratifica tion factor
Figure 3. IMpower150 Study Design
IHC, immunohistochemistry; IV, intravenous; PD, progressive disease; q3w, every 3 weeks; RECIST, Response Evaluation Criteria in Solid Tumors.
a Patients with a sensitizing EGFR mutation or ALK translocation must have PD or intolerance of treatment with ≥ 1 approved targeted therapies. b Atezolizumab 1200 mg IV q3w.
c Carboplatin area under the curve 6 IV q3w. d Paclitaxel 200 mg/m2 IV q3w. e Bevacizumab 15 mg/kg IV q3w.
• The co-primary endpoints, as previously reported, were PFS and OS in the ITT-wild-type population, which excluded patients with tumor EGFR or ALK genomic alterations17
• This presentation focuses on exploratory effic
a
cy and safety analyses of the ABCP regimen in patients
with liver metastases at baseline
- Presence of liver metastases was determined from baseline tumor assessment per investigator using
conventional imaging techniques (computed tomography [CT] scan with contrast imaging or magnetic
resonance imaging [non-contrast CT was permitted for patients with contraindications])
- For PFS and OS, Kaplan-Meier methodology was used to estimate the median and to construct survival curves for each treatment arm. The Brookmeyer-Crowley methodology and log-log transformation for
normal approximation was used to construct the 95% CI for the median for each treatment arm. The HR
was estimated with a Cox regression model, and the 95% CI was provided. Treatment comparisons
were based on the log-rank test
- The interaction between treatment and the status of liver metastases at baseline was examined using
a Cox regression model
- Objective response rate (ORR) and duration of response (DOR) were evaluated based on tumor assessments by investigators per RECIST 1.1
- Safety was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events
v4.0. Multiple occurrences of the same adverse event (AE) were counted once at the maximum grade
RESULTS• At the data cutoff date of January 22, 2018, the median follow-up was 19.6 months (range, 0.0-30.4) for ABCP, 19.6 months (range, 0.0-29.0) for ACP and 19.7 months (range, 0.0-32.6) for BCP
• Baseline demographics and characteristics of patients with liver metastases were generally balanced
between treatment arms (Table 1)
- Key baseline demographics and clinical characteristics shown include those with observed numerical differences between treatment arms in patients with and without liver metastases
Table 1. Key Baseline Demographics and Clinical Characteristics in Patients With and
Without Liver Metastases
With Liver Metastases Without Liver Metastases
ABCP(n = 52)
ACP(n = 53)
BCP(n = 57)
ABCP(n = 348)
ACP(n = 349)
BCP(n = 343)
Median age (range), years65
(39-79)59
(41-81)63
(48-83)63
(31-89)64
(32-85)
63(31-90)
Tobacco use, n (%)
Never 9 (17.3) 12 (22.6) 7 (12.3) 73 (21.0) 65 (18.6) 70 (20.4)
Current 11 (21.2) 14 (26.4) 16 (28.1) 79 (22.7) 84 (24.1) 76 (22.2)
Previous 32 (61.5) 27 (50.9) 34 (59.6) 196 (56.3) 200 (57.3) 197 (57.4)
ECOG PS, n (%)
0 16 (30.8) 23 (43.4) 22 (39.3)a 143 (41.4)b157 (45.0) 157 (46.0)
c
1 36 (69.2) 30 (56.6) 34 (60.7)a
202 (58.6)b
192 (55.0) 184 (54.0)c
ALK rearrangement status, n (%)
Positive 1 (1.9) 2 (3.8) 3 (5.3) 10 (2.9) 7 (2.0) 17 (5.0)
EGFR mutation status, n (%)
Positive 4 (7.7) 9 (17.0) 7 (12.3) 30 (8.6) 36 (10.3) 38 (11.1)
PD-L1 status, n (%)
TC3 or IC3d5 (9.6) 5 (9.4) 9 (15.8) 70 (20.1) 63 (18.1)e 64 (18.7)
TC1/2/3 or IC1/2/3f 22 (42.3) 25 (47.2) 26 (45.6) 187 (53.7) 188 (54.0)
e 169 (49.3)
TC0 and IC0g
30 (57.7) 28 (52.8) 31 (54.4) 161 (46.3) 160 (46.0)e
174 (50.7)
ECOG PS, Eastern Cooperative Oncology Group performance status; IC, tumor-infilt rating immune cell; TC, tumor cell.
a n = 56.
b n = 45.
c n = 341. d TC3 or IC3: PD-L1 on ≥ 50% of TC or ≥ 10% of IC. e n = 348. f TC1/2/3 or IC1/2/3: PD-L1 on ≥ 1% of TC or IC. g TC0 and IC0: PD-L1 on < 1% of TC and IC.
Atezolizumabb + Carboplatinc + Paclitaxeld
(ACP)
4 or 6 cycles
Atezolizumabb
Bevacizumabe + Carboplatinc + Paclitaxeld
(BCP)
4 or 6 cycles
Bevacizumabe
Su
rv
iv
al fo
llo
w-u
p
Stage IV or recurrent metastatic
nonsquamous NSCLC Chemotherapy naivea
Tumor tissue available for biomarker testing
Any PD-L1 IHC status
Stratification factors •Sex •PD-L1 IHC expression •Liver metastases
N = 1202
R 1:1:1
Atezolizumabb + Bevacizumabe
(ABCP)
4 or 6 cycles
Atezolizumabb +
Bevacizumabe
Maintenance therapy
(no crossover permitted)
Treated with atezolizumab until PD per RECIST 1.1 or loss of
clinical benefit
and/or
Treated with bevacizumab until PD per RECIST 1.1
+ Carboplatinc + Paclitaxeld
Effic
a
cy
• PFS benefit
was observed with ABCP vs BCP in patients with and without liver metastases (Figure 4)
Figure 4. PFS in Patients (A) With and (B) Without Liver Metastases
- An interaction test between treatment and liver metastases at baseline indicated that patients with liver metastases may have better treatment effect in PFS when treated with ABCP vs BCP (p = 0.07)
- The PFS HR for ABCP vs BCP in patients with liver metastases (HR, 0.41 [95% CI: 0.26, 0.62]) was similar after adjustment for tobacco use history (HR, 0.41 [95% CI: 0.26, 0.62]) and baseline ECOG PS (HR, 0.39 [95% CI: 0.26, 0.61])
• OS benefit
was seen with ABCP vs BCP in patients with liver metastases (Figure 5)
Figure 5. OS in Patients (A) With and (B) Without Liver Metastases
- An interaction test between treatment and liver metastases at baseline indicated that patients with liver metastases may have better treatment effect in OS when treated with ABCP vs BCP (p = 0.08)
- The OS HR for ABCP vs BCP in patients with liver metastases (HR, 0.52 [95% CI: 0.33, 0.82]) was similar after adjustment for tobacco use history (HR, 0.52 [95% CI: 0.33, 0.82]) and baseline ECOG PS (HR, 0.49 [95% CI: 0.31, 0.78])
2019 American Society of Clinical Oncology (ASCO) Annual Meeting – May 31-June 4, 2019, Chicago, IL, USA
Abstract #9012
Poster #335
HR, 0.41
(95% CI: 0.26, 0.62)
Median, 5.4 mo
(95% CI: 4.1, 6.0)
Median, 8.2 mo
(95% CI: 5.7, 10.3)
100
90
80
70
Pro
gres
sio
n-F
ree
S
urviva
l (%
)
60
50
40
30
20
10
0
0
ABCP
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
52 44 42 29 26 19 17 12 10 6 6 3 1 1
MonthsNo. at risk
BCP 57 45 35 21 11 3 1 1 1 1 1 1
HR, 0.52
(95% CI: 0.33, 0.82)
Median, 9.4 mo
(95% CI: 7.9, 11.7)
Median, 13.3 mo
(95% CI: 11.6, 26.1)
100
90
80
70
Ove
rall S
urv
iva
l (%
)
60
50
40
30
20
10
0
0
ABCP
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
52 46 44 41 37 36 30 22 19 13 10 5 3 1
Months
BCP 57 51 43 37 34 24 20 16 10 7 4 1 1 1
HR, 0.61
(95% CI: 0.52, 0.73)
Median, 7.0 mo
(95% CI: 6.4, 7.9)
Median, 8.4 mo
(95% CI: 8.0, 10.3)
100
90
80
70
Pro
gre
ss
io
n-F
re
e S
urv
iv
al (%
)
Months
60
50
40
30
20
10
0
0
ABCP
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
348 308 284 233 189 155 124 84 66 52 34 23 12 6 1 1BCP 343 308 262 192 143 101 73 42 25 15 7 6 2
HR, 0.82
(95% CI: 0.66, 1.02)
Median, 17.0 mo
(95% CI: 14.4, 19.2)
Median, 20.4 mo
(95% CI: 18.2, 25.2)
100
90
80
70O
ve
rall S
urviva
l (%
)
60
50
40
30
20
10
0
0
ABCP
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
348 321 307 292 271 252 235 186 143 117 83 57 35 17 2 2BCP 343 325 301 280 259 231 213 164 129 97 74 50 35 14 3 1 1
Months
HR, 0.82
(95% CI: 0.55, 1.21)
Median, 5.4 mo
(95% CI: 4.1, 6.0)
Median, 5.4 mo
(95% CI: 4.2, 5.7)
100
90
80
70
Pro
gre
ss
io
n-F
ree S
urv
iv
al (%
)
60
50
40
30
20
10
0
0
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Months
ACPBCP 57 45 35 21 11 3 1 1 1 1 1 1
53 43 35 18 11 8 8 7 5 3 3 1
HR, 0.87
(95% CI: 0.57, 1.32)
Median, 9.4 mo
(95% CI: 7.9, 11.7)
Median, 8.9 mo
(95% CI: 6.5, 12.6)
100
90
80
70
Ove
rall S
urv
iva
l (%
)
60
50
40
30
20
10
0
0
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Months
ACPBCP 57 51 43 37 34 24 20 16 10 7 4 1 1 1
53 48 44 36 27 24 20 14 11 9 7 5 2 1 1
HR, 0.90
(95% CI: 0.77, 1.06)
Median, 7.0 mo
(95% CI: 6.4, 7.9)
Median, 6.9 mo
(95% CI: 5.8, 7.1)
100
90
80
70
Pro
gre
ss
io
n-F
re
e S
urv
iv
al (%
)
60
50
40
30
20
10
0
0
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Months
ACP
BCP 343 308 262 192 143 101 73 42 25 15 7 6 2
349 300 267 186 143 97 79 59 43 28 22 13 6 3 1
HR, 0.84
(95% CI: 0.68, 1.04)
Median, 17.0 mo
(95% CI: 14.4, 19.2)
Median, 21.0 mo
(95% CI: 18.4, 24.0)
100
90
80
70
Ove
ra
ll S
urv
iv
al (%
)
60
50
40
30
20
10
0
0
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Months
ACPBCP 343 325 301 280 259 231 213 164 129 97 74 50 35 14 3 1 1
349 334 313 296 274 251 238 190 142 111 86 54 29 14 6
• The ABCP regimen showed higher ORR and durable DOR vs the BCP regimen in patients with and without liver metastases (Figure 6)
Figure 6. ORR and DOR in Patients With and Without Liver Metastasesa
a Patients with measurable disease at baseline.
Patterns of Progression
• The rate of progressive disease (PD) due to new lesions was comparable across treatment arms in
patients with or without liver metastases (Table 2)
- Higher rates of PD due to new lesions were observed in patients with vs without liver metastases
Table 2. PD Pattern in Patients With and Without Liver Metastases
PD per RECIST 1.1
With Liver Metastases Without Liver Metastases
ABCP
(n = 33)
ACP
(n = 39)
BCP
(n = 44)
ABCP
(n = 190)
ACP
(n = 251)
BCP
(n = 251)
PD at existing sites, n (%)a 22 (66.7) 26 (66.7) 29 (65.9) 128 (67.4) 163 (64.9) 172 (68.5)
In target lesion 18 (54.5) 21 (53.8) 22 (50.0) 104 (54.7) 133 (53.0) 136 (54.2)
In non-target lesion 8 (24.2) 12 (30.8) 12 (27.3) 45 (23.7) 50 (19.9) 62 (24.7)
PD at new sites, n (%)b 26 (78.8) 32 (82.1) 34 (77.3) 108 (56.8) 166 (66.1) 128 (51.0)
a First RECIST 1.1 PD at target or non-target lesions.
b First RECIST 1.1 PD due to new lesions.
• In patients with liver metastases, sites of new lesions included the liver, lungs, brain and bone (Table 3)
Table 3. Key Sites of New Lesions in Patients With and Without Liver Metastases
With Liver Metastases Without Liver Metastases
ABCP
(n = 33)
ACP
(n = 39)
BCP
(n = 44)
ABCP
(n = 190)
ACP
(n = 251)
BCP
(n = 251)
Sites of new lesions, n (%)
n 26 32 34 108 166 128
Liver 9 (27.3) 14 (35.9) 16 (36.4) 8 (4.2) 23 (9.2) 13 (5.2)
Lung 7 (21.2) 5 (12.8) 9 (20.5) 40 (21.1) 51 (20.3) 49 (19.5)
Brain 4 (12.1) 4 (10.3) 5 (11.4) 12 (6.3) 34 (13.5) 18 (7.2)
Bone 2 (6.1) 5 (12.8) 3 (6.8) 23 (12.1) 19 (7.6) 20 (8.0)
60.8
55.8
26.9
42.741.1 40.1
0
10
20
30
40
50
60
70
Ob
je
ctiv
e R
es
po
ns
e R
ate
(%
)
6.5
4.6
9.2
5.6
11.5
10.7
0n =
2 4 6 8 10 12 14
Months
With
ou
t
Liv
er M
eta
sta
ses
With
Liv
er M
eta
sta
se
s
ORR mDOR
ABCP ACP BCP
Difference, 19.7
(95% CI: –0.75, 40.18) Difference, 15.7
(95% CI: 8.03, 23.41)
Difference, 14.2
(95% CI: 33.65, 5.35)
Difference, 2.6
(95% CI: 5.03, 10.29)
With Liver Metastases Without Liver Metastases
n = 51 52 56
HR, 0.39
(95% CI:
0.21, 0.73)HR, 0.68
(95% CI:
0.33, 1.40)
HR, 0.43
(95% CI:
0.33, 0.56)HR, 0.53
(95% CI: 0.40, 0.69)
346 349 337
13
514
919
323
14
31
Safety
• ABCP was tolerable in patients with and without liver metastases (Table 4)
- G rade 3/4 treatment-related AEs (TRAEs) were reported in 52.1%, 36.5% and 54.5% of patients with liver metastases and 57.4%, 44.0% and 47.5% of patients without liver metastases in the ABCP, ACP
and BCP arms, respectively
Table 4. Safety Summary
With Liver Metastases Without Liver Metastases
ABCP
(n = 48)
ACP
(n = 52)
BCP
(n = 55)
ABCP
(n = 345)
ACP
(n = 348)
BCP
(n = 339)
Patients with ≥ 1, n (%)
AE 48 (100) 49 (94.2) 55 (100) 338 (98.0) 342 (98.3) 335 (98.8)
Grade 3/4 28 (58.3) 29 (55.8) 35 (63.6) 222 (64.3) 201 (57.8) 195 (57.5)
Grade 5 6 (12.5) 1 (1.9) 4 (7.3) 18 (5.2) 9 (2.6) 17 (5.0)
TRAE 43 (89.6) 45 (86.5) 51 (92.7) 327 (94.8) 332 (95.4) 326 (96.2)
G rade 3/4 25 (52.1) 19 (36.5) 30 (54.5) 198 (57.4) 153 (44.0) 161 (47.5)
Grade 5a 3 (6.3) 1 (1.9) 2 (3.6) 8 (2.3) 3 (0.9) 7 (2.1)
Serious AE 20 (41.7) 26 (50.0) 27 (49.1) 154 (44.6) 131 (37.6) 108 (31.9)
Serious TRAE 7 (14.6) 13 (25.0) 18 (32.7) 96 (27.8) 65 (18.7) 60 (17.7)
AE leading to any treatment discontinuation
13 (27.1) 6 (11.5) 20 (36.4) 120 (34.8) 47 (13.5) 78 (23.0)
AE leading to any dose modific
a
tion/interruption26 (54.2) 23 (44.2) 26 (47.3) 220 (63.8) 184 (52.9) 162 (47.8)
a In patients with liver metastases: hemoptysis (n = 2) and febrile neutropenia (n = 1) with ABCP; acute respiratory failure (n = 1) with ACP; pulmonary
embolism and pulmonary hemorrhage (n = 1 each) with BCP. In patients without liver metastases, febrile neutropenia (n = 2), pulmonary hemorrhage (n = 2), intestinal obstruction, cerebrovascular accident, hemoptysis and aortic dissection (n = 1 each) with ABCP; acute hepatitis, interstitial lung disease and cardiac arrest (n = 1 each) with ACP; intestinal perforation (n = 2), sepsis, posterior reversible encephalopathy syndrome, pulmonary embolism, pulmonary hemorrhage and pneumonia (n = 1 each) with BCP.
CONCLUSIONS• In patients with NSCLC, presence of liver metastases represents a poor prognostic factor, with higher
rates of PD due to new lesions vs those without liver metastases, which might be suggestive of more
aggressive or dispersed disease in these patients
• Improved clinical outcomes with ABCP vs BCP were observed in patients with and without liver metastases
- Higher ORR and durable DOR were also seen with ABCP vs BCP in patients with liver metastases
• Interaction tests suggested a trend towards improved PFS and OS favoring ABCP in patients with liver metastases; lack of statistical signific
a
nce is likely due to small sample size
• Patients with liver metastases showed a greater survival benefit
with ABCP vs BCP than patients without
baseline liver metastases (OS HR, 0.52 vs 0.82)
• ABCP was well tolerated regardless of baseline liver metastases status
- The safety profil
e
of ABCP in patients with liver metastases remained consistent with that observed in
the ITT population;18 there were no new safety signals in this patient subgroup
• ABCP is an important new treatment option for patients with advanced nonsquamous NSCLC, particularly
those with liver metastases
REFERENCES
ACKNOWLEDGMENTS• The patients and their families
• The investigators and clinical study sites
• This study is sponsored by F. Hoffmann-La Roche, Ltd
• Medical writing assistance for this poster was provided by Preshita Gadkari, PhD,
of Health Interactions and funded by F. Hoffmann-La Roche, Ltd
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16. Zitvogel L, et al. Immunity. 2013;39(1):74-88.
17. Socinski MA, et al. N Engl J Med. 2018;378(24):2288-2301.
18. Reck M, et al. Lancet Respir Med. 2019;7(5):387-401.
A. With Liver Metastases
ABCP vs BCP
Without Liver Metastases
ABCP vs BCP
With Liver Metastases
ABCP vs BCP
Without Liver Metastases
ABCP vs BCP
With Liver Metastases
ACP vs BCP
Without Liver Metastases
ACP vs BCP
With Liver Metastases
ACP vs BCP
Without Liver Metastases
ACP vs BCP
A.
B.
B.
ABCP
BCPACP
For questions or comments on this poster, please contact Dr Mark A. Socinski at [email protected]
Copies of this poster obtained through Quick Response (QR) Code are for personal use only
and may not be reproduced without permission from ASCO® and the author of this poster
ABCP
BCPACP
IMpower150: Analysis of Effica c y in Patients With Liver MetastasesMark A. Socinski,1 Robert Jotte,2 Federico Cappuzzo,3 Tony Mok,4 Howard West,5 Makota Nishio,6 Vassiliki A. Papadimitrakopoulou,7 Francisco Orlandi,8 Daniil Stroyakovskiy,9 Christian A. Thomas,10 Naoyuki Nogami,11 Fabrice Barlesi,12 Anthony Lee,13 Geetha Shankar,13 Wei Yu,13 Marcus Ballinger,13 Ilze Bara,13 Alan Sandler,13 Martin Reck14
1AdventHealth Cancer Institute, Orlando, FL; 2Rocky Mountain Cancer Centers, Denver, CO; 3Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy; 4Chinese University of Hong Kong, Hong Kong, China; 5Swedish Cancer Institute, Seattle, WA; 6The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; 7The University of Texas MD Anderson Cancer Center, Houston, TX; 8Instituto Nacional del Torax, Santiago, Chile; 9Moscow City Oncology Hospital, Moscow, Russia; 10New England Cancer Specialists, Scarborough, ME; 11National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan; 12Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille, France;
13Genentech, Inc., South San Francisco, CA; 14Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany
BACKGROUNDNSCLC and Liver Metastases
• For patients with advanced non-small cell lung cancer (NSCLC), recommended firs t-line treatments include:1,2
- Tyrosine kinase inhibitors for patients with oncogenic alterations (e.g., EGFR mutations or ALK translocations)
- Pembrolizumab (anti–programmed death-1 [PD-1]) monotherapy for patients with high programmed
death-ligand 1 (PD-L1)–expressing tumors (tumor proportion score ≥ 50%)
- Platinum-based chemotherapy alone or with bevacizumab,3 pembrolizumab4 or atezolizumab + bevacizumab
• Tumor metastases to the liver are common in patients with lung cancer and are associated with a poorer
prognosis compared with metastases to other sites.5 Additionally, the presence of liver metastases may
signal a high tumor burden, and VEGF activation may play a role at specific
organs/sites6,7
• Patients with liver metastases experience limited benefit
with anti–PD-L1 or anti–PD-1 monotherapies6,8,9
• Combination regimens of checkpoint inhibitors with nab-paclitaxel have also shown limited effic
a
cy in
this population10
• Thus, additional treatment options are needed for these patients
Combining Atezolizumab + Bevacizumab + Chemotherapy
• Atezolizumab is a monoclonal anti≥PD-L1 antibody that inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, thus restoring tumor-specific
immunity11,12
• Atezolizumab, as monotherapy and in combination with chemotherapy, has shown effica cy in patients
with NSCLC13,14
• Bevacizumab, a recombinant humanized VEGF monoclonal antibody, combined with chemotherapy
had a signific
a
ntly better outcome for overall survival (OS) than chemotherapy alone in patients with
advanced NSCLC in a Phase II/III study (E4599; NCT00021060)3
• In a subpopulation of patients with baseline liver metastases in E4599, the combination of bevacizumab plus chemotherapy demonstrated improved OS vs chemotherapy alone (Figure 1)
Figure 1. Bevacizumab With Chemotherapy Demonstrated OS Benefit
vs Chemotherapy
Alone in Patients With Baseline Liver Metastases (historical data from E4599)
BCP, bevacizumab + carboplatin + paclitaxel; CP, carboplatin + paclitaxel; HR, hazard ratio.
• In combination with bevacizumab and chemotherapy, atezolizumab’s T-cell–mediated cancer cell killing
may be further enhanced through both reversal of VEGF-mediated immunosuppression15 and
chemotherapy-induced cell death16 (Figure 2)
Figure 2. Rationale for the Combination of Atezolizumab With Bevacizumab and Chemotherapy
DC, dendritic cell; MDSC, myeloid-derived suppressor cell; Treg, regulatory T cell.
• The randomized Phase III IMpower150 study demonstrated statistically significant and clinically meaningful improvements with atezolizumab + bevacizumab + chemotherapy vs bevacizumab +
chemotherapy in progression-free survival (PFS; HR, 0.62 [95% CI: 0.52, 0.74]; p < 0.001) and
OS (HR, 0.78 [95% CI: 0.64, 0.96]; p = 0.02)17
• Notably, the combination of atezolizumab + bevacizumab + chemotherapy showed clinical benefit in the subgroup of patients with baseline liver metastases compared with the combination of
bevacizumab + chemotherapy18
• The objective of this exploratory analysis was to further evaluate the subgroup of patients with baseline
liver metastases treated with atezolizumab + bevacizumab + chemotherapy in the IMpower150 study,
including baseline characteristics, effic
a
cy and safety
100
90
80
70
Ov
era
ll S
urv
iva
l (%
)
Months
60
50
40
30
20
10
0
0
93
CP
BCP 71 49 31 15 6 5 1 1
74 49 21 13 7 3 2 1 0
5 10 15 20 25 30 35 40
HR, 0.68
(95% CI: 0.49, 0.96)
No. at risk
Tumor cells
Dendritic cell
Activated T cells
Tumor antigens
ChemotherapyPromotes recruitment of DCs to the
site of cell death16
Atezolizumab Restores anti-cancer immunity,11,12
with activity further enhanced through
VEGF-mediated immunomodulatory
effects and chemotherapy-induced
tumor antigen exposure
Bevacizumab Normalizes the tumor vasculature, increasing T-cell infiltration12
Bevacizumab Decreases the activity of
immunosuppressive cells
(MDSCs and Tregs)12
Bevacizumab Promotes DC maturation12
AtezolizumabPromotes T-cell activation by allowing
B7.1 co-stimulation11,12
METHODSStudy Design and Patient Population
• IMpower150 (NCT02366143) is a randomized, open-label, international, Phase III study designed to evaluate the effic
a
cy and safety of atezolizumab + carboplatin + paclitaxel (ACP) or atezolizumab +
bevacizumab + carboplatin + paclitaxel (ABCP) vs bevacizumab + carboplatin + paclitaxel (BCP) in
chemotherapy-naive patients with metastatic nonsquamous NSCLC (Figure 3)
• 1202 patients comprised the intention-to-treat (ITT) population
• Liver metastases at baseline, being a poor prognostic indicator, was included as a stratifica tion factor
Figure 3. IMpower150 Study Design
IHC, immunohistochemistry; IV, intravenous; PD, progressive disease; q3w, every 3 weeks; RECIST, Response Evaluation Criteria in Solid Tumors.
a Patients with a sensitizing EGFR mutation or ALK translocation must have PD or intolerance of treatment with ≥ 1 approved targeted therapies. b Atezolizumab 1200 mg IV q3w.
c Carboplatin area under the curve 6 IV q3w. d Paclitaxel 200 mg/m2 IV q3w. e Bevacizumab 15 mg/kg IV q3w.
• The co-primary endpoints, as previously reported, were PFS and OS in the ITT-wild-type population, which excluded patients with tumor EGFR or ALK genomic alterations17
• This presentation focuses on exploratory effic
a
cy and safety analyses of the ABCP regimen in patients
with liver metastases at baseline
- Presence of liver metastases was determined from baseline tumor assessment per investigator using
conventional imaging techniques (computed tomography [CT] scan with contrast imaging or magnetic
resonance imaging [non-contrast CT was permitted for patients with contraindications])
- For PFS and OS, Kaplan-Meier methodology was used to estimate the median and to construct survival curves for each treatment arm. The Brookmeyer-Crowley methodology and log-log transformation for
normal approximation was used to construct the 95% CI for the median for each treatment arm. The HR
was estimated with a Cox regression model, and the 95% CI was provided. Treatment comparisons
were based on the log-rank test
- The interaction between treatment and the status of liver metastases at baseline was examined using
a Cox regression model
- Objective response rate (ORR) and duration of response (DOR) were evaluated based on tumor assessments by investigators per RECIST 1.1
- Safety was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events
v4.0. Multiple occurrences of the same adverse event (AE) were counted once at the maximum grade
RESULTS• At the data cutoff date of January 22, 2018, the median follow-up was 19.6 months (range, 0.0-30.4) for ABCP, 19.6 months (range, 0.0-29.0) for ACP and 19.7 months (range, 0.0-32.6) for BCP
• Baseline demographics and characteristics of patients with liver metastases were generally balanced
between treatment arms (Table 1)
- Key baseline demographics and clinical characteristics shown include those with observed numerical differences between treatment arms in patients with and without liver metastases
Table 1. Key Baseline Demographics and Clinical Characteristics in Patients With and
Without Liver Metastases
With Liver Metastases Without Liver Metastases
ABCP(n = 52)
ACP(n = 53)
BCP(n = 57)
ABCP(n = 348)
ACP(n = 349)
BCP(n = 343)
Median age (range), years65
(39-79)59
(41-81)63
(48-83)63
(31-89)64
(32-85)
63(31-90)
Tobacco use, n (%)
Never 9 (17.3) 12 (22.6) 7 (12.3) 73 (21.0) 65 (18.6) 70 (20.4)
Current 11 (21.2) 14 (26.4) 16 (28.1) 79 (22.7) 84 (24.1) 76 (22.2)
Previous 32 (61.5) 27 (50.9) 34 (59.6) 196 (56.3) 200 (57.3) 197 (57.4)
ECOG PS, n (%)
0 16 (30.8) 23 (43.4) 22 (39.3)a 143 (41.4)b157 (45.0) 157 (46.0)
c
1 36 (69.2) 30 (56.6) 34 (60.7)a
202 (58.6)b
192 (55.0) 184 (54.0)c
ALK rearrangement status, n (%)
Positive 1 (1.9) 2 (3.8) 3 (5.3) 10 (2.9) 7 (2.0) 17 (5.0)
EGFR mutation status, n (%)
Positive 4 (7.7) 9 (17.0) 7 (12.3) 30 (8.6) 36 (10.3) 38 (11.1)
PD-L1 status, n (%)
TC3 or IC3d5 (9.6) 5 (9.4) 9 (15.8) 70 (20.1) 63 (18.1)e 64 (18.7)
TC1/2/3 or IC1/2/3f 22 (42.3) 25 (47.2) 26 (45.6) 187 (53.7) 188 (54.0)
e 169 (49.3)
TC0 and IC0g
30 (57.7) 28 (52.8) 31 (54.4) 161 (46.3) 160 (46.0)e
174 (50.7)
ECOG PS, Eastern Cooperative Oncology Group performance status; IC, tumor-infilt rating immune cell; TC, tumor cell.
a n = 56.
b n = 45.
c n = 341. d TC3 or IC3: PD-L1 on ≥ 50% of TC or ≥ 10% of IC. e n = 348. f TC1/2/3 or IC1/2/3: PD-L1 on ≥ 1% of TC or IC. g TC0 and IC0: PD-L1 on < 1% of TC and IC.
Atezolizumabb + Carboplatinc + Paclitaxeld
(ACP)
4 or 6 cycles
Atezolizumabb
Bevacizumabe + Carboplatinc + Paclitaxeld
(BCP)
4 or 6 cycles
Bevacizumabe
Su
rviv
al
follo
w-u
p
Stage IV or recurrent metastatic
nonsquamous NSCLC Chemotherapy naivea
Tumor tissue available for biomarker testing
Any PD-L1 IHC status
Stratification factors •Sex •PD-L1 IHC expression •Liver metastases
N = 1202
R 1:1:1
Atezolizumabb + Bevacizumabe
(ABCP)
4 or 6 cycles
Atezolizumabb +
Bevacizumabe
Maintenance therapy
(no crossover permitted)
Treated with atezolizumab until PD per RECIST 1.1 or loss of
clinical benefit
and/or
Treated with bevacizumab until PD per RECIST 1.1
+ Carboplatinc + Paclitaxeld
Effic
a
cy
• PFS benefit
was observed with ABCP vs BCP in patients with and without liver metastases (Figure 4)
Figure 4. PFS in Patients (A) With and (B) Without Liver Metastases
- An interaction test between treatment and liver metastases at baseline indicated that patients with liver metastases may have better treatment effect in PFS when treated with ABCP vs BCP (p = 0.07)
- The PFS HR for ABCP vs BCP in patients with liver metastases (HR, 0.41 [95% CI: 0.26, 0.62]) was similar after adjustment for tobacco use history (HR, 0.41 [95% CI: 0.26, 0.62]) and baseline ECOG PS (HR, 0.39 [95% CI: 0.26, 0.61])
• OS benefit
was seen with ABCP vs BCP in patients with liver metastases (Figure 5)
Figure 5. OS in Patients (A) With and (B) Without Liver Metastases
- An interaction test between treatment and liver metastases at baseline indicated that patients with liver metastases may have better treatment effect in OS when treated with ABCP vs BCP (p = 0.08)
- The OS HR for ABCP vs BCP in patients with liver metastases (HR, 0.52 [95% CI: 0.33, 0.82]) was similar after adjustment for tobacco use history (HR, 0.52 [95% CI: 0.33, 0.82]) and baseline ECOG PS (HR, 0.49 [95% CI: 0.31, 0.78])
2019 American Society of Clinical Oncology (ASCO) Annual Meeting – May 31-June 4, 2019, Chicago, IL, USA
Abstract #9012
Poster #335
HR, 0.41
(95% CI: 0.26, 0.62)
Median, 5.4 mo
(95% CI: 4.1, 6.0)
Median, 8.2 mo
(95% CI: 5.7, 10.3)
100
90
80
70
Pro
gre
ss
ion
-Fre
e S
urv
ival
(%)
60
50
40
30
20
10
0
0
ABCP
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
52 44 42 29 26 19 17 12 10 6 6 3 1 1
MonthsNo. at risk
BCP 57 45 35 21 11 3 1 1 1 1 1 1
HR, 0.52
(95% CI: 0.33, 0.82)
Median, 9.4 mo
(95% CI: 7.9, 11.7)
Median, 13.3 mo
(95% CI: 11.6, 26.1)
100
90
80
70
Overa
ll S
urv
ival
(%)
60
50
40
30
20
10
0
0
ABCP
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
52 46 44 41 37 36 30 22 19 13 10 5 3 1
Months
BCP 57 51 43 37 34 24 20 16 10 7 4 1 1 1
HR, 0.61
(95% CI: 0.52, 0.73)
Median, 7.0 mo
(95% CI: 6.4, 7.9)
Median, 8.4 mo
(95% CI: 8.0, 10.3)
100
90
80
70
Pro
gre
ssio
n-F
ree S
urv
iva
l (%
)
Months
60
50
40
30
20
10
0
0
ABCP
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
348 308 284 233 189 155 124 84 66 52 34 23 12 6 1 1BCP 343 308 262 192 143 101 73 42 25 15 7 6 2
HR, 0.82
(95% CI: 0.66, 1.02)
Median, 17.0 mo
(95% CI: 14.4, 19.2)
Median, 20.4 mo
(95% CI: 18.2, 25.2)
100
90
80
70
Ove
rall S
urv
iva
l (%
)
60
50
40
30
20
10
0
0
ABCP
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
348 321 307 292 271 252 235 186 143 117 83 57 35 17 2 2BCP 343 325 301 280 259 231 213 164 129 97 74 50 35 14 3 1 1
Months
HR, 0.82
(95% CI: 0.55, 1.21)
Median, 5.4 mo
(95% CI: 4.1, 6.0)
Median, 5.4 mo
(95% CI: 4.2, 5.7)
100
90
80
70
Pro
gre
ssio
n-F
ree S
urv
ival
(%)
60
50
40
30
20
10
0
0
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Months
ACPBCP 57 45 35 21 11 3 1 1 1 1 1 1
53 43 35 18 11 8 8 7 5 3 3 1
HR, 0.87
(95% CI: 0.57, 1.32)
Median, 9.4 mo
(95% CI: 7.9, 11.7)
Median, 8.9 mo
(95% CI: 6.5, 12.6)
100
90
80
70
Overa
ll S
urv
ival
(%)
60
50
40
30
20
10
0
0
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Months
ACPBCP 57 51 43 37 34 24 20 16 10 7 4 1 1 1
53 48 44 36 27 24 20 14 11 9 7 5 2 1 1
HR, 0.90
(95% CI: 0.77, 1.06)
Median, 7.0 mo
(95% CI: 6.4, 7.9)
Median, 6.9 mo
(95% CI: 5.8, 7.1)
100
90
80
70
Pro
gre
ssio
n-F
ree S
urv
iva
l (%
)
60
50
40
30
20
10
0
0
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Months
ACP
BCP 343 308 262 192 143 101 73 42 25 15 7 6 2
349 300 267 186 143 97 79 59 43 28 22 13 6 3 1
HR, 0.84
(95% CI: 0.68, 1.04)
Median, 17.0 mo
(95% CI: 14.4, 19.2)
Median, 21.0 mo
(95% CI: 18.4, 24.0)
100
90
80
70
Ov
era
ll S
urv
iva
l (%
)
60
50
40
30
20
10
0
0
No. at risk
2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34
Months
ACPBCP 343 325 301 280 259 231 213 164 129 97 74 50 35 14 3 1 1
349 334 313 296 274 251 238 190 142 111 86 54 29 14 6
• The ABCP regimen showed higher ORR and durable DOR vs the BCP regimen in patients with and without liver metastases (Figure 6)
Figure 6. ORR and DOR in Patients With and Without Liver Metastasesa
a Patients with measurable disease at baseline.
Patterns of Progression
• The rate of progressive disease (PD) due to new lesions was comparable across treatment arms in
patients with or without liver metastases (Table 2)
- Higher rates of PD due to new lesions were observed in patients with vs without liver metastases
Table 2. PD Pattern in Patients With and Without Liver Metastases
PD per RECIST 1.1
With Liver Metastases Without Liver Metastases
ABCP
(n = 33)
ACP
(n = 39)
BCP
(n = 44)
ABCP
(n = 190)
ACP
(n = 251)
BCP
(n = 251)
PD at existing sites, n (%)a 22 (66.7) 26 (66.7) 29 (65.9) 128 (67.4) 163 (64.9) 172 (68.5)
In target lesion 18 (54.5) 21 (53.8) 22 (50.0) 104 (54.7) 133 (53.0) 136 (54.2)
In non-target lesion 8 (24.2) 12 (30.8) 12 (27.3) 45 (23.7) 50 (19.9) 62 (24.7)
PD at new sites, n (%)b 26 (78.8) 32 (82.1) 34 (77.3) 108 (56.8) 166 (66.1) 128 (51.0)
a First RECIST 1.1 PD at target or non-target lesions.
b First RECIST 1.1 PD due to new lesions.
• In patients with liver metastases, sites of new lesions included the liver, lungs, brain and bone (Table 3)
Table 3. Key Sites of New Lesions in Patients With and Without Liver Metastases
With Liver Metastases Without Liver Metastases
ABCP
(n = 33)
ACP
(n = 39)
BCP
(n = 44)
ABCP
(n = 190)
ACP
(n = 251)
BCP
(n = 251)
Sites of new lesions, n (%)
n 26 32 34 108 166 128
Liver 9 (27.3) 14 (35.9) 16 (36.4) 8 (4.2) 23 (9.2) 13 (5.2)
Lung 7 (21.2) 5 (12.8) 9 (20.5) 40 (21.1) 51 (20.3) 49 (19.5)
Brain 4 (12.1) 4 (10.3) 5 (11.4) 12 (6.3) 34 (13.5) 18 (7.2)
Bone 2 (6.1) 5 (12.8) 3 (6.8) 23 (12.1) 19 (7.6) 20 (8.0)
60.8
55.8
26.9
42.741.1 40.1
0
10
20
30
40
50
60
70
Ob
jec
tiv
e R
es
po
ns
e R
ate
(%
)
6.5
4.6
9.2
5.6
11.5
10.7
0n =
2 4 6 8 10 12 14
Months
Wit
ho
ut
Liv
er
Me
tas
tas
es
Wit
h
Liv
er
Me
tas
tas
es
ORR mDOR
ABCP ACP BCP
Difference, 19.7
(95% CI: –0.75, 40.18) Difference, 15.7
(95% CI: 8.03, 23.41)
Difference, 14.2
(95% CI: 33.65, 5.35)
Difference, 2.6
(95% CI: 5.03, 10.29)
With Liver Metastases Without Liver Metastases
n = 51 52 56
HR, 0.39
(95% CI:
0.21, 0.73)HR, 0.68
(95% CI:
0.33, 1.40)
HR, 0.43
(95% CI:
0.33, 0.56)HR, 0.53
(95% CI: 0.40, 0.69)
346 349 337
135
14
91
93
23
14
31
Safety
• ABCP was tolerable in patients with and without liver metastases (Table 4)
- G rade 3/4 treatment-related AEs (TRAEs) were reported in 52.1%, 36.5% and 54.5% of patients with liver metastases and 57.4%, 44.0% and 47.5% of patients without liver metastases in the ABCP, ACP
and BCP arms, respectively
Table 4. Safety Summary
With Liver Metastases Without Liver Metastases
ABCP
(n = 48)
ACP
(n = 52)
BCP
(n = 55)
ABCP
(n = 345)
ACP
(n = 348)
BCP
(n = 339)
Patients with ≥ 1, n (%)
AE 48 (100) 49 (94.2) 55 (100) 338 (98.0) 342 (98.3) 335 (98.8)
Grade 3/4 28 (58.3) 29 (55.8) 35 (63.6) 222 (64.3) 201 (57.8) 195 (57.5)
Grade 5 6 (12.5) 1 (1.9) 4 (7.3) 18 (5.2) 9 (2.6) 17 (5.0)
TRAE 43 (89.6) 45 (86.5) 51 (92.7) 327 (94.8) 332 (95.4) 326 (96.2)
G rade 3/4 25 (52.1) 19 (36.5) 30 (54.5) 198 (57.4) 153 (44.0) 161 (47.5)
Grade 5a 3 (6.3) 1 (1.9) 2 (3.6) 8 (2.3) 3 (0.9) 7 (2.1)
Serious AE 20 (41.7) 26 (50.0) 27 (49.1) 154 (44.6) 131 (37.6) 108 (31.9)
Serious TRAE 7 (14.6) 13 (25.0) 18 (32.7) 96 (27.8) 65 (18.7) 60 (17.7)
AE leading to any treatment discontinuation
13 (27.1) 6 (11.5) 20 (36.4) 120 (34.8) 47 (13.5) 78 (23.0)
AE leading to any dose modific
a
tion/interruption26 (54.2) 23 (44.2) 26 (47.3) 220 (63.8) 184 (52.9) 162 (47.8)
a In patients with liver metastases: hemoptysis (n = 2) and febrile neutropenia (n = 1) with ABCP; acute respiratory failure (n = 1) with ACP; pulmonary
embolism and pulmonary hemorrhage (n = 1 each) with BCP. In patients without liver metastases, febrile neutropenia (n = 2), pulmonary hemorrhage (n = 2), intestinal obstruction, cerebrovascular accident, hemoptysis and aortic dissection (n = 1 each) with ABCP; acute hepatitis, interstitial lung disease and cardiac arrest (n = 1 each) with ACP; intestinal perforation (n = 2), sepsis, posterior reversible encephalopathy syndrome, pulmonary embolism, pulmonary hemorrhage and pneumonia (n = 1 each) with BCP.
CONCLUSIONS• In patients with NSCLC, presence of liver metastases represents a poor prognostic factor, with higher
rates of PD due to new lesions vs those without liver metastases, which might be suggestive of more
aggressive or dispersed disease in these patients
• Improved clinical outcomes with ABCP vs BCP were observed in patients with and without liver metastases
- Higher ORR and durable DOR were also seen with ABCP vs BCP in patients with liver metastases
• Interaction tests suggested a trend towards improved PFS and OS favoring ABCP in patients with liver metastases; lack of statistical signific
a
nce is likely due to small sample size
• Patients with liver metastases showed a greater survival benefit
with ABCP vs BCP than patients without
baseline liver metastases (OS HR, 0.52 vs 0.82)
• ABCP was well tolerated regardless of baseline liver metastases status
- The safety profil
e
of ABCP in patients with liver metastases remained consistent with that observed in
the ITT population;18 there were no new safety signals in this patient subgroup
• ABCP is an important new treatment option for patients with advanced nonsquamous NSCLC, particularly
those with liver metastases
REFERENCES
ACKNOWLEDGMENTS• The patients and their families
• The investigators and clinical study sites
• This study is sponsored by F. Hoffmann-La Roche, Ltd
• Medical writing assistance for this poster was provided by Preshita Gadkari, PhD,
of Health Interactions and funded by F. Hoffmann-La Roche, Ltd
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A. With Liver Metastases
ABCP vs BCP
Without Liver Metastases
ABCP vs BCP
With Liver Metastases
ABCP vs BCP
Without Liver Metastases
ABCP vs BCP
With Liver Metastases
ACP vs BCP
Without Liver Metastases
ACP vs BCP
With Liver Metastases
ACP vs BCP
Without Liver Metastases
ACP vs BCP
A.
B.
B.
ABCP
BCPACP
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ABCP
BCPACP
1L NSCLC: IMpower150
• Liver Metastases
Socinski M, et al. ASCO 2019
1L NSCLC: KEYNOTE-189