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 Mark.Socinski.MD@AdventHealth.com

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

For questions or comments on this poster, please contact Dr Mark A. Socinski at Mark.Socinski.MD@AdventHealth.com

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ABCP

BCPACP

1L NSCLC: IMpower150

• Liver Metastases

Socinski M, et al. ASCO 2019

1L NSCLC: KEYNOTE-189