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1. New Thinking, New Strategies in the Treatment of
Advanced NSCLC Without Driver Mutations
Jamie E. Chaft, MD
Associate Attending Physician
Memorial Sloan Kettering Cancer Center

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COMMERCIAL SUPPORT
This activity is supported by an independent educational grant from Lilly.

3. Disclosures
Dr. Chaft discloses the following commercial relationships:
Research support: AstraZeneca, Bristol-Myers Squibb, Genentech, and Merck

4. Learning Objectives
NSCLC = non-small cell lung cancer.
Assess molecular and clinical factors that can refine personalized care
plans for patients with advanced NSCLC without driver mutations
Evaluate efficacy and safety data on first- and second-line treatment
strategies for patients with advanced NSCLC without driver mutations
Discuss the rationale supporting angiogenesis as a therapeutic target
in advanced NSCLC

5. Lung Cancer Treatment Over Two Years Ago
EGFR = epidermal growth factor receptor; ALK = anaplastic lymphoma kinase; PD-L1 = programmed death-ligand 1; IO = immuno-oncology.
Image courtesy of Jamie Chaft, MD.
Test for EGFR, ALK, ROS1
Targeted
therapy
Platinum-based chemotherapy
Docetaxel
or targeted
therapy
Newly
diagnosed
Supportive care
Pembrolizumab
Nivolumab
atezolizumab

6. Case Study 1
CT = computed tomography; TTF1+ = thyroid transcription factor 1-positive.
68-year-old man, former smoker, was found to have a right apical
mass and bilateral pulmonary metastases on a screening chest
CT
CT-guided core needle biopsy of the lung demonstrates a TTF1+
adenocarcinoma

7. Case Study 1 (cont.)
He feels well and relays that he wants the best therapy with the least
toxicity. You advise which of the following:
a. Start cisplatin + pemetrexed
b. Await results of testing for PD-L1
c. Await results of PD-L1, EGFR, ALK, ROS1, and BRAF testing
d. Start pembrolizumab + carboplatin + pemetrexed
e. Start pembrolizumab

8. Guidelines Recommend Upfront Biomarker Testing
NCCN = National Comprehensive Cancer Network.
NCCN, 2019.

9. Genomic Landscape of Lung Adenocarcinoma
MSK-IMPACT™ = Memorial Sloan Kettering—Integrated Mutation Profiling of Actionable Cancer Targets.
Jordan et al, 2016.
915 tumor samples from
patients with lung
adenocarcinoma
sequenced on MSK-
IMPACT™

10. Case Study 1 (cont.)
Genomics testing revealed a KRAS G12C, but PD-L1 wasn’t ordered
properly. He still feels well. You recommend:
a. Start cisplatin and pemetrexed
b. Await results of testing for PD-L1
c. Start carboplatin + paclitaxel + bevacizumab
d. Start pembrolizumab + carboplatin + pemetrexed
e. Start pembrolizumab

11. Pembrolizumaba
(Anti PD-1)
Nivolumaba
(Anti PD-1)
Durvalumab
(Anti PD-L1)
Atezolizumab
(Anti PD-L1)
Diagnostic partner Dako Dako Ventana Ventana
Clones 22C3 28-8 SP263 SP142
Machines utilized Link 48 Link 48 BenchMark ULTRA BenchMark ULTRA
Compartment TM TM TM TC/IC
Variables % of cells % of cells % of cells % of cells
Definition of positive
PD-L1(+): >1%
Strong(+): >50%
PD-L1(+): >1%
Strong(+): >5%
PD-L1(+): ≥25%
TC / IC 3(+)
TC / IC 2(+)
TC / IC 1(+)
TC / IC 0(−)
PD-L1 IHC Assays
aFDA-approved assays.
IHC = immunohistochemistry; TM = tumor cell membrane; TC = tumor cell; IC = immune cell.
Roach et al, 2016; Phillips et al, 2015; Diggs & Hsueh, 2017; Vennapusa et al, 2019.

12. Blueprint PD-L1 IHC Assay Comparison Project
Tumor proportion score by case (n=39)
for each assay
Data points represent the mean score
from three pathologists for each assay
on each case
Superimposed lines/points indicate
identical TPS values
TPS = tumor proportion score; pembro = pembrolizumab; nivo = nivolumab; atezo = atezolizumab; durva = durvalumab.
Hirsch et al, 2017.
Phase 1
100
80
60
40
20
0
1 3 5 7 9 1113151719
%TumorCellStaining
232527293133353721 39
Cases
22C3 (pembro)
28-8 (nivo)
SP142 (atezo)
SP263 (durva)

13. Case Study 1 (cont.)
bx = biopsy; TMB = tumor mutational burden; mut/Mb = mutations per megabase; AE = adverse event.
You start folic acid, order carboplatin + pemetrexed + pembrolizumab to
begin next week while awaiting PD-L1
His tumor bx returns: PD-L1 90%, TMB 8 mut/Mb. What do you do?
a. Switch the treatment plan to pembrolizumab alone
b. Proceed with carboplatin + pemetrexed + pembrolizumab
c. Suggest carboplatin + pemetrexed without pembrolizumab due to increased AE of
combination
d. Suggest nivolumab monotherapy
e. Discuss ipilimumab + nivolumab

14. First-Line Pembro Versus Chemotherapy in PD-L1 High
ECOG = Eastern Cooperative Oncology Group; PS = performance status; pts = patients; IV = intravenous; q3w = every three weeks; PD = progressive disease;
PFS = progression-free survival; ORR = overall response rate; OS = overall survival.
Reck et al, 2016.
Primary end point: PFS
Secondary end points: ORR, OS, and safety
KEYNOTE-024
Pts with stage IV NSCLC
and ECOG PS 0/1, no
previous systemic therapy,
no actionable EGFR/ALK
mutations, and
PD-L1 TPS ≥50%
(N=305)
Pembrolizumab 200 mg IV q3w
for up to 35 cycles
(n=154)
Chemotherapy (histology-
based) for up to 6 cycles
(n=151)
Until PD or
unacceptable
toxicity
Stratified by ECOG PS (0 vs 1),
histology (squamous vs
nonsquamous), and enrollment
region
Until PD (crossover
to pembrolizumab
allowed)

15. Increased PFS With Pembrolizumab in PD-L1 High
HR = hazard ratio; CI = confidence interval.
Reck et al, 2016.
KEYNOTE-024
PFS(%)
100
80
60
40
20
0
Months
180 3 6 9 12 15
Pembrolizumab
(n=154)
Chemotherapy
(n=151)
Median PFS, months 10.3 6.0
HR (95% CI) 0.50 (0.37-0.68); P<0.001

16. Increased OS With Pembrolizumab in PD-L1 High
NR = not reached.
Reck et al, 2016.
KEYNOTE-024
Pembrolizumab
(n=154)
Chemotherapy
(n=151)
Median OS NR NR
HR (95% CI) 0.60 (0.41-0.89); P=0.005

17. First-Line Nivolumab Versus Chemotherapy
Primary end point: PFS (≥5% PD-L1 positive)
Secondary end points: PFS (≥1% PD-L1 positive), ORR, OS
Pts with stage IV/recurrent
NSCLC, no previous systemic
therapy, no actionable
EGFR/ALK mutations,
PD-L1 expression ≥1%
(N=541)
Nivolumab 3 mg/kg IV q2w
(n=271)
Chemotherapy (histology-
based) for up to 6 cycles
(n=270)
Until PD or
unacceptable
toxicity
Stratified by PD-L1 expression (<5% vs ≥5%)
and histology (squamous vs nonsquamous)
Until PD (crossover
to nivolumab
allowed)
q2w = every two weeks.
Socinski et al, 2016.

18. Patients Positive ≥5%: No PFS Benefit With Nivolumab
No = number.
Socinski et al, 2016.
CheckMate-026

19. Treatment With Pembrolizumab
DCB = durable clinical benefit; NDB = no durable benefit.
Rizvi et al, 2015.
More Mutations/Tumor Predicted Durable Clinical Benefit

20. Treatment with Pembrolizumab
Rizvi et al, 2015.
More Mutations/Tumor Predicted Longer PFS

21. Exploratory Subgroup Analyses of Outcomes
Carbone et al, 2017.
High Tumor Mutation Burden

22. Exploratory Subgroup Analyses of Outcomes
Carbone et al, 2017.
Low or Medium Tumor Mutation Burden

23. First-Line NSCLC: PD-L1–High
NCCN, 2019.
The personalized therapy choice for PD-L1–high tumors in the
absence of severe cancer symptoms or contraindications is
pembrolizumab
There is no data in PD-L1 >50% comparing pembrolizumab to pembrolizumab +
chemotherapy

24. First-Line Therapy:
PD-L1–Low/Negative Tumors

25. Case Study 1 (cont.)
Instead, the tumor is PD-L1 low (1%), KRAS mutant, and TMB 14 mut/Mb
on FoundationOne. What do you suggest?
a. Pembrolizumab
b. Carboplatin + pemetrexed + pembrolizumab
c. Carboplatin + pemetrexed without pembrolizumab due to increased AEs
of combination
d. Nivolumab monotherapy
e. Ipilimumab + nivolumab

26. Pembrolizumab vs Platinum-Based Chemo
CNS = central nervous system; AUC = area under the concentration; mo = months.
Lopes et al, 2018.
First-Line Advanced NSCLC TPS ≥1%

27. Pembrolizumab vs Platinum-Based Chemo
Lopes et al, 2018.
First-Line Advanced NSCLC TPS ≥1% (cont.)
OS: TPS ≥50% OS: TPS ≥1% OS: TPS ≥1% to 49%
(Exploratory Analysis)*

28. KEYNOTE-189: Carboplatin + Pemetrexed +/- Pembrolizumab
aPercentage of tumor cells with membranous PD-L1 staining assessed using the PD-L1 IHC 22C3 pharmDx assay.
bPatients could cross over during the induction or maintenance phases. To be eligible for crossover, PD must have been verified by blinded, independent central radiologic review, and all safety
criteria had to be met.
Gandhi et al, 2018.
• Untreated stage IV
nonsquamous NSCLC
• No sensitizing EGFR or
ALK alteration
• ECOG PS 0 or 1
• Provision of a sample for
PD-L1 assessment
• No symptomatic brain
metastases
• No pneumonitis requiring
systemic steroids
Pembrolizumab 200 mg +
pemetrexed 500 mg/m2 +
carboplatin AUC 5 OR
cisplatin 75 mg/m2
q3w for 4 cycles
Placebo (normal saline) +
pemetrexed 500 mg/m2 +
carboplatin AUC 5 OR
cisplatin 75 mg/m2
q3w for 4 cycles
R
(2:1)
n=410
n=206
Pembrolizumab
200 mg q3w for
up to 31 cycles
+
pemetrexed
500 mg/m2 q3w
Placebo (normal
saline) for up to 31
cycles
+
pemetrexed
500 mg/m2 q3w
• PD-L1 expression
(TPSa <1% vs ≥1%)
• Platinum
(cisplatin vs carboplatin)
• Smoking history
(never vs former/current)
Pembrolizumab
200 mg q3w
for up to 35 cycles
PDb
Stratification
Factors
Key Eligibility
Criteria

29. Response Rate by PD-L1 TPS
32.3% 14.3% 48.4% 20.7% 61.4% 22.9%
0
10
20
30
40
50
60
70
80
90
100
TPS <1% P TPS <1% C TPS 1-49% P TPS 1-49% C TPS ≥50% P TPS ≥50% C
ORR,%(95%CI)
aNominal and one-sided. Data cutoff date: Nov 8, 2017.
RECIST = Response Evaluation Criteria in Solid Tumors; BICR = blinded, independent central review; plat = platinum.
Gandhi et al, 2018.
RECIST v1.1, BICR
Pa = 0.0055
Pa = 0.0001
Pa < 0.0001
Pembro/peme/plat (P)
Placebo/peme/plat (C)

30. Progression-Free Survival by PD-L1
RECIST v1.1
Events
HR
(95% CI) Pa
Pembro/peme/plat 72.4%
0.75
(0.53-1.05)
0.0476
Placebo/peme/plat 85.7%
TPS <1% 19.1%
15.7%
aNominal and one-sided. BICR. Data cutoff date: Nov 8, 2017.
Gandhi et al, 2018.

31. Progression-Free Survival by PD-L1 (cont.)
aNominal and one-sided. BICR. Data cutoff date: Nov 8, 2017.
Gandhi et al, 2018.
RECIST v1.1
TPS 1-49% 37.5%
19.6%
Events
HR
(95% CI) Pa
Pembro/peme/plat 54.7%
0.55
(0.37-0.81)
0.0010
Placebo/peme/plat 75.9%

32. Progression-Free Survival by PD-L1 (cont.)
aNominal and one-sided. BICR. Data cutoff date: Nov 8, 2017.
Gandhi et al, 2018.
RECIST v1.1
TPS ≥50% 44.9%
15.4%
Events
HR
(95% CI) Pa
Pembro/peme/plat 51.5%
0.36
(0.25-0.52)
<0.0001
Placebo/peme/plat 80.0%

33. Progression-Free Survival in Subgroups
Gandhi et al, 2018.
RECIST v1.1
Data cutoff date: Nov 8, 2017.

34. Progression-Free Survival in Subgroups (cont.)
Gandhi et al, 2018.
RECIST v1.1
Data cutoff date: Nov 8, 2017.

35. Overall Survival, ITT
aNominal and one-sided. Data cutoff date: Nov 8, 2017.
ITT = intention to treat; NE = not estimable.
Gandhi et al, 2018.
Events HR (95% CI) Pa
Pembro/peme/plat 31.0% 0.49
(0.38-0.64) <0.00001
Placebo/peme/plat 52.4% 69.2%
49.4%
Median (95% CI)
NR (NE-NE)
11.3 mo (8.7-15.1)
Pembro/peme/plat
Placebo/peme/plat

36. Overall Survival by PD-L1 TPS
aNominal and one-sided. Data cutoff date: Nov 8, 2017.
Gandhi et al, 2018.
TPS <1%
Events
HR
(95% CI) Pa
Pembro/peme/plat 38.6% 0.59
(0.38-0.92)
0.0095
Placebo/peme/plat 55.6%
61.7%
52.2%
Pembro/peme/plat
Placebo/peme/plat

37. Overall Survival by PD-L1 TPS (cont.)
aNominal and one-sided. Data cutoff date: Nov 8, 2017.
Gandhi et al, 2018.
TPS 1%-49%
71.5%
50.9%
Pembro/peme/plat
Placebo/peme/plat
Events
HR
(95% CI) Pa
Pembro/peme/plat 28.9% 0.55
(0.34-0.90)
0.0081
Placebo/peme/plat 48.3%

38. Overall Survival by PD-L1 TPS (cont.)
aNominal and one-sided. Data cutoff date: Nov 8, 2017.
Gandhi et al, 2018.
TPS ≥50%
Events
HR
(95% CI) Pa
Pembro/peme/plat 25.8% 0.42
(0.26-0.68)
0.0001
Placebo/peme/plat 51.4%
Pembro/peme/plat
Placebo/peme/plat

39. Adverse Events of Interest in the As-Treated Population
Gandhi et al, 2018.

40. Tumor Mutation Burden

41. CheckMate 227 Part 1: Study Design
SQ = squamous; NSQ = nonsquamous; q2w = every 2 weeks; q6w = every 6 weeks.
Hellmann et al, 2018a.
Database lock: January 24, 2018;
Minimum follow-up: 11.2 months
n=1,189
<1% PD-L1
expression
n=550
Nivolumab 3 mg/kg q2w +
ipilimumab 1 mg/kg q6w
n=396
Histology-based
chemotherapy
n=397
Nivolumab 240 mg q2w
n=396
Nivolumab 3 mg/kg q2w +
ipilimumab 1 mg/kg q6w
n=187
Histology-based
chemotherapy
n=186
Nivolumab 360 mg q3w +
histology-based chemotherapy
n=177
R
1:1:1
Key Eligibility Criteria
• Stage IV or recurrent
NSCLC
• No prior systemic therapy
• No known sensitizing
EGFR/ALK alterations
• ECOG PS 0–1
Stratified by SQ vs NSQ
R
1:1:1
≥1% PD-L1
expression
Nivolumab +
ipilimumab
n=396
Chemotherapy
n=397
Patients for PD-L1
co-primary analysis
Co-primary end points: nivolumab +
ipilimumab vs chemotherapy
• OS in PD-L1–selected populations
• PFS in TMB-selected populations
Nivolumab +
ipilimumab
n=139
Chemotherapy
n=160
Patients for TMB
co-primary analysis

42. TMB and Tumor PD-L1 Expression
Hellmann et al, 2018a.
Distinct and Independent Populations of NSCLC
Tumor PD-L1 expressionTMB and Tumor PD-L1 Expression
PD-L1 expression (%)
TMB(numberofmutations/Mb)
0
20
40
60
80
100
160
120
140
0 20 40 60 80 100
TMB ≥10 mut/Mb
TMB <10 mut/Mb
<1%
29%
≥1%
71%
<1%
29%
≥1%
71%
<1%
29%
≥1%
71%

43. Co-Primary End Point: PFS With Nivo/Ipi vs Chemo
Ipi = ipilumumab.
Hellmann et al, 2018a.
Patients With High TMB (≥10 mut/Mb)
Nivo + Ipi
(n=139)
Chemo
(n=160)
Median PFS, mo 7.2 5.4
HR
97.5% CI
0.58
0.41, 0.81
P=0.0002
In patients withTMB <10 mut/Mb treated with
nivolumab/ipilumumab versus chemotherapy,
the HR was 1.07 (95% CI: 0.84, 1.35)

44. Patients With High TMB (≥10 mut/Mb)
CR = complete response; PR = partial response.
Hellmann et al, 2018b.
Overall Response Rate
Median time to response:
2.7 months with nivolumab + ipilimumab
1.5 months with chemotherapy
41.7
26.3

45. Patients With High TMB (≥10 mut/Mb)
DOR = duration of response.
Hellman et al, 2018b.
Duration of Response
Nivo + Ipi
(n=63)
Chemo
(n=43)
Median DOR, mo
(95% CI)
NR
(12.2, NR)
5.4
(4.2, 6.9)

46. CheckMate 227: Adverse Events
Hellmann et al, 2018a.

47. Is There a Case for TMB?
The bottom line on TMB:
Biomarker testing still not standardized
OS data failed to support an indication for ipilimumab + nivolumab
The future of TMB?
Blood-based TMB being used as a biomarker for first-line durvalumab
+ tremelimumab phase 3 studies, more to come
Clinicaltrials.gov, 2019.

48. Targeting Angiogenesis

49. Agents Targeting the VEGF Pathway
VEGF = vascular endothelial growth factor; VEGFR = VEGF receptor.
Podar & Anderson, 2005.
VEGFR-2VEGFR-1
P
PP
PP
PP
P
Endothelial cell Small-moleculeVEGFR
inhibitors
Anti-VEGFR
antibodies
(ramucirumab)
VEGF
Anti-VEGF
antibodies
(bevacizumab)
Soluble
VEGFRs
(VEGF-Trap)

50. IMpower150
Socinski et al, 2018a.
Carboplatin/Paclitaxel +/- Bevacizumab +/- Atezolizumab
Arm A
Atezolizumab + carboplatin/paclitaxel
4 or 6 cycles
Atezolizumab
Arm C (control)
Carboplatin/paclitaxel
+ bevacizumab
4 or 6 cycles
Bevacizumab
Survivalfollow-up
Stage IV or
recurrent metastatic
nonsquamous NSCLC
Chemotherapy-naive
Tumor tissue available for
biomarker testing
Any PD-L1 IHC status
Stratification factors:
• Sex
• PD-L1 IHC expression
• Liver metastases
N=1,202
R
1:1:1
Arm B
Atezolizumab + carboplatin/paclitaxel
+ bevacizumab
4 or 6 cycles
Atezolizumab
+
bevacizumab
Maintenance therapy
(no crossover permitted)
Treated with
atezolizumab until PD
by RECIST v1.1
or loss of clinical
benefit
AND/OR
Treated with
bevacizumab until PD
by RECIST v1.1

51. IMpower150 (cont.)
Socinski et al, 2018a.
Carboplatin/Paclitaxel +/- Bevacizumab +/- Atezolizumab
Patients with a sensitizing EGFR mutation or ALK translocation must have
disease progression or intolerance of treatment with one or more approved
targeted therapies:
Atezolizumab: 1,200 mg IV q3w
Carboplatin: AUC 6 IV q3w
Paclitaxel: 200 mg/m2 IV q3w
Bevacizumab: 15 mg/kg IV q3w

52. IMpower150 (cont.)
WT = wild type; CXCL9 = chemokine (C-X-C motif) ligand 9; IFNγ = interferon gamma.
Socinski et al, 2018a.
Carboplatin/Paclitaxel +/- Bevacizumab +/- Atezolizumab
WT refers to patients without EGFR or ALK genetic alterations
The T-effector (Teff) gene signature is defined by expression of PD-L1,
CXCL9, and IFNγ and is a surrogate of both PD-L1 IHC expression and pre-
existing immunity

53. IMpower150: Overall Survival (Intent-to-Treat)
aUnstratified HR. Data cutoff: January 22, 2018
Bev = bevacizumab; CP = carboplatin/paclitaxel.
Socinski et al, 2018b.
Clinically meaningful survival benefit observed with atezolizumab + bevacizumab + chemo vs
bevacizumab + chemo in all patients
Landmark
OS, %
Arm B:
Atezo + Bev + CP
Arm C:
Bev + CP
12-month 68% 61%
18-month 54% 42%
24-month 45% 36%
HRa, 0.77
(95% CI: 0.63, 0.93)
Median follow-up: ~20 mo

54. Atezolizumab + Carboplatin/Paclitaxel + Bevacizumab
Statistically significant and clinically
meaningful OS benefit with atezolizumab
+ bevacizumab + chemotherapy vs
bevacizumab + chemotherapy was
observed
aStratified HR. Data cutoff: January 22, 2018.
Socinski et al, 2018a.
IMpower150: OS in the ITT-WT (Arm B vs Arm C)
Landmark
OS, %
Arm B:
Atezo + Bev + CP
Arm C:
Bev + CP
12-month 67% 61%
18-month 53% 41%
24-month 43% 34%
HRa, 0.780
(95% CI: 0.636, 0.956)
P=0.0164
Median follow-up: ~20 mo

55. IMpower150: Adverse Events
ABCP = atezolizumab/bevacizumab/carboplatin/paclitaxel; BCP = bevacizumab/carboplatin/paclitaxel.
Socinski et al, 2018a.

56. IMpower150: Adverse Events (cont.)
Socinski et al, 2018a.

57. First-Line NSCLC
Image courtesy of Jamie Chaft, MD.
NCCN, 2019.
2019
Test for EGFR,ALK, ROS1, BRAF,
and PD-L1
Targeted
therapy
Carbo + pemetrexed
+/- pembrolizumab
or ? pembro
Newly
diagnosed
Pembrolizumab
Best supportive care
Platinum-doublet
chemo +/- pembrolizumab
+/- bevacizumab
PD-L1–high

58. Second-Line Treatment
(Driver Negative)

59. Case Study 2
COPD = chronic obstructive pulmonary disease.
72-year-old woman with COPD, diagnosed with advanced lung
adenocarcinoma involving the bilateral lungs and lymph nodes. Her tumor is
driver negative and PD-L1 low
She is treated with carboplatin, pemetrexed, and pembrolizumab with
stable disease for 6 months
She develops hip pain and is found to have new bone metastases

60. Case Study 2 (cont.)
After hip RT, how would you treat this patient?
a. Ipilimumab + nivolumab
b. Docetaxel + ramucirumab
c. Paclitaxel + bevacizumab
d. Single-agent chemotherapy
RT = radiotherapy.

61. REVEL: Study Design
Y = yes; N = no.
Garon et al, 2014.
Ramucirumab in Second-Line
Inclusion Criteria
• Stage 4 NSCLC progressing on or after 1
platinum-based regimen
• Prior bevacizumab allowed
• Squamous or nonsquamous histologies
• ECOG PS 0/1
Stratification
• Geography (East Asia or other)
• ECOG PS
• Sex
• Prior maintenance therapy (Y or N)
R
A
N
D
O
M
I
Z
E
1:1
S
C
R
E
E
N
Ramucirumab 10 mg/kg
+
Docetaxel 75 mg/m2
n=628
Placebo
+
Docetaxel 75 mg/m2
n=625
Every
3 weeks
Treatment until
disease
progression or
unacceptable
toxicity
N=1,253
End Points
Primary Overall survival
Secondary Progression-free survival, overall response rate, safety, patient-reported outcomes
Study Design:
Phase 3 randomized,
multisite study of
ramucirumab or placebo
plus docetaxel following
progression on or after a
platinum-based regimen

62. REVEL: Prior Anti-Cancer Therapy
Garon et al, 2014.
SystemicTherapy
Ramucirumab + Docetaxel
(n=628)
Placebo + Docetaxel
(n=625)
n (%) n (%)
Patients with at least 1 prior therapy 626 (99.7) 625 (100.0)
Platinums 623 (99.2) 622 (99.5)
Pemetrexed 231 (36.8) 247 (39.5)
Gemcitabine 156 (24.8) 151 (24.2)
Taxanes 153 (24.4) 152 (24.3)
Vinca alkaloids 74 (11.8) 68 (10.9)
Topoisomerase inhibitors 42 (6.7) 34 (5.4)
Alkylating agents 2 (0.3) 2 (0.3)
Bevacizumab 89 (14.2) 92 (14.7)
Aflibercept – – 1 (0.2)
Tyrosine kinase inhibitors 23 (3.7) 25 (4.0)
EGFR antibodies 15 (2.4) 11 (1.8)
Investigational drug 34 (5.4) 33 (5.3)
Other 13 (2.1) 15 (2.4)

63. REVEL: Docetaxel +/- Ramucirumab
Garon et al, 2014.
Progression-Free Survival

64. TEAEsa, %
Ramucirumab + Docetaxel
(n=627)
Placebo + Docetaxel
(n=618)
% Any Grade % Grade ≥3 % Any Grade % Grade ≥3
Any 98 79 95 71
Fatigue 55 14 49 10
Decreased appetite 29 2 25 1
Diarrhea 32 5 27 3
Nausea 27 1 27 1
Alopecia 26 – 25 –
Stomatitis 23 4 13 2
Neuropathy 23 3 20 2
Dyspnea 22 4 24 8
Cough 21 <1 20 1
Pyrexia 17 <1 13 <1
Peripheral edema 16 – 8 <1
REVEL: Docetaxel +/- Ramucirumab
aOccurring in ≥10% of patients in either group.
Garon et al, 2014.
Treatment-EmergentAdverse Events (TEAE)

65. REVEL: Docetaxel +/- Ramucirumab
Garon et al, 2014.
Overall Survival (ITT)

66. REVEL: Overall Survival—Subset Analysis
SD = stable disease.
Garon et al, 2014.

67. Key Takeaways
Biomarker testing for PD-L1 and oncogene driver mutations is essential
in NSCLC
Immunotherapy is superior to chemotherapy in patients with PD-L1–high
tumors
Chemotherapy and immunotherapy is better than chemotherapy in PD-
L1–low/negative tumors
Anti-angiogenesis agents have a role in first- and second-line
management for some patients

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