Maximising Clinical Benefit from TKIs in the Treatment of ... · Maximising Clinical Benefit from...

Maximising Clinical Benefit from TKIs in the Treatment of

Advanced NSCLC

2017 WCLC- PACIFICO Yokohama Convention Center

16 October, 2017

BI symposium

Meeting Welcome and Introductions


Tetsuya Mitsudomi, MD, PhD

Kindai University Faculty of Medicine

Osaka-Sayama, Japan

3

Faculty Disclosure

• Honoraria and Advisory boards: AstraZeneca, Boehringer Ingelheim, Chugai,

Pfizer, MSD, and Ono

• Grant support: Boehringer Ingelheim, Chugai, Pfizer, and Ono.

4

Agenda

Time Topic Speaker

12:45 – 12:50 Meeting Welcome and Introductions Tetsuya Mitsudomi

(Japan)

12:50 – 13:10 Emerging Algorithm for Optimal Sequencing of EGFR TKIs in EGFR Mutation-

Positive NSCLC

Keunchil Park

(S. Korea)

13:10 – 13:30 Efficacy of EGFR TKIs in NSCLC Patients with Uncommon EGFR Mutations Terufumi Kato

(Japan)

13:30 – 13:50 Considerations for Choosing TKIs for Squamous NSCLC in the Era of

Immunotherapy: Which Patients Could Benefit?

Barbara Melosky

(Canada)

13:50 – 14:10

Panel Discussion

Carrying the Data into the Clinic: TKI Sequencing Decisions for EGFR Mutation-

Positive NSCLC Patients

All Faculty

Moderator:

Tetsuya Mitsudomi

14:10 – 14:15 Meeting Close Tetsuya Mitsudomi

5

Faculty

Chair: Tetsuya Mitsudomi, MD, PhD

Kindai University Faculty of Medicine

Osaka-Sayama, Japan

Terufumi Kato, MD

Kanagawa Cardiovascular and

Respiratory Center

Tokyo, Japan

Keunchil Park, MD, PhD

Samsung Medical Center,

Sungkyunkwan University School of Medicine

Seoul, Korea

Barbara Melosky, MD, FRCPC

University of British Columbia,

British Columbia Cancer Agency

Vancouver, BC

Emerging Algorithm for Optimal Sequencing of EGFR TKIs in

EGFR Mutation‒Positive NSCLC 2017 WCLC- PACIFICO Yokohama Convention Center

Keunchil Park, MD, PhD

Samsung Medical Center,

Sungkyunkwan University School of Medicine

BI symposium

7

Faculty Disclosure

• Consulting or Advisory Role: Astellas Pharma; AstraZeneca; Boehringer

Ingelheim; Clovis Oncology; Hanmi; Kyowa Hakko Kirin; Lilly; Novartis; Ono

Pharmaceutical; Roche

• Speakers' Bureau: Boehringer Ingelheim

• Research Funding: AstraZeneca

8

Key Factors in First-line EGFR

TKI Selection

Sequence makes survival

Not all TKIs are equal

Efficacy Drug-drug

interactions

Adverse event profile

9


TKI Selection



Efficacy Drug-drug

interactions


10

The Family of EGFR TKIs

Liao et al. Curr Opin Oncol. 2015;27:94.

Wild-type EGFR

Intrinsic mutant EGFR

Acquired T790M EGFR

2nd-generation TKI

3rd-generation TKI

K K K K K K

K Kinase domain

Activity range

Activity

• Reversible binding to wild-type and mutant EGFR

• Inactive on T790M mutant

• Irreversible covalent binding to EGFR, ErbB2 and ErbB4 to inhibit

all ErbB Family signalling • Broader activity to overcome EGFR TKI‒resistant mutations

• Specificity for EGFR T790M mutant; EGFR

wild-type sparing • Irreversible covalent binding to mutant EGFR

EGFR inhibition

ErbB Family blockade

EGFR mutant‒specific inhibitor

1st-generation TKI Activity range Erlotinib

Gefitinib

Afatinib

Dacomitinib

Osimertinib

K

ErbB heterodimers (eg, Her2: ErbB3)

Range

11

Activity of First-, Second-, and Third-Generation EGFR

TKIs Against EGFR Mutations

Li et al. Oncogene. 2008;27:4702; Cross et al. Cancer Discov. 2014;4:1046; Hirano et al. Oncotarget. 2015;6:38789.

IC50 = half-maximal inhibitory concentration.

EGFR mutant: L858R, exon 19 del Wild-type EGFR T790M

Gefitinib Afatinib Osimertinib

EGFRm

EGFRm

EGFRm

Wild-type

Wild-type

Wild-type

T790M

T790M

100×

10×

1×

T790M

IC5

0 (

nM

)

12


TKI Selection



Efficacy Drug-drug

interactions


13

First- and Second-Generation EGFR TKIs Are Standard for

First-line Treatment of NSCLC With Common EGFR Mutations

• Better PFS vs platinum-based chemotherapy

Chen et al. Ann Oncol. 2013;24:1615; Gefitinib Summary of Product Characteristics 2010; Han et al. J Clin Oncol. 2012;30:1122; Maemondo et al. N Engl J Med.

2010;362:2380; Mok et al. N Engl J Med. 2009;361:947; Mitsudomi et al. Lancet Oncol. 2010;11:121; Rosell et al. Lancet Oncol. 2012;13:239; Sequist et al. J Clin Oncol.

2013;31:3327; Wu et al. Lancet Oncol. 2014;15:213; Wu et al. Ann Oncol. 2015;26:1883; Zhou et al. Lancet Oncol. 2011;8:735.

aPFS not reported for common mutations only.

NSCLC = non‒small cell lung cancer.

Gefitiniba Erlotinib Platinum-based chemotherapy

[VALUE] 11

13.1

9.2

10.8

9.7a

13.6

11

5.2 5.5 4.6

[VALUE] 5.4

[VALUE]a 6.9

5.6

Afatinib

month

s

EURTAC ENSURE OPTIMAL WJTOG NJE002 IPASS LL3 LL6 EURTAC ENSURE OPTIMAL WJTOG NJE002 IPASS LL3 LL6

14

First- and Second-Generation EGFR TKIs Are Not Equal:

Response Rate and PFS in LUX-Lung 7

LUX-Lung 7: Afatinib vs Gefitinib

Park et al. Lancet Oncol. 2016;17:577; Corral et al. ELCC 2017. Abstract 93PD.

P=0.002

73% 75%

69%

56%

66%

42%

0%

20%

40%

60%

80%

ITT Del19 L858R

Re

sp

on

se

ra

te (

%)

P=0.150 P=0.003

Gefitinib Afatinib P

FS

(%

)

Time (months)

160 142 112 94 67 47 34 27 21 13 6 3 1 0 0

159 132 106 83 52 22 14 9 7 5 3 3 1 1 0

Afatinib

Gefitinib

27%*

18%†

15%

100

80

60

40

20

0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42

8%

Afatinib

(n=160)

Gefitinib

(n=159)

Median, mo 11.0 10.9

HR (95% CI)

P value

0.73 (0.57-0.95)

P=0.017

15

First- and Second-Generation EGFR TKIs Are Not Equal:

PFS in ARCHER 1050

ARCHER 1050: Dacomitinib vs Gefitinib (excluding CNS metastases)

Mok et al. ASCO 2017. Abstract LBA9007.

CNS = central nervous system; ITT = intent-to-treat; CI, confidence interval.

PFS: Blinded Independent Review (ITT population)

Months

0

0

0

0

6

1

20

7

73

34 106

69

154

155

227

225

No. at risk:

Dacomitinib

Gefitinib

Pro

ba

bilit

y o

f P

FS

1.0

0.8

0.6

0.4

0.2

0.0

0 6 12 18 24 30 42 36

++ Censored

PFS rate

30.6% vs 9.6% Dacomitinib

Gefitinib

Dacomitinib

(n=227)

Gefitinib

(n=225)

Number of events, n (%) 136 (59.9%) 179 (79.6%)

Median PFS (95% CI) 14.7

(11.1-16.6)

9.2

(9.1-11.0)

HR (95% CI)

P value

0.59 (0.47-0.74)

P=0.0001

16

First and Third-Generation EGFR TKIs Are Not Equal:

PFS in FLAURA

Ramalingam et al. ESMO 2017. Abstract LBA2.

DCO: 12 Jun 2017.

Tick marks indicate censored data. aFor statistical significance, P<0.0015, determined by O’Brien planning approach, was required.

OS = overall survival; SoC = standard of care; NS = not significant; DCO = data cut -off.

FLAURA: Osimertinib vs Gefitinib or Erlotinib

Primary Endpoint: PFS (by Investigator Assessment)

Pro

ba

bilit

y o

f P

FS

Time from randomisation (months)

Osimertinib

Gefitinib or Erlotinib

1.0

0.8

0.6

0.4

0.2

0.0 0 3 6 9 12 15 18 21 24 27

279

277

No. at risk:

Osimertinib

SoC 262

239

233

197

210

152 178

107

139

78 71

37

26

10

4

2

0

0

Osimertinib Gefitinib

or Erlotinib

Median PFS,

months (95%

CI)

18.9

(15.2-21.4)

10.2

(9.6-11.1)

HR (95% CI)

P value

0.46 (0.37-0.57)

P<0.0001

17


TKI Selection



Efficacy Drug-drug

interactions


18

Safety

Second- or Third-Generation TKIs vs First-Generation TKIs

1. Park et al. Lancet Oncol. 2016;17:577; 2. Paz-Ares et al. Ann Oncol. 2017;28:270; 3. Mok et al. ASCO 2017. Abstract LBA9007; 4. Ramalingam et al. ESMO 2017. Abstract

LBA2.

LUX-Lung 71,2 ARCHER 10503 FLAURA4

Afatinib

(n=160)

Gefitinib

(n=159)

Dacomitinib

(n=227)

Gefitinib

(n=225)

Osimertinib

(n=279)

Treatment

discontinuation

rate

6.3% 6.3% 9.7% 6.6% 13.0%

(any)

Most common

grade ≥3 AEs

Diarrhoea: 12%

Rash/acne: 9%

Liver enzyme

elevation: 9%

Rash/acne: 3%

Acne: 14%

Diarrhoea: 9%

Paronychia: 8%

Liver enzyme

elevation: 9%

Paronychia: 1%

Diarrhoea: 2%

Decreased

appetite: 3%

19

Dose Reduction of Afatinib Reduced Drug-Related AEs

Without Compromising Efficacy

Hirsch V, et al. ASCO 2016 poster presentation: 369.

PFS = progression-free survival; HR = hazard ratio; CI = confidence interval.

Treatment-Related AEs in Patients Who

Had a Dose Reduction From 40 mg (n=63)

100.0 95.2

81.0

60.3

28.6

[VALUE]

25.4 [VALUE] 7.9 3.2 0

20

40

60

80

100

Any Diarrhoea Rash/acne Stomatitis Nail effect

pa

tie

nts

(%

)

90.5

61.9 52.4

27.0 33.3

23.8 9.5 3.2 3.2 0.0

0

20

40

60

80

100

Any Diarrhoea Rash/acne Stomatitis Nail effect

pa

tie

nts

(%

)

Be

fore

re

du

cti

on

(≥40 m

g),

Aft

er

red

ucti

on

(<40 m

g),

PFS in Patients Who Received a Dose Reduction

Within the First 6 Months of Treatment

Est

ima

ted

PF

S p

rob

ab

ilit

y

1.0

0.8

0.6

0.4

0.2

0

0 3 6 9 12 15 18 21 24 27 30 33 36 39

Months

45 34 28 22 15 11 10 9 7 3 1 0 0 47

113 97 78 66 45 32 23 17 12 6 3 2 1 0

No. at risk:

<40 mg

≥40 mg

<40 mg in

First 6 Months

(n=47)

≥40 mg for

First 6

Months

(n=113)


HR (95% CI)

P value

1.34 (0.90-2.00)

P=0.1440

All grade Grade ≥3

20


TKI Selection



Efficacy Drug-drug

interactions


21

DDIs of First-, Second-, and Third-Generation EGFR TKIs

Cross et al. Cancer Discov. 2014;4:1046; Li et al. Oncogene. 2008;27:4702; Peters et al. Cancer Treat Rev. 2014;40:917; TAGRISSO Prescribing Information. March 2017.

Enzymes Involved in the Metabolism of Oral EGFR TKIs

May Inhibit May Induce Drug

Metabolised by CYP Enzymes

3A4 3A5 2D6 1A1 1A2 1B1 2C8 2C9

Gefitinib +++ ++ +++ ++ + -

CYP2C19 (w)

CYP2D6 (w) UGT1A9, BRCP

Erlotinib +++ +++ + + ++ + + +

CYP3A4 (m)

CYP2C8 (m) CYP1A1 (s)

UGT1A1 (s)

CYP1A1

CYP1A2

Afatinib - - - - - - - - - -

Dacomitinib ++ ++ + CYP2D6 (s)

Osimertinib +++ +++ - - - - - - BCRP

CYP3A4

CYP1A2 CYP2C

DDI = drug-drug interaction; CYP = cytochrome P450 enzyme; BCRP = breast cancer resistance protein; UGT = UDP-glycosyltransferase.

22


TKI Selection



Efficacy Drug-drug

interactions


23

OS with Afatinib in EGFR-Mutant NSCLC

Yang et al. Lancet Oncol. 2015;16:141.

Common Mutations (del19/L858R) (n=307)

aOnly 6 patients in the afatinib arm w ere treated with osimertinib because of lack of availibility (trial recruitment w as from August 2009 to February 2011).

NSCLC = non‒small cell lung cancer.

0

0.2

0.4

0.6

0.8

1.0

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51

Months

197 188 101 90 58 9 203

104 98 92 40 35 26 5

No. at risk:

Af atinib

Cis/Pem

181

86

171

81

162

71

143

63

133

55

121

52

108

47

49

20

32

10

1

1

0

0

No. at risk:

Af atinib

Cis/Pem

Es

tim

ate

d O

S p

rob

ab

ilit

y

Afatinib

Cis/Pem

Common mutation

Afatiniba

(n=203)

Cis/Pem

(n=104)


HR (95% CI) 0.78 (0.58-1.06)

24

Molecular Mechanisms of Acquired Resistance to

First-/Second-Generation EGFR TKIs

Yu HA et al. Clin Cancer Res. 2013;19:2240.

• 155 EGFR mutant NSCLC,

acquired resistance after TKI

• Molecular analyses on

re-biopsy specimen

T790M

(60%)

Unknown (18%)

HER2 (8%)

MET amplification (3%)

Small cell+MET (1%)

Small cell (1%)

Small cell+T790M (2%)

MET+T790M (3%)

HER2 T790M (4%)

25

OS in Patients Treated With Third-Generation TKIs

Subsequently in LUX-Lung 7

Corral et al. ELCC 2017. Abstract 93PD.

NE = not estimable.

20%/17% who discontinued afatinib/gefitinib received third-generation TKIs (osimertinib, olmutinib,

rociletinib)

Months

Es

tim

ate

d O

S p

rob

ab

ilit

y

0.8

1.0

0.6

0.4

0.2

0

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57

30

26

No. at risk:

Afatinib

Gefitinib 30

26

30

25

30

25

30

25

30

24

29

23

29

23

29

23

29

22

28

22

28

22

26

20

21

17

17

17

14

10

8

4

1

1

0

0

Afatinib

(n=30)

Gefitinib

(n=26)

Median, mo NE 48.3

HR (95% CI)

P value

0.49 (0.20-1.19)

P=0.107

26

Treatment Sequences in EGFR-Mutant NSCLC After

First-line EGFR TKI

1st-/2nd-generation TKI

Osimertinib T790M +

T790M

-

Other

Chemotherapy 1st-/2nd-generation TKI

MET/HER2 inhibitor

Chemotherapy

Except if molecular target

Osimertinib Chemotherapy

Except if molecular target

NEED MATURE OS AND TREATMENT SEQUENCES FROM AURA3 and FLAURA (med PFS = 18.9 months)

27


TKI Selection



Efficacy Drug-drug

interactions


For more information about other BI events and collaborations, please visit www.inOncology.com

http://www.inoncology.com/

Efficacy of EGFR TKIs in Patients With NSCLC With Uncommon

EGFR Mutations 2017 WCLC- PACIFICO Yokohama Convention Center

Terufumi Kato, MD

Kanagawa Cancer Center,Yokohama, Japan

BI Symposium

30

Faculty Disclosure

• Honoraria: AstraZeneca; Boehringer Ingelheim; Chugai Pharma; Kyowa

Hakko Kirin; Lilly; Ono Pharmaceutical; Pfizer; Roche; Taiho Pharmaceutical

• Consulting or Advisory Role: AstraZeneca; Nippon Boehringer Ingelheim;

Ono Pharmaceutical

• Research Funding: Abbvie; Astellas Pharma; AstraZeneca; Bristol-Myers

Squibb; Chugai Pharma; Daiichi Sankyo; Kyowa Hakko Kirin; Lilly; Merck

Sharp & Dohme; Nippon Boehringer Ingelheim; PAREXEL; Pfizer; Quintiles;

Shionogi Pharma; Taiho Pharmaceutical; Takeda; Yakult Honsha

31

EGFR Mutations in NSCLC

Mitsudomi et al., Cancer Science, 2007

Mitsudomi et al., Cancer Science, 2007

EGF binding EGF binding TM Tyrosine kinase Autophosphorylation

Exon 2 5 7 13 16 17 18-21 22-24 28

68

8

72

8

72

9

76

1 7

62

82

3

82

4

87

5

Exon 18 (nucleotide binding loop) Exon 19 Exon 20

Exon 21 (activation loop)

Ex19Del L858R

G719X L861Q Ex20 Ins

32

Common or Uncommon/Non-classical (N=1,632)

Shen et al. Lung Cancer. 2017;110:56.

Single, uncommon/non-classical mutations

or insertion: 8%

Exon 21 single 1%

Exon 20 single 1% insertions 3%

Exon 19 single 0.4% Exon 18 single 3%

Uncommon/non-classical mutation with Del19/L858R: 6%

Complex uncommon/non-classical, without Del19 and L858R: 2%

Del19

(n=354) 42%

Ex21

L858R (n=356)

42%

33

• Irreversible second- and third-generation TKIs overcome resistance induced by

uncommon secondary mutations

In Vitro Activity of First-, Second-, and Third-Generation TKIs

Against Uncommon EGFR Mutations

Chiba M et al. BMC Cancer. 2017;17:281.

Gefitinib

Erlotinib

Afatinib

Dacomitinib

Osimertinib IC50 (

nM

)

10000

0

5

10

15

20

25

30

35

40

45

50

L858R L858R/L747S L858R/D761Y L858R/T854A L858R/T790M

34

In Vitro Activity of First-, Second-, and Third-Generation

TKIs Against Uncommon EGFR Mutations • In separate assays, first- and third-generation TKIs demonstrated reduced activity against cell lines harbouring

uncommon mutations, whereas the response to afatinib was similar across cell lines

1. Saxon et al. J Thorac Oncol. 2017;12:884; 2. Banno et al. Cancer Sci. 2016;107:1134.

TKI = tyrosine kinase inhibitor; IC50 = 50% inhibitory concentration.

1 1 1

20

2.5 3.6

32

3.5

20

0

10

20

30

40

IC50 r

ati

o r

ela

tiv

e

to L

85

8R

L861Q and S768I2

L858R L861Q S768I L858R L861Q S768I L858R L861Q S768I

Erlotinib Afatinib Osimertinib

125

100

75

50

25

0 0 0.001 10 1 0.1 0.01

µM

Ce

ll v

iab

ilit

y (%

)

Afatinib

Gefitinib

Osimertinib

125

100

75

50

25

0 0 0.001 10 1 0.1 0.01

µM

Ce

ll v

iab

ilit

y (%

)

L858M/L861Q1

L858R

Afatinib

Gefitinib

Osimertinib

L858M/L861Q

35

EGFR Exon 18 Mutations in Lung Cancer:

Molecular Predictors of Augmented Sensitivity to Afatinib as

Compared with First- or Third-Generation TKIs

• Among 1,402 EGFR mutations, Del19, L858R, and Ins20 were detected in 40%, 47%, and 4%, respectively.

Exon 18 mutations, including G719X, E709X, and Del18, were present in 3.2%

• Patients with lung cancers harbouring G719X exhibited higher response rate to afatinib (80%) than to 1G TKIs

(35%–56%)

Kobayashi Y et al. CCR 2015.

IC90s

of

EG

FR

-TK

Is

in T

ran

sfe

cte

d

Ba

/F3 C

ell

s (n

mo

l/L

)

104

103

102

101

100

10–1 Gefitinib Erlotinib Afatinib Dacomitinib AZD9291

882

187 213

7

9,350

884

215 167

6

>10,000

448*

2,717

69

1.7

0.7 0.9

0.3

>100

29 16

166

6

1.6

>1,000

3,078

400*

1.1

53 62

93

Del 18

E709K

G719A

Del 19

WT

Ctrough

Del 19 40% (n=563)

Ins 20 4% (n=63)

Others 5% (n=71)

Exon 18 3% (n=45)

L858R 47% (n=660)

G719A (n=22)

G719S (n=9)

G719C (n=8)

G719R (n=1)

G719V (n=1)

E709H + G719C (n=1)

Del E709_T710 ins D (n=3)

*

*

*

36

Case Report: Afatinib in a TKI-Pretreated Patient With

EGFR L858M/L861Q (in cis) • 62-year-old Caucasian female with extensive involvement of a poorly differentiated adenocarcinoma

• Worsening disease with 4 months of erlotinib and 4 months of chemotherapy

• Radiographic response 2 months after initiation of afatinib

• Remained on afatinib, with Grade 1 diarrhoea as her only side effect, for 10 months and continues treatment

Saxon et al. J Thorac Oncol. 2017;12:884.

37

Clinical Data in TKI-Pretreated Patients: Radiographic

Responses After Suboptimal Response to Other EGFR-TKIs

Peled et al. J Thorac Oncol. 2017;12:e81.

Patient With ex19del, T790M, and G724S

C797S

T790M

G724S

ex19del

TP53

Mar-15 Sep-15 Oct-15 Dec-15 Mar-16

2.9

0.1

0.3

6.5

19.5

24.2

33

23.6

33.7

7.8

23.7

15.1

39.6

2.6

45.7

60.1

Cell-free DNA tumor response. Cell-free DNA analysis of total somatic alteration burden detected over five time points and

the EGFR variant-specific results over time reflect responses to changes in matched therapy. TP53, tumor protein p53

Apr-14

Gefitinib

Jun-15

Osimertinib

Sep-15

Osimertinib + Afatinib

Dec-15

Pemetrexed

38

Clinical Data in TKI-Pretreated Patients: Best Response in Patients

With LMD Harbouring Uncommon Mutations

• 3/11 patients with leptomeningeal carcinoma treated with afatinib harboured an uncommon Exon 18

mutation (L719X)

• Median CSF concentration in all 11 patients was 2.88 nM (afatinib’s IC50 for EGFR being 0.5 nM).

PFS and OS in patients harbouring a G719X mutation were 5.6 months (2.0-10.0) and 7.0 months (5.6 ongoing to 13.0)

Tamiya et al. Anticancer Res. 2017;37:4177.

aTreatment continued after data cutoff; bCensored at data cutoff (patient still alive).

LMD = leptomeningeal disease; CSF = cerebrospinal f luid; PFS = progression-free survival; OS = overall survival; NE = Not evaluated; PR = partial response;

PD = progressive disease.

Plasma CSF

Best

Response PFS (Days) OS (Days)

1 146.9 NE PR 309 396

2 192.0 6.0 PD 61 212

3 767.6 0.8 PR 171a 171b

Concentration of Afatinib in Plasma and CSF, Penetration Rate, and Efficacy in Patients With EGFR Mutation-Positive NSCLC With LMD

Concentration (nM)

39

Clinical Data in TKI-Pretreated Patients:

Time to Treatment Failure With Afatinib • 66 uncommon mutations were reported (18.4% of all known EGFR mutations in the compassionate-use programme)

– Majority of patients (67%) received afatinib as third- or fourth-line treatment, with median treatment duration of 3.6 months

• No significant difference between median TTF for patients with uncommon/non-classical mutations (3.6 months) compared

with those with Del19 (4.6 months) or L858R (5.8 months) mutations

Heigener et al. Oncologist. 2015;20:1167.

TTF = time to treatment failure.

Distribution of the 60 Rare

EGFR Mutations (N=60)

Exon 18

substitution, 1, 2%

Exon 19

insertion/deletion, 2, 3%

Exon 19 substitution, 4,

7%

Exon 20 insertion, 3, 5%

T790M, 1, 2%

Exon 21 substitution, 4,

7%

Complex mutations

incl. T790M, 29

48%

G719X, 7,

11%

Complex

mutations, 9

15%

100

75

50

25

0 0 6 12 18 24 30

Months

Tre

atm

en

t p

rob

ab

ilit

y (

%) Del19

L858R

Uncommon

40

First-line Clinical Data: Retrospective Analysis of PFS in

57 Patients Treated With Afatinib or First-Generation TKIs • In all mutation groups analysed, the afatinib group

exhibited longer median PFS compared with first-generation TKIs

– Entire uncommon mutations cohort, except exon

20 insertionsa: 11.0 mo vs 3.6 mo

– G719X, S768I, or L861Q: 18.3 mo vs 2.6 mo

– Uncommon mutations with Del19 or L858R:

11.0 mo vs 8.2 mo

Del19+ 18G721D; Del19+ 19L732P; Del19+ 20L792P; Del19+

20S768I + 20V774M; Del19+ 21L858R + 21K860I; 21L858R + 18E709X; 21L858R + 20S768I; 21L858R + 20V786E; 21L858R

+ 20T790M; 21L858R + 20 insertion; 21L858R + 21L833Vl

21L858R + 21K860I; 21L858R + 18G719X +20 insertion

– Uncommon mutation alone or in combination with other

uncommon mutations: 18.3 mo vs 2.8 mo

18I715V; 18K716E; 18V717G; 18G719X; 19L747P;19

insertion; 20A763_Y764 insFQEA; 20S768I; 20G779F;

21L861Q; 18G719X+21L861Q; 18E709X + 18G719X;

18G719X +20S768I; 20T790 M+ 21L861Q; 21M825L +21R831C; 18V703L + 18L707W +18G719X; 18E709X +

18T710S + 18G719X; 19V742F + 19A743 V+ 20H773R

Shen et al. Lung Cancer. 2017;110:56.

CI = confidence interval. aexon 20 insertions (except A763_Y764 insFQEA).

No. at risk 1st TKI 30 12 8 4 2 0 0 0 2nd TKI 21 13 8 5 2 2 1 0


Entire Uncommon Mutations Cohort,

Except Exon 20 Insertions

Uncommon Mutations With

Del19 or L858R

Uncommon Mutation Alone or in Combination

With Other Uncommon Mutations

G719X, S768I, or L861Q 100

90

80

70

60

50

40

30

20

10

0

PF

S (

%)

Months

0 5 10 15 20 25 30 35

Log rank P=0.03

100

90

80

70

60

50

40

30

20

10

0

PF

S (

%)

Months

0 5 10 15 20 25 30 35


100

90

80

70

60

50

40

30

20

10

0 P

FS

(%

)

Months

0 5 10 15 20 25 30 35


100

90

80

70

60

50

40

30

20

10

0

PF

S (

%)

Months

0 5 10 15 20 25 30 35

No. Median (mo) 95% CI 1st TKI 30 3.6 0.1-7.1 2nd TKI 21 11.0 0-22.8

Log rank P=0.24 Log rank P=0.07



No. Median (mo) 95% CI 1st TKI 21 2.8 2.1-3.4 2nd TKI 13 18.3 3.2-33.4

Log rank P=0.12

41

First-line Clinical Data: Prospective Efficacy Assessments

in the LUX-Lung Programme • Of 600 patients given afatinib in LUX-Lung 2/3/6, 75 (12%) patients had uncommon EGFR mutations1

• The LUX-Lung programme provides the largest series of prospective efficacy data in uncommon

mutations1-4

1. Yang et al. Lancet Oncol. 2015;16:830; 2. Passaro et al. J Thorac Dis. 2013;5:383; 3. Katakami et al. J Clin Oncol. 2013;31:3335; 4. Wu et al. Lancet Oncol. 2014;15:213;

5. Yang et al. Lancet Oncol. 2012;13:539; 6. Sequist et el. J Clin Oncol. 2013;31:3327.

aEGFR mutations detected by TheraScreen EGFR29 test. Common: 19 deletions in exon 19 and L858R in exon 21; Uncommon: 3 insertions in exon 20, L861Q, T790M, G719S, G719A and G719C, and S768I.

LUX-Lung 2

Phase 2 (N=129)5

Afatinib

First- and second-line (after chemotherapy)

Direct sequ. (central)

Del19=52 L858R=54

N=23 N=23

LUX-Lung 3

Phase 3 (N=345)6

Afatinib vs Cis/Pem

First-line

EGFR29a (central)

Del19=170 L858R=138

N=37 N=26

LUX-Lung 6

Phase 3 (N=364)4

Afatinib vs Cis/Gem

First-line

EGFR29a (central)

Del19=186 L858R=138

N=40 N=26

Common mutations

Uncommon mutations; treated with afatinib4

Mutation test

Line of treatment

Treatment

42

LUX-Lung 2, 3, and 6: Tumour Shrinkage by Independent

Review (n=67a)

• 3 patients in group 1 achieved complete response

– 1 each with G719X, K739_1744dup6, and L858R+Q709G/V


a8 patients w ere not included because of insuff icient data. bT790M alone.

-100

-80

-60

-40

-20

0

20

40

60

80

100

120

b

b

b

Ma

xim

um

ch

an

ge

fro

m

ba

se

lin

e (

%)

Group 2 (n=14): de novo T790M mutations T790M alone, T790M+Del19, T790M+L858R, T790M+G719X, T790M+L858R+G719X

Group 1 (n=33): point mutations or duplications in exons 18-21 L861Q, G719X, G719X+S768I, G719X+L861Q, E709G or V+L858R, S768I+L858R,

S768I, L861P, P848L, R776H+L858R, L861Q+Del19, K739_1744dup6

Group 3 (n=20): exon 20 insertions

43

LUX-Lung 2, 3, and 6: Response Rate, PFS, and OS by

Independent Review


T790M

(n=14)

Exon 20 ins

(n=23)

Mut/Dup

Exon 18-21

(n=38)

G719X

(n=18)

L861Q

(n=16)

S768I

(n=8)

Response rate

(%) 14.3 8.7 71.1 77.8 56.3 100.0

PFS (mo) 2.9 2.7 10.7 13.8 8.2 14.7

OS (mo) 14.9 9.2 19.4 26.9 17.1 NE

44

Summary

• Afatinib has shown preclinical and clinical activity in TKI-naive and TKI-pretreated

patients with NSCLC harbouring uncommon EGFR mutations

• Activity of afatinib against uncommon EGFR mutations in patients with LMD was also

reported

• Afatinib was especially active in NSCLC tumours harbouring point mutations or

duplications in exons 18-21 (eg, G719X, S768I, L861Q K739_1744dup6, and

L858R+Q709G/V)

• Anecdotal data from erlotinib/gefitinib trials show variable and mainly limited

responses to these EGFR TKIs in patients with NSCLC harbouring uncommon

mutations

• These data could help inform clinical decisions for patients with NSCLC harbouring

uncommon EGFR mutations

45

Yokohama, when sunny, and in later fall…

We are

HERE Just 3 train stops,

or 30 min. walk!

Ocean liner Hikawa maru, Yamashita Park

Considerations for Choosing TKIs for Squamous NSCLC in the

Era of Immunotherapy: Which Patients Could Benefit?


Barbara Melosky

University of British Columbia,

British Columbia Cancer Agency

BI Symposium

48

Faculty Disclosure

• Honoraria: Boehringer Ingelheim, Merck, Eli Lilly, Bristol-Myers Squibb,

Novartis, Pfizer, AstraZeneca

49

Squamous Cell Carcinoma (SqCC) of the Lung

• Squamous histology represents approximately 20–40% of

NSCLC1,2

• SqCC of the lung remains a disease with high unmet need

• SqCC of the lung is associated with poor prognosis3

• Targetable oncogenic alterations are few

• Additional therapeutic options are needed

1. Ho C et al. Curr Oncol. 2015;22:e16 4–e170; 2. Bryant A and Cerfolio RJ. Chest. 2007;132:185–92; 3. Cetin K et al. Clin Epidemiol. 2011;3:139–48.

OS = overall survival; NSCLC = non-small cell lung cancer.

50

Current Treatment Recommendations for Metastatic

SqCC of the Lung

1. Novello S et al. Ann Oncol. 2016;27(suppl 5):v1–v27.

*ESMO guidelines do not recommend maintenance therapy in the treatment of squamous cell carcinoma NSCLC. 1 BSC = Best Standard of Care; EGFR = epidermal growth f actor receptor;

MCBS = Magnitude of Clinical Benef it Scale; NSCLC = non-small cell lung cancer; PD-L = programmed death-ligand; PS = Perf ormance Status; SqCC = squamous cell carcinoma.

Nivolumab (I, A; MCBS 5)

Pembrolizumab if PD-L1>1%

(I, A; MCBS 3 if PD-L1 >1%; MSBC 5 if PD-L1

>50%)

Docetaxel (I, B)

Ramucirumab – docetaxel (I, B; MCBS 2)

Erlotinib (II, C)

Afatinib (I, C; MCBS 1)

PS 3–4

Disease progression

Never or former light

smoker (<15 pack/year)

I) Age

II) PS

<70 years and PS 2

or

>70 years and PS 0–2

PS 0–2

Molecular test

(ALK/EGFR)

Molecular test

positive

Molecular test

negative

Targeted therapy

<70 years and PS 0-1

PS 3–4

BSC (II, B)

4–6 cycles: Cisplatin – gemcitabine (I, A)

Cisplatin – docetaxel (I, A)

Cisplatin – vinorelbine (I, A) Carboplatin – paclitaxel (I, A)

Carboplatin – nab-paclitaxel (I, B) Cisplatin – gemcitabine – necitumumab

(if EGFR expression by IHC)

(I, B; MCBS 1)

4–6 cycles: Carboplatin-based doublets (II, B)

Single-agent chemotherapy

(gemcitabine, vinorelbine or docetaxel) (I,A)

BSC

Stage IV SqCC

51

Overview of Recent Key Phase III ≥ Second-line

Treatment Studies in Patients With SqCC of the Lung

1. Garon E et al. Lancet. 2014;384:665–73; 2. Brahmer J et al. N Engl J Med. 2015;373:123–35; 3. Herbst R et al. Lancet. 2016;387:1540–50; 4. Soria JC et al.

Lancet Oncol. 2015;16:897–907; 5. Rittmeyer A et al. Lancet. 2017;389:255–65.

Trial Treatment Median PFS (mo) HR for PFS Median OS (mo) HR for OS ORR (%)

REVEL1

Ramucirumab + doce vs doce (n=1253) Squamous (n=328)

4.5 vs 3.0 4.2 vs 2.7

0.76* 0.76*

10.5 vs 9.1 9.5 vs 8.2

0.86* 0.88

22.9 vs 13.6* 26.8 vs 10.5*

CheckMate-0172 Nivolumab vs doce All squamous (n=272)

3.5 vs 2.8

0.62*

9.2 vs 6.0

0.59*

20.0 vs 9.0*

KEYNOTE-0103

Pembrolizumab vs doce PD-L1 PS ≥50% (n=442) Squamous (n=222)

2 mg: 5.0 vs 4.1 10 mg: 5.2 vs 4.1 NR for squamous

2 mg: 0.59* 10 mg: 0.59*

0.86

14.9 vs 8.2 17.3 vs 8.2

NR for squamous

0.54* 0.50* 0.74

30.0 vs 8.0* 29.0 vs 8.0*

NR for squamous

LUX-Lung 84 Afatinib vs erlotinib (n=795) All squamous

2.6 vs 1.9

0.81*

7.9 vs 6.8

0.81*

6.0 vs 2.8*

OAK5 Atezolizumab vs doce (n=850) Squamous (n=222)

2.8 vs 4.0 NR for squamous

0.95 NR for squamous

13.8 vs 9.6 8.9 vs 7.7

0.73* 0.73*

14 vs 13 NR for squamous

All agents listed are FDA and EMEA approved for the treatment of SqCC of the lung.

*P<0.05.

doce = docetaxel; EMEA = European Medicines Agency; FDA = US Food and Drug Administration; HR = hazard ratio; mo = months; NR = not reported; ORR = objective

response rate; OS = overall survival; PD-L1 = programmed death-ligand 1; PFS = progression-free survival; PS = proportion score; SqCC = squamous cell carcinoma.

52

ESMO Guidelines: Second-line Recommendations

Nivolumab (I, A; MCBS 5)

Pembrolizumab if PD-L1>1%

(I, A; MCBS 3 if PD-L1 >1%; MSBC 5 if PD-L1 >50%

Docetaxel (I, B)

Ramucirumab – docetaxel (I, B; MCBS 2)

Erlotinib (II, C)

Afatinib (I, C; MCBS 1)

;

MCBS = Magnitude of Clinical Benef it Scale; PD-L = programmed death-ligand.

1. Novello S et al. Ann Oncol. 2016;27(suppl 5):v1–v27.

53

SqCC of the Lung: Genetically Complex Malignancy • High burden of somatic mutations/genomic alterations1

• Overexpression/derangements of EGFR,2,3 HER2,4,5 HER4,6 and/or dysregulation of their downstream pathways

implicated in the pathogenesis of SqCC of the lung

1. Law rence et al. Nature. 2013;499:214; 2. López-Malpartida et al. Lung Cancer. 2009;65:23; 3. Hirsch et al. J Clin Oncol. 2003;21:3796; 4. Heinmoller et al. Clin Cancer Res.

2003;9:5238; 5. Ugocsai et al. Anticancer Res. 2005;25:306; 6. Cancer Genome Atlas Research Netw ork. Nature. 2012;489:519.

Pilo

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denocarc

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54

ErbB Pathway is Frequently Dysregulated in SqCC

of the Lung

1. Hirsch FR et al. J Clin Oncol. 2003;21:3798–807; 2. Lopez-Malpartida AV et al. Lung Cancer. 2009;65:25–33; 3. Lee HJ et al. Lung Cancer. 2010;68:375–82; 4. Gately K et al. Clin Lung Cancer. 2014;15:58–66; 5. Dacic S et al. Am J Clin Pathol. 2006;125:860–5; 6. Ji H et al. Proc Natl Acad Sci U S A. 2006;103:7817–22; 7. Dearden S et al. Ann Oncol. 2013;24:2371–6; 8. Jaiswal BS et al. Cancer Cell. 2013;23:603–17; 9. Gorgoulis V et al. Pathol Res Pract.

1995;191:973–81; 10. Kan Z et al. Nature. 2010;466:869–73; 11. Shepherd FA et al. N Engl J Med. 2005;352:123–32; 12. Clark GM et al. Clin Lung Cancer. 2006;7:389–94; 13. Leon et al. ESMO 2008. Abstract 1277 (poster);

14. Pirker R et al. Lancet. 2009;373:1525–31; 15. Pirker R et al. Lancet Oncol. 2012;13:33–42; 16. Thatcher N et al. ASCO 2014. Abstract 8008; 17. Li T et al. J Clin Oncol. 2013;31:1039–49.

Amp = amplif ication; EGFR = epidermal grow th factor receptor; FGFR = fibroblast grow th factor receptor; SqCC = squamous cell carcinoma.

ErbB Receptor Frequency

(%)

EGFR overexpression2–5 26–86

EGFR amplification2,5 15–27

EGFRvIII mutation6 5

EGFR kinase domain mutation7 <5%

ERBB2 mutation/amplification2 5

ERBB3 mutation8 1

ERBB3 overexpression9 10

ERBB410 8

Frequency of known genetic drivers in SqCC17

– EGFR overexpression, gene

amplification and aberrations of other

ErbB receptors have all been implicated

in the pathobiology of SqCC1,2

– These findings likely account for the

benefits these patients derive from

erlotinib11–13 and other EGFR-directed

therapies in different treatment

settings,14–16 despite the low frequency

of EGFR-activating mutations17

EGFRvIII

PI3KCA

EGFR

DDR2

FGFR1 Amp

Unknow n

~5%

55

Afatinib is the First Irreversible ErbB Family Blocker

1. Li et al. Oncogene. 2008;27:4702; 2. Solca et al. J Pharmacol Exp Ther. 2012;343:342.

• Afatinib covalently binds and

irreversibly blocks EGFR, HER2,

and ErbB4

• Targeting the whole ErbB Family enhances the effect on important

signaling pathways

56

LUX-Lung 8: Study Design

1. Soria JC et al. Lancet Oncol. 2015;16:897–907.

• Advanced SqCC NSCLC (Stage IIIB/IV)

• PD after ≥4 cycles of a first-line

platinum doublet

• ECOG PS 0 or 1

• No prior anti-EGFR therapy

• No active brain metastases

Afatinib (n=398)

40 mg qd

Erlotinib (n=397)

150 mg qd

Treatment

until disease

progression

or

unacceptable

AEs

Randomisation

1:1

(N=795)

• Stratification: East Asian vs non-East Asian

• Tumour tissue collected for correlative science

• Radiographic tumour assessment at baseline; Weeks 8, 12, 16; every 8 weeks

thereafter

• Primary endpoint: PFS; key secondary endpoint: OS

AE = adverse event; EGFR = epidermal grow th factor receptor; ECOG PS = Eastern Cooperative Oncology Group performance status; NSCLC = non-small cell lung cancer;

OS = overall survival; PD = disease progression; PFS = progression-free survival; qd = once daily; SqCC = squamous cell carcinoma.

57

1.0

LUX-Lung 8: Significant Improvement in PFS and OS

With Afatinib Compared With Erlotinib

1. Soria JC et al. Lancet Oncol. 2015;16:897–907.

397 99 34 17 10 2 0 1 1 1 Erlotinib

398 139 50 30 14 10 5 2 2 0

397 99 34 17 10 2 1 1 1 0

398 316 249 170 124 82 47 28 10 4 0

397 305 210 150 94 54 30 11 4 2 0

Afatinib

40 mg QD

(n=398)

Erlotinib

150 mg QD

(n=397)

Patients progressed or died, n (%) 299 (75.1) 306 (77.1)

Median PFS (months) 2.6 1.9

HR 0.81; 95% CI: 0.69–0.96;

P=0.0103

Afatinib

40 mg QD

(n=398)

Erlotinib

150 mg QD

(n=397)

Patients died, n (%) 307 (77.1) 325 (81.9)

Median OS (months) 7.9 6.8

HR 0.81; 95% CI: 0.69–0.95;

P=0.0077

Primary analysis of OS (key secondary endpoint) (n=795)

Pro

ba

bil

ity o

f P

FS

Updated PFS analysis by Independent Review (n=795)

3 6 9 12 15 18 21 24

0.2

0.4

0.6

0.8

0 0 27 3 6 9 12 15 30 18 21 24 27

0.2

0.4

0.6

0.8

1.0

0 0

36.4%

28.2% 22.0%

14.4%

Time (months) Time (months)

Pro

ba

bil

ity o

f O

S

Afatinib

Erlotinib

Afatinib

Erlotinib

No. at risk No. at risk

CI = confidence interval; HR = hazard ratio; OS = overall survival; PFS = progression-free survival; QD = once daily.

58

Post-hoc Analysis of LUX-Lung 8 Patients Deriving

Long-term Benefit1

1. Yang J et al. ELCC 2017. Poster #102P.

Post-hoc analysis identified 21 patients who received ≥12 months of afatinib

treatment

– Median treatment duration was 17.6 months (range: 12.3–27.6 months)

59

Post-hoc Analysis of LUX-Lung 8 Patients Deriving

Long-term Benefit1

1. Yang J et al. ELCC 2017. Poster #102P.

OS: Primary Analysis

(ITT population)

1.0

0.8

0.6

0.4

0.2

0

0 3 6 9 12 15 18 21 24 27 30

Time (months)

Es

tim

ate

d O

S p

rob

ab

ilit

y

36.4%

22.0%

28.2%

14.4%

Afatinib (n=398)

Erlotinib (n=397) • Median OS was 21.1 months

(range: 12.9–31.6 months)

• Median PFS was 16.6 months

(range: 2.8–25.8 months)

Afatinib OS, 7.9 mo

OS and PFS in Patients

Deriving Long-term Benefit

60

Treatment Response* and OS in Patients Deriving

Long-term Benefit

Yang J et al. ELCC 2017. Poster #102P.

*Stable disease unless noted otherw ise (patient 2 w as classified as non-evaluable); †Patients w ere ordered and numbered by treatment duration, w ith patient 1 being on

treatment longest; ‡First observed response at time of tumour measurement; §Last observed response at time of tumour measurement; ¶Treatment ongoing until death;

‖Received ≥1 line of chemotherapy after afatinib; CR = complete response; PR = partial response.

• Median OS was 21.1 months (range: 12.9–31.6 months)

• Median PFS (independent central review) was 16.6 months (range: 2.8–25.8 months)

61

Genomic Aberrations in Patients Deriving Long-term

Benefit

• ErbB family mutations were more frequent in LTRs than in the overall afatinib-treated

population

Yang J et al. ELCC 2017. Poster #102P.

*Next-generation sequencing w as undertaken in 10/21 LTRs and 132/398 afatinib-treated patients overall; WT = w ild-type.

LTRs (n=10*)

ErbB3, 0% ErbB4,

10.0%

ErbB WT, 50.0%

ErbB2, 20.0%

EGFR, 20.0%

All afatinib-treated patients (n=132*)

ErbB4, 2.3%

ErbB WT, 81.1%

ErbB2, 6.8%

EGFR, 6.8%

ErbB3, 4.6%

62

Experience With Afatinib for SqCC of the Lung:

Case Report From LUX-Lung 8

Baseline characteristics

• 59-year-old white male

• ECOG PS: 1

• Stage IV

• Primary site: left upper lobe

• Number of metastases: 2; no brain metastases

• Smoking status: ex smoker (41 pack-years)

Treatments

• First-line: carboplatin/paclitaxel (Aug 2012 to Oct 2012; best response: CR); no maintenance therapy

• Second-line: afatinib within LUX-Lung 8

Case study.

BMI = body mass index; COPD = chronic obstructive pulmonary disease; CR = complete response; DC = discontinued; ECOG PS = Eas tern Cooperative Oncology Group

performance status; OS = overall survival; PD = disease progression; PFS = progression-free survival; SqCC = squamous cell carcinoma.

63

Experience With Afatinib for SqCC of the Lung:

Case Report From LUX-Lung 8

Outcomes with second-line afatinib

• Treatment duration: 19.6 months (Mar 2013 to Nov 2014)

– Afatinib dosage: 40 mg for 28 days; 50 mg for 18.7 months

• PFS: 17.1 months • OS: 23.1 months

Biomarker analysis

• Mutation: HER2 E395K

Case study.

BM = bone metastasis; BMI = body mass index; COPD = chronic obstructive pulmonary disease; CR = complete response; DC = discontinued; ECOG PS = Eastern

Cooperative Oncology Group performance status; OS = overall survival; PD = disease progression; PFS = progression-free survival; SqCC = squamous cell carcinoma.

64

See You at the Poster!

• P3.01 – Advanced NSCLC (ID 621)

09:30 am – 04:00 pm | 10/18/2017 | Location: Exhibit Hall (Hall B + C)

Type: Poster Session with Presenters Present | Track: Advanced NSCLC

– P3.01-043 – Impact of ErbB Mutations on Clinical Outcomes in Afatinib- or

Erlotinib-Treated Patients with SCC of the Lung

Presenting Author: Glenwood Goss | Authors(s): Enriqueta Felip, M. Coco, Shun Lu, K. Syrigos, K.H. Lee, E. Göker, V. Georgoulias, W. Li, S. Guclu, D. Isla, Y. Joo Min, A. Morabito, A. Ardizzoni, Shirish M. Gadgeel, N. Gibson, N. Krämer, F. Solca,

A. Cseh, E. Ehmrooth, J. Soria

65

Summary and Conclusions

• LUX-Lung 81

Afatinib significantly improved PFS vs erlotinib: 2.6 vs 1.9 months

(HR 0.81; P=0.0427)

Afatinib significantly improved OS vs erlotinib: 7.9 vs 6.8 months

(HR 0.81, P=0.0077)

– Survival rates at 12 and 18 months favored afatinib

12 months (afatinib vs erlotinib): 36% vs 28% (P=0.016)

18 months: 22% vs 14% (P=0.013)

– In patients on afatinib for ≥ 12 months, a median survival benefit of nearly 2 years

was seen

ErbB family mutations were more frequent in this group3

1. Soria JC et al. Lancet Oncol. 2015;16:897–907; 2. Goss G et al. WCLC 2016; Presentation OA23.03; 3. Yang J et al. ELCC 2017. Poster #102P.

HR = hazard ratio; OS = overall survival; PFS = progression-free survival; SqCC = squamous cell carcinoma.

66

Summary and Conclusions

In treatment of SqCC, afatinib should be considered:

As a treatment option in patients who have failed previous

treatment with chemotherapy and immunotherapy

In the second-line setting in patients who are not eligible for

immune checkpoint inhibitors

1. Soria JC et al. Lancet Oncol. 2015;16:897–907; 2. Goss G et al. WCLC 2016; Presentation OA23.03; 3. Yang J et al. ELCC 2017. Poster #102P.

HR = hazard ratio; OS = overall survival; PFS = progression-free survival; SqCC = squamous cell carcinoma.

Panel Discussion Carrying the Data into the Clinic:

TKI Sequencing Decisions for EGFR Mutation-Positive NSCLC Patients


All Faculty

Moderator: T. Mitsudomi

BI Symposium

69

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of our staff as you exit the room.

70

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