ESMO SUMMIT LATIN AMERICA 2019 · 0 63 9 12 18 27 3315 21 3024 NIVO 368 291 258 230 22320 272 240...

ESMO SUMMIT LATIN AMERICA 2019

Immuno-oncology in Melanoma

Paolo A. Ascierto, MD Unit Melanoma, Cancer Immunotherapy and Innovative Therapies

Istituto Nazionale Tumori IRCCS Fondazione “G. Pascale”, Napoli, Italy

CONFLICT OF INTEREST DISCLOSURE

Paolo A. Ascierto

Consultant/advisory role:

Bristol-Meyers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre-Fabre,

Incyte, NewLink Genetics, Genmab, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs,

Sandoz, Immunocore.

Research funding:

Bristol-Meyers Squibb, Roche-Genentech, Array

Travel support:

MSD

Non-financial interests:

President of Fondazione Melanoma Onlus, Napoli, Italy. President of Campania Society of ImmunoTherapy of

Cancer (SCITO), Italy. Member of Steering Committee of Society of Melanoma Research (SMR). Member the Board

of Cancer Development Drug Forum (CDDF). Member of Board of Directors for the Society of Immuno-Therapy of

Cancer (SITC).

What we learned from Immuno-therapy in melanoma

Potential to improve clinical

outcomeIn various solid

and haematologicmalignancies

Targeting the immune system not the tumour offers the potential for activity across multiple

tumour types

Immune adaptability, and memory offers the

potential for long-term survival

Unique safety profiles

Efficacy as adjuvantDosage may makes a

difference

Unique MoAs offer the opportunity for

combination

Efficacy in brain mtx






tumour types





difference


combination

Same efficacy in brain mtx

Long-term benefit …

Keynote 006: Overall SurvivalMedian Follow-Up 45.9 (0.3-50.0) Months

aBased on Cox regression model with treatment as covariate stratified by line of therapy (1st vs 2nd), PD-L1 status (positive vs negative), and ECOG (0 vs 1); if no patients are in one of the treatment groups

involved in a comparison for a particular stratum, then that stratum was excluded from treatment comparison. bDerived by the product-limit (Kaplan-Meier) method for censored data. Data cutoff: Dec 4, 2017.

Events, n HRa (95% CI) Median,b mo (95% CI)

Pembro 309 0.73 (0.61-0.89) 32.7 (24.5-41.6)

Ipi 164 - 15.9 (13.3-22.0)

Events, n HRa (95% CI) Median,b mo (95% CI)

Pembro 193 0.73 (0.57-0.93) 38.7 (27.3-NR)

Ipi 104 - 17.1 (13.8-26.2)

All Patients

278 202 158 127 111 102 94 90 85 76 0 0 0

556 481 416 357 317 289 266 250 239 181 0 0 0

No. at risk

Overa

ll S

urv

ival, %

Time, months

100

90

80

70

60

50

40

30

20

10

05 10 15 20 25 30 35 40 45 50 55 600

181 140 105 86 76 70 64 63 60 51 0 0 0

Treatment-Naive Patients

368 324 284 248 221 201 186 174 167 124 0 0 0

No. at risk Time, months

100

90

80

70

60

50

40

30

20

10

0

5 10 15 20 25 30 35 40 45 50 55 600

Overa

ll S

urv

ival, %

34.1% 41.7%

37.8%48.1%

42.4%55.2%

44.7% 58.0% 51.2%

40.8% 36.4% 44.3%

Long et al ASCO 2018

Keynote 001: Overall Survivala

aDerived by the product limit (Kaplan-Meier) method of censored data. Data cutoff: Sep 1, 2017.Hamid et al ASCO 2018

NIVO+IPI (n = 314) NIVO (n = 316) IPI (n = 315)

Median OS, mo (95% CI)NR

(38.2, NR)36.9

(28.3, NR)19.9

(16.9, 24.6)

HR (95% CI) versus IPI0.54

(0.44, 0.67)0.65

(0.53, 0.79)–

HR (95% CI) versus NIVOa 0.84 (0.67, 1.05)

– –

Checkmate 067: Overall Survival

Months

0

10

20

30

40

50

60

70

80

90

100

0 3 6 9 12 15 18 573024 362721 45 5133 39 5442 48

Patients at risk:

0IPI 253285315 227 203 181 163 148 135 128 113 107 99 94 93 90 86 50 11

0265292314NIVO+IPI 247 226 221 209 200 198 192 186 180 178 171 166 160 154 96 13

NIVO 0266292316 245 231 214 201 191 181 175 171 164 158 150 144 140 135 85 18

64%58%

53%

59%

51%46%45%

34%30%

aDescriptive analysis

OS

(%

)

NIVO+IPI

NIVO

IPI

Hodi et al ESMO 2018






tumour types





difference


combination

Treatment decision based on patient's characteristic

Patient history

(eg, autoimmune disease)

Performance status

Tumor burden

Organ system function,

especially cardiac function

Patient’s wishes and

lifestyle factors

LDH level

Mutational status

Brain mtx

Disease Tempo

Ascierto ESMO 2016

Clinical risk factors and Immune status

LDH, lactate dehydrogenase Ascierto and Dummer. Oncoimmunology. 2018

De Mattos-Arruda et al. Nature Reviews Clinical Oncology 2016

Adjuvant setting: early selection of resistant clones

Pa

tie

nts

a

live

(%)

*Stratified by stage at randomization

Ipilimumab Placebo

Deaths/patients 162 / 475 214 / 476

Hazard ratio (95.1% CI)* 0.72 (0.58 - 0.88)

Log-rank P value* 0.001

EORTC 1807: Overall Survival

65%

54%

5-year

difference

11%

CI = confidence interval; NR = not reached.Eggermont et al. NEJM 2016

Years0 1 2 3 4 5 6 7 8

0

10

20

30

40

50

60

70

80

90

100

O N Number of patients at risk :

162 475 431 369 325 290 199 62 4

214 476 413 348 297 273 178 58 8

Ipilimumab

Placebo

CheckMate 238: 24-Month Follow-Up

Primary Endpoint: RFS in All Patients

RF

S (

%)

Months

0

10

20

30

40

50

60

70

80

90

100

0 6 12 18 24 273 9 15 21 30 33

NIVO

IPI

Number of patients at risk

NIVO

IPI

NIVO IPI

Events/patients 171/453 221/453

Median (95% CI) 30.8 (30.8, NR)a 24.1 (16.6, NR)

HR (95% CI) 0.66 (0.54, 0.81)

Log-rank P value <0.0001

63%

50%

70%

60%

453 353 311 280 205 28394 331 291 264 7 0

453 314 251 216 149 23363 270 230 204 5 0

66%

53%

aMedian estimate not reliable or stable due to few patients at risk.

Weber et al. ASCO 2018


PD-L1 <5% PD-L1 ≥5%NIVO IPI


Median (95% CI) NR (21.7, NR) 15.9 (10.3, 25.5)

HR (95% CI) 0.73 (0.57, 0.92)

NIVO IPI


Median (95% CI) 30.8 (30.8, NR)a 27.2 (22.4, NR)a

HR (95% CI) 0.54 (0.36, 0.81)

Subgroup Analysis of RFS: 5% PD-L1 Expression Level

NIVO

IPI

Months

0

10

20

30

40

50

60

70

80

90

100

0 6 12 18 27 333 9 15 21 3024

152 130 122 112 10 0135 125 115 106NIVO 287

154 120 104 88 4 0133 108 94 81IPI 161


82%

72%

76%

58%

NIVO

IPI

Months

0

10

20

30

40

50

60

70

80

90

100

0 6 12 18 27 333 9 15 21 3024

275 204 171 151 17 0238 188 158 141NIVO 5108

286 184 139 121 17 0218 154 128 116IPI 383


64%

53%

55%

46%

59%

48%

79%

63%


RF

S (

%)

RF

S (

%)



Stage III Stage IV

NIVO IPI


Median (95% CI) NR 25.5 (16.6, NR)

HR (95% CI) 0.68 (0.54, 0.85)

NIVO IPI


Median (95% CI) 30.8 (15.9, NR)a 15.4 (8.5, NR)

HR (95% CI) 0.68 (0.44, 1.06)

Subgroup Analysis of RFS: Disease Stage III and IV

NIVO

IPI

RF

S (

%)

Months

0

10

20

30

40

50

60

70

80

90

100

0 6 12 18 27 333 9 15 21 3024

368 291 258 230 22 0320 272 240 217NIVO 4166

366 259 207 179 18 0298 223 190 169IPI 3121


72%

61%

64%

52%

NIVO

IPI

RF

S (

%)

Months

0

10

20

30

40

50

60

70

80

90

100

0 6 12 18 27 333 9 15 21 3024

82 59 51 48 6 071 56 49 45NIVO 337

87 55 44 37 5 065 47 40 35IPI 228


63%

56%

58%

44%

67%

55%

61%

47%




Stage IIIB Stage IIIC

NIVO IPI


Median (95% CI) NR NR (24.2, NR)

HR (95% CI) 0.68 (0.47, 1.00)

NIVO IPI


Median (95% CI) NR (24.9, NR) 16.6 (9.4, 27.2)

HR (95% CI) 0.68 (0.52, 0.91)

NIVO

IPI

RF

S (

%)

Months

0

10

20

30

40

50

60

70

80

90

100

0 6 12 18 27 333 9 15 21 3024

165 132 120 112 13 0146 123 116 109NIVO 184

148 118 99 86 9 0133 107 89 82IPI 358


76%

70%

71%

61%

NIVO

IPI

RF

S (

%)

Months

0

10

20

30

40

50

60

70

80

90

100

0 6 12 18 27 333 9 15 21 3024

203 159 138 118 9 0174 149 124 108NIVO 382

218 141 108 93 9 0165 116 101 87IPI 063


69%

55%

58%

45%

74%

63%

62%

49%

Subgroup Analysis of RFS: Disease Stage IIIB and Stage IIIC



BRAF Mutant BRAF Wild typeNIVO IPI


Median (95% CI) 30.8 (30.8, NR)a 24.6 (14.8, NR)

HR (95% CI) 0.73 (0.54, 0.99)

NIVO IPI


Median (95% CI) NR 16.6 (11.4, NR)

HR (95% CI) 0.61 (0.45, 0.82)

NIVO

IPI

RF

S (

%)

Months

0

10

20

30

40

50

60

70

80

90

100

0 6 12 18 27 333 9 15 21 3024

187 142 126 117 16 0157 135 120 110NIVO 483

194 142 112 96 11 0155 118 103 91IPI 267


68%

62%

62%

52%

NIVO

IPI

RF

S (

%)

Months

0

10

20

30

40

50

60

70

80

90

100

0 6 12 18 27 333 9 15 21 3024

197 154 137 121 11 0172 144 127 115NIVO 291

212 138 109 91 9 0171 121 97 85IPI 362


72%

56%

64%

46%

65%

54%

66%

49%


Subgroup Analysis of RFS: BRAF Mutation Status







tumour types





difference


combination


Ipilimumab + nivolumab in Brain Metastases

Tawbi et al. ASCO 2017

Tawbi et al. NEJM 2018

CheckMate 204 is a multicenter study conducted across 28 sites and is the first phase 2 study investigating the safety and efficacy of NIVO+IPI in

patients with MEL that has metastasized to the brain

Intracranial ORR: 56%

Intracranial DCR: 57 %

Patient Case

71 year old male with BRAF V600E-mutated MEL, ~7 brain mets, no steroids or SRT

Baseline

1 year

Tawbi et al ASCO 2017

Ipilimumab + nivolumab in Brain Metastases

Long et al. ASCO 2017

Ascierto and Mc Arthur JTM 2017

Progression free survival curves from the most recent studies on advanced

melanoma patients with brain metastases






tumour types





difference


combination


OS for BRAF-mutation positive (n=173) and BRAF wild-type (n=296) patients

BRAF-mutation positive

BRAF wild-type

Median OS, months

1-year OS, %

2-year OS, %

Time (months)

BRAF-mutation

positive (n=173)

BRAF

wild-type (n=296)

8.5

39

18

11.6

48

24

0 6 12 24 18 30 36

100

60

40

80

20

0

OS

(%

)

P= NS

Ascierto et al. J Trans Med 2011

47%

CA184-169 study: OS by BRAF Mutation

Ascierto et al. Bridge meeting, Naples 1 Dec 2018

CA184-169

BRAF Wild-type BRAF Mutant

Patients at risk:

IPI 10 mg/kg

IPI 3 mg/kg

Months

OS

(%

)

0

10

20

30

40

50

60

70

80

90

100

0 3 6 9 12 15 18 573024 362721 45 5133 39 5442 48 60 63 66

Patients at risk:

IPI 10 mg/kg

IPI 3 mg/kg

Months

OS

(%

)

0

10

20

30

40

50

60

70

80

90

100

0 3 6 9 12 15 18 573024 362721 45 5133 39 5442 48 60 63 66

80 72 63 58 55 53 49 274044 354146 31 3039 34 2934 30 25 5 0

79 73 62 54 46 42 39 182533 202836 18 1823 19 1818 18 17 2 0

225 19015713311910792 476374 616886 53 5063 57 4853 50 42 6 0

237203166136110 93 83 415767 556275 48 4555 52 4451 46 37 5 0

IPI 10 mg/kg

IPI 3 mg/kg

53%

34%

30%

28%

25%

24%

21%

22%

19%

70%

59%

57%

42%

45%

26%

39%

23%

35%

NA

IPI 10 mg/kg IPI 3 mg/kg


Median (95% CI), months

13.8 (10.2−17.0) 11.2 (9.2−13.8)

IPI 10 mg/kg IPI 3 mg/kg


Median (95% CI), months

33.2 (19.4−45.2) 19.7 (11.6−25.3)

IPI 10 mg/kg

IPI 3 mg/kg

Minimum OS follow-up ~61 months Minimum OS follow-up ~61 months

OS in Patients With BRAF Wild-type and Mutant Tumors

BRAF Wild-type BRAF Mutant

NIVO+IPI NIVO IPI

Median, mo

(95% CI)

39.1

(27.5, NR)

34.4

(24.1, NR)

18.5

(14.1, 22.7)

HR (95% CI)

versus IPI

0.60

(0.47, 0.77)

0.65

(0.51, 0.83)–

HR (95% CI)

versus NIVOa

0.92

(0.71, 1.20)– –

NIVO+IPI NIVO IPI

Median, mo

(95% CI)NR

45.5

(26.4, NR)

24.6

(17.9, 31.0)

HR (95% CI)

versus IPI

0.45

(0.30, 0.67)

0.64

(0.44, 0.93)–

HR (95% CI)

versus NIVOa

0.70

(0.46, 1.07)– –

MonthsPatients at risk:

IPI

NIVO+IPI

NIVO

0165194215

0169193211

0180199218

146

156

164

132

143

156

117

141

145

105

132

134

95

126

127

86

125

124

81

119

119

72

115

116

70

109

111

64

108

106

62

102

102

61

99

98

58

98

96

57

94

93

33

54

56

9

6

12

53%

49%

32%

49%

45%

28%

NIVO+IPI

NIVO

IPI

68%

56%

37%

62%

50%

33%

MonthsPatients at risk:

IPI

NIVO+IPI

NIVO

08891100

09699103

0869398

81

91

81

71

83

75

64

80

69

58

77

67

53

74

64

49

73

57

47

73

56

41

71

55

37

71

53

35

70

52

32

69

48

32

67

46

32

62

44

29

60

42

17

42

29

2

7

6

NIVO+IPI

NIVO

IPI

OS

(%

)

0

20

40

60

80

100

0 3 6 9 12 15 18 573024 362721 45 5133 39 5442 48

OS

(%

)

0

20

40

60

80

100

0 3 6 9 12 15 18 573024 362721 45 5133 39 5442 48

aDescriptive analysis Hodi et al. ESMO 2018

Hypothetical model about how BRAFV600 mutation in melanoma cells could affect the tumor microenvironment

and response to ipilimumab and combination of ipilimumab and nivolumab.

Ascierto PA & McArthur JA. J Transl Med 2017;15:173






tumour types





difference


combination


Tissues of the body affected by

autoimmune attack

The clinical spectrum of IRAEs

(immune-related adverse events)

Festino and Ascierto. Oncoimmunology Eds 2017

Most frequent irAEs

Grade 3-4 AEs

%

% of Pts who

permantely

discontinued

for any grade

Ipilimumab 3 mg/kg1 27 15.4

Ipilimumab 10 mg/kg1 34 31

Nivolumab2 13 6

Pembrolizumab 2 mg/kg3 13.5 4.5

Ipilimumab/Nivolumab4 56.5 38.7

1. Ascierto et al. ESMO 2016

2. Atkinson et al. SMR 2015

3. Hamid ESMO 2016

4. Wolchock et al ASCO 2016

Distribution of grade I–II and grade III–V IRAEs for all tumour types in the main clinical trials with anti-

CTLA4, anti-PD-1 or anti-PD-L1 antibodies as single therapy

Michot JM et al. Eur J Cancer 2016

Immune-

mediated

adverse

reactions

Treatment algorithms/experience aid early diagnosis and management of immune-mediated adverse reactions

Patient education for

early recognition

Early diagnosis

and appropriate

management essential

to minimise

life-threatening

complications

Systemic high-dose

corticosteroids*

may be required for

severe events

Can be severe or

life-threatening; may

involve various organs

Result from increased

or excessive immune

activity

Unless an alternate

aetiology has been

identified, consider all

signs and symptoms

*With or without additional immunosuppressive therapy






tumour types





difference


combination


Long-term benefit …

30%

How can we make more responsive the tumor?

(overcoming primary resistance)

How can we reduce the risk of relapse?

(overcoming acquired resistance)

2

Chen DS, Mellman I Nature 2017; 541, 321–330.

Cancer-immune phenotypes

Potential combination strategies for the treatment of cancer

Immunotherapy plus

immunotherapy

Immunotherapy plus

chemotherapy

Immunotherapy plus

targeted therapy

Immunotherapy plus

radiotherapy

Potential

combinations


Immunotherapy plus

immunotherapy

Potential

combinations

Ascierto PA & McArthur JA. J Transl Med 2017;15:173

New emerging pathways for future combination with anti-PD-1/PD-L1 compounds

IDO1 inhibitor

(eg., epacadostat [Ph 3], etc.)

Anti-LAG-3

(eg., relatlimab [Ph 1/2])

HDAC inhibitor

(eg., entinostat [Ph 2])

Anti-GITR

(eg., BMS-986156 (Ph 1/2])

GITR, glucocorticoid-induced TNFR-related protein; HDAC, histone deacetylases;

IDO1, indoleamine 2,3-dioxygenase 1; LAG-3, lymphocyte-activation gene 3 Presented by Paolo A. Ascierto at ASCO 2018

Immunotherapy plus

targeted therapy

Potential

combinations


BRAF/MEK inhibitors as immunomodulating agents

ADE, adensosine; IFNAR, interferon-α/β receptor; MHC, major histocompatibility complex;

TAA, tumour-associated antigen; Treg, regulatory T cell Image modified from Ascierto & Dummer, Oncoimmunology 2018

Tumour microenvironment

before BRAFi and MEKi

Tumour microenvironment after

BRAFi and MEKi:

↓ Adenosine ↓ Treg and myeloid-derived suppressor cells

↑ Activity of CD4-CD8+ lymphocytes

BRAFi/MEKi induce profound changes in:

Antigen display ↑Expression of MHC ↑ IFNAR ↑ and CD73 ↓

Melanoma cell

MEK

ERK

NRAS

BRAF

MEKi

BRAFi

MHC ↑

IFNAR ↑

TAA ↑

CD73 ↓

T reg

CD4-CD8+ lymphocytes

Myeloid-derived suppressor cells

Paolo A. Ascierto

Targeted therapy with immunotherapy – a rational combination for advanced BRAFV600 mutant melanoma

Figure modified from Ribas et al., Clin Cancer Res. 2012.

Immunotherapy

Pe

rce

nt a

live

Years1 2 30

Combination

Pe

rce

nt a

live

Years1 2 30

Targeted therapy

Pe

rce

nt a

live

Years1 2 30

+ =

Rapid and clinically

significant

tumour response

Less frequent tumour

response, but clinically

significant durability

Durable tumour response

and prolonged survival?

BID, twice daily; CR, complete response; PD, progressive disease; PR, partial response; QD, once daily; SD, stable disease. a Patients with CR and < 100% change in sum of diameters (SOD) have (a) 100% change for non-nodal target

lesions and all nodal target lesions are < 10 mm and (b) CR for nontarget lesions. b Patients with PR and 100% change in SOD have (a) 100% change for all target lesions and (b) non-CR/non-PD response for nontarget lesions.

1. Ribas A, et al. J Clin Oncol. 2015; 33(suppl) [abstract 3003]; 2. Ribas A, et al. J Clin Oncol. 2016; 34(suppl) [abstract 3014]; 3. Ribas A, et al. Ann Oncol. 2017; 28(suppl 5)

[abstract 1216O]; 4. Hwu P, et al. Ann Oncol. 2016; 27(suppl 6) [abstract 1109PD]; 5. Dummer, R, et al. J Clin Oncol. 2018;36(suppl 5S) [abstract 189].

Clinical Trials Combining BRAFi + MEKi+ anti–PD-1/L1

PRESENTED BY R DUMMER AT AACR 2018

Courtesy of Dr Dummer

Dabrafenib + trametinib

+ pembrolizumab2,3

Vemurafenib + cobimetinib

+ atezolizumab4


+ durvalumab1


+ spartalizumab5

100

80

60

40

20

0

−20

−40

−60

−80

−100

Ch

an

ge f

rom

baseli

ne,

% Complete responsea

Partial response

Study treatment ongoing

N = 9

*0 4 8 12 16 20 24

Time, months

4

V600E

V600K

*

* *

*

**

0 4 8 12 16 20 24

−100−80−60−40−20

0

20

40

60

80

100

Time, months

Ch

an

ge f

rom

baseli

ne,

%

*

0 8 16 24 32 40 48

−100

−50

0

50

Time, weeks

56 64

Ch

an

ge f

rom

Baseli

ne,

%

55453525155

−5−15−25−35−45−55−65−75−85−95

V600E

V600K

Treatment ongoing

PR

CR

PD

Unconfirmed

response

100

80

60

40

20

0

−20

−40

−60

−80

−100

Best

ch

an

ge f

rom

baseli

ne

(measu

rab

le l

esio

ns),

% Complete responsea

Partial responseb

N = 9

0 20 24 100 252 260 410

Time, days

240 6 12 18 30 36 42 48 54 60 66 72 78

Time, weeks

Time to and on-treatment responseTime to responseD/C treatment

Response ongoing

0

40

20

−20

−40

−60

−80

−100

Best

ch

an

ge i

n S

LD

fro

m b

aseli

ne,

%

M1A

M1A

M1C

M1C

IV IVM1B

M1C

M1C

M1B

Un

kn

ow

n

Un

kn

ow

n

M1A

IV IV IV M1C

M1B

M1A

IVIVIIIC

IIIC

IIIC

IIIC

IIIC

IIIC

IIIC

IIIC

PD

SD

CR-PR

Discontinued all treatment

New lesion

0 2 3 4 5 6 7

Months From First Dose of Study Drug

8 9 101

Ch

an

ge f

rom

baseli

ne,

%

0 2 4 6 8 10 12

Time, months

No. at risk

14 16 18 20 22 24 26

Pembro + D + T 60 55 49 39 36 34 27 21 17 12 5 4 1 0

Placebo + D + T 60 59 52 38 35 29 23 20 16 9 4 3 0 0

100

90

80

70

60

50

40

30

20

10

0

PF

S %

Events, n

Median,a mo (95% CI)

HRb

(95% CI)bP Valuec

Pembro + D + T 31 16.0 (8.6-21.5)0.66 (0.40-1.07) 0.04287

Placebo + D + T 41 10.3 (7.0-15.6)

Progression-Free Survival

aBased on Kaplan-Meier estimate of PFS, per investigator assessment.bBased on Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs 1) and LDH (LDH >1.1 × ULN vs =1.1 × ULN); owing to the small number of patients enrolled in the ECOG PS 1 and LDH ≤1.1 × ULN strata, these strata were combined.cOne-sided P value based on stratified log-rank test.Data cutoff: Feb 15, 2018.

59%

45%

PFS did not reach

statistical significance

threshold per study

design (required HR

for significance ≤0.62, P ≤ 0.025)

PRESENTED BY PA Ascierto at ESMO 2018

Pembro + D + T 60 60 59 56 53 50 43 35 29 23 18 9 4 1

Placebo + D + T 60 60 59 55 51 47 39 36 31 25 18 7 2 0

0

0

No. at risk

0 2 4 6 8 10 12

Month

14 16 18 20 22 24 26

100

90

80

70

60

50

40

30

20

10

0

Ove

rall

Su

rviv

al,

%

28

Overall Survival

aBased on Kaplan-Meier estimate of overall survival.bBased on Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs 1) and LDH (>1.1 × ULN vs ≤1.1 × ULN; owing to the small number of patients enrolled in the ECOG PS 1 and LDH ≤1.1 × ULN strata, these strata were combined. cP values are provided for descriptive purposes only, no multiplicity adjustment is made. One-sided P value based on stratified log-rank test.Data cutoff: Feb 15, 2018.

Events, n

Mediana

(95% CI), moHRb

(95% CI)bP Valuec

Pembro + D + T 19 NR (19.6-NR)0.76 (0.41-1.39) 0.18467

Placebo + D + T 24 23.4 (17.8-NR)

79%

73%

PRESENTED BY PA Ascierto at ESMO 2018

TAKE HOME MESSAGES

With the new treatments (mainly with I-O) about the half of metastatic

melanoma patients can reach a long-term benefit

I-O may be used in earlier stages (Stage III) of the disease as

adjuvant post-surgery

New combination studies are ongoing in order to find more efficacy

treatments with less side effects.

Cancer immunotherapy-based combination studies underway in 2016

Tang J, et al. Annals of Oncology 2017;29:84–91DRG. Landscape & forecast. Immune checkpoint inhibitors special topic

report. Dec 2017

Agents used in combination with PD-1- or PD-L1-targeting agents. The size of the bubble represents the number of trials.

Thank you!

Via Mariano Semmola, 80131, Napoli, Italy

Tel. +39 081 5903 431; Fax +39 081 5903 841

Email: [email protected]

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Transcript of ESMO SUMMIT LATIN AMERICA 2019 · 0 63 9 12 18 27 3315 21 3024 NIVO 368 291 258 230 22320 272 240...