AVN - Presentatie - Sjaak Burgers

Mesothelioom 2021

Sjaak Burgers 30 November 2021

TITEL VAN DE PRESENTATIE

Het grote nieuws van de afgelopen jaar • Immuuntherapie2 lijkt (toch) ook te werken bij een deel van de mesothelioompatienten

KLIK OP ICOON OM AFBEELDING IN TE VOEGEN

De studie. Checkmate 743

Wie mag er meedoen?

• Geen eerdere behandeling • Goede conditie

Epithelioide en niet-epitheloide type en Mannen en vrouwen eerlijk over beide groepen verdeeld

Primary endpoint • OS

n = 303 N = 605

R 1:1 n = 302

NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W (max 2 jaar)

Tot groei v.d. tumor, of te veel bijwerkingen

Cisplatin of carboplatin + pemetrexed Q3W (6 kuren) b

Secondary endpoints • ORR, DCR, and PFS by BICR • Efficacy by PD-L1c expression

Database lock: May 7, 2021; minimum / median follow-up for OS: 35.5 months / 43.1 months.

Exploratory endpoints • Safety and tolerability • Biomarkers

NCT02899299; bCisplatin (75 mg/m2) or carboplatin (AUC 5) + pemetrexed (500 mg/m2), Q3W for 6 cycles; cDetermined by the PD-L1 IHC 28-8 pharmDx assay (Dako).

a

3

Update na 3 jaar: de overleving 100

OS (%)

80

Median OS,a mo HR (95% CI)

68%

60

58%

NIVO + IPI Chemo (n = 303) (n = 302) 18.1 14.1 0.73 (0.61–0.87)

41%

40

23%

27%

20

NIVO + IPI

15% 0

0

No. at risk NIVO + IPI 303 Chemo 302

Chemo

3

6

9

12

15

18

21

24 27 30 maanden

33

36

39

42

45

48

51

54

273 269

251 234

226 192

200 164

173 138

145 114

126 97

116 76

73 46

62 43

49 33

35 20

18 11

7 6

2 0

0 0

97 69

80 54

Minimum follow-up: 35.5 months.

Subsequent systemic therapy was received by 45% of patients in the NIVO + IPI arm and 42% in the chemo arm; subsequent immunotherapy was received by 4% and 22%; subsequent chemotherapy was received by 43% and 33%, respectively. a 95% CIs were 16.8–21.0 (NIVO + IPI) and 12.4–16.3 (chemo).

4

Bij wie werkt het het best? Overleving: Median OS, mo NIVO + IPI (n = 303)

Chemo (n = 302)

Unstratified HR

All randomized (N = 605)

18.1

14.1

0.75a

< 65 years (n = 167) ≥ 65 to < 75 years (n = 281) ≥ 75 years (n = 157)

17.2 20.3 16.9

13.3 14.5 15.5

0.78 0.67 0.91

Male (n = 467) Female (n = 138)

17.5 21.1

13.7 18.0

0.73 0.82

ECOG PS 0 (n = 242) ECOG PS ≥ 1b (n = 363)

20.7 17.0

19.5 11.6

0.90 0.66

Never smoker (n = 249) Former smokerc (n = 318)

17.9 17.6

14.1 14.9

0.74 0.79

Epithelioid (n = 455) Non-epithelioidd,e (n = 150)

18.2 18.1

16.7 8.8

0.85 0.48

PD-L1 < 1% (n = 135) PD-L1 ≥ 1%f (n = 451)

17.3 18.0

16.6 13.3

0.99 0.71

Subgroup

Unstratified HR (95% CI)

-0.5

0

0.5

NIVO + IPI

1

1.5

Chemo

Minimum follow-up: 35.5 months.

Bold text indicates study stratification factors. a Stratified HR, 0.73; bOne patient in the chemotherapy group had a baseline ECOG PS of 2 (protocol deviation); c26 patients were current smokers; smoking status of 12 patients was unknown; d Includes sarcomatoid, mixed, and other; eOne patient was changed from epithelioid to non-epithelioid after the primary analysis; fPD-L1 expression level was not reported for 19 patients.

2

5

Na 3 jaar: overleving naar type MM Epithelioid 100 Median OS,b mo HR (95% CI)

NIVO + IPI Chemo (n = 229) (n = 226) 18.2 16.7 0.85 (0.69–1.04)

100 Median OS,c mo

69%

Chemo (n = 76) 8.8

0.48 (0.34–0.69)

63%

66%

60

NIVO + IPI (n = 74) 18.1

HR (95% CI)

80 OS (%)

OS (%)

80

Non-epithelioid

60

IER KOMEN WE OP TERU 42%

40

24%

33%

20 0

NIVO + IPI

19% Chemo 0

6

12

18

No. at risk

24 30 36 Months

42

48

54

38%

40

33%

22%

20

NIVO + IPI

10% 0

0

6

12

18

NIVO + IPI 74

59

46

34

26

17

52

23

13

7

4

No. at risk

NIVO + IPI 229

192

154

111

90

63

48

29

4

0

Chemo 226

182

141

101

69

50

40

18

5

0

4%

Chemo

76

24 30 36 Months

Chemo 42

48

54

14

6

3

0

3

2

1

0

Minimum follow-up: 35.5 months.

In patients with epithelioid histology, subsequent systemic therapy was received by 47% in the NIVO + IPI arm vs 44% in the chemo arm; subsequent immunotherapy was received by 4% vs 22%; subsequent chemotherapy was received by 45% vs 35%, respectively. In patients with non-epithelioid histology, subsequent systemic therapy was received by 39% in the NIVO + IPI arm vs 37% in the chemo arm; subsequent immunotherapy was received by 5% vs 20%; subsequent chemotherapy was received by 38% vs 26%, respectively. a Histology per CRF; b95% CIs were 16.9–21.9 (NIVO + IPI) and 14.9–20.3 (chemo); c95% CIs were 12.2–22.8 (NIVO + IPI) and 7.4–10.2 (chemo).

6

Als je nivo+ipi moet stoppen ivm bijwerkingen?

100

80%

OS (%)

80

NIVO + IPI All randomized Discontinued due to TRAEs

68%

60

Patients who discontinued all components of NIVO + IPI due to TRAEs NIVO +

IPI (n = 52)

Median OS,c mo

56%

3-year OS rate, % 40

37%

41%

20

ORR,d n (%) Median DOR after discontinuation,e mo

23%

0 0 No. at riskb 52 Discontinued

6 48

12 41

18 31

24 30 36 Months 27

20

17

42 12

48 3

54 0

25.4 37 35 (67) 20.0

Ongoing response for ≥ 3 years e 34 f all components of NIVO Among who discontinued + IPI due afterpatients discontinuation, % to TRAEs:

• Median (range) number of doses was 9 (1–47) for NIVO and 3 (1– 16) for IPI • Median (range) duration of treatment was 4.3 (0.0–22.5) months

Minimum follow-up for all randomized: 35.5 months.

Post hoc analysis and includes patients with TRAEs (reported between first dose and 30 days after last dose of study treatment) that were considered leading to discontinuation of all components of study treatment; bNo. at risk for all-randomized population at Month 0 was 303; c95% CI was 17.9–40.2; dAmong patients with an objective response, 3 (6%) had CR, 32 (62%) had PR, 11 (21%) had SD, 4 (8%) had PD, and 2 (4%) were not reported; e7 responders (among patients who discontinued due to TRAEs) in the NIVO + IPI arm had their responses ended before treatment end date and therefore were excluded from the analysis of duration of response after discontinuation; f95% CI was 14–56. a

7

MID

Deterioration

Worse

10 0 −10

MID Improvement

−20 −30 −40 2 6 12 18 24 30 36 42 48

No. at risk NIVO + IPI Chemo

206 189 174 151 131 108 199 178 86 12 21 208

94 9

80 3

60

72

84

96

54 2

42 1

32 0

23 0

Weeks

73 5

108 5 0

Worse

Chemo

Deterioration

Improvement

2 6 12 18 24 30 36 42 48 No. at risk NIVO + IPI Chemo

NIVO + IPI

Better

20

Epithelioidc

Weeks

60

72

84

96

108

158 148 136

116

103

83

73

60

57

44

32

25

18

0

151 145 136

71

10

21

8

3

5

2

1

0

0

0

40 30 20 MID 10 0 −10 MID −20 −30 −40

Non-epithelioidd

NIVO + IPI Chemo

Worse

30

40 30 20 MID 10 0 −10 MID −20 −30 −40

Deterioration

Better

NIVO + IPI Chemo

Mean (± SE) change from baseline

Overall

b,c

Better

Mean (± SE) change from baseline

40

Mean (± SE) change from baseline

Disease-related symptom burden: LCSS-Meso ASBI a mean change from baseline (on treatment)

Improvement

No. at risk NIVO + IPI

60

72

84

96

108

48 41

2 6 12 18 24 30 36 42 48 38

35

28

25

21

20

16

10

10

7

5

0

Chemo

57 54

42

15

2

0

1

0

0

0

0

0

0

0

Weeks

Completion rates out of expected patients were mostly above 80%. Only timepoints with data for ≥ 10 patients in either treatment group are shown. a LCSS-Meso ASBI is the average of 6 disease-related symptom scores on a 100-mm VAS; range: 0 (best) to 100 (worst); MID = 10 points; bIn the NIVO + IPI arm, there were 191 patients at week 4 and 167 patients at weeks 8 and 10; in the chemo arm, there were 180 patients at week 9; cFor the NIVO + IPI arm, mean (SD) at baseline was 30.7 (22.4) for 261 pts, 31.2 (24.0) at follow-up visit 1 for 128 pts, and 31.7 (21.0) at follow-up visit 2 for 103 pts. For the chemo arm, baseline mean (SD) was 30.3 (24.7) for 234 pts, 32.8 (25.9) at follow-up visit 1 for 143 pts, and 30.2 (22.6) at follow-up visit 2 for 115 pts. dIn the NIVO + IPI arm there were 200 patients at baseline, 148 patients at week 4, 130 patients at week 8, and 131 patients at week 10; in the chemo arm there were 171 patients at baseline and 132 patients at week 9; eIn the NIVO + IPI arm, there were 61 patients at baseline, 43 patients at week 4, 37 patients at week 8, and 36 patients at week 10; in the chemo arm there were 63 patients at baseline and 48 patients at week 9.

NIPIMES

First-line tre atment Nivolumab + IPIlimumab ve rsu s platinu m agent s + pemet rexed in pat ie nts with malignant pleural ME Sot helioma: a propensity score analysis base d on real-world dat a.

Li-Anne Douma 03 November 2021 European Thoracic Oncology Platform (ETOP)

ASCO 2021

10

AFGEROND, RESULTATEN NOG NIET BEKEND: de PEMMELA studie

Dianne de Gooijer – Li-Anne Douma – Paul Baas – Sjaak Burgers

Patienten • Wie kon er meedoen: • Het mesothelioom groeit na 1 of 2 eerdere series chemotherapie • De ziekte is meetbaar • Goede conditie • Goede lever en nieren • Goede bloeddruk • Geen recente TIA of hartaanval

Behandeling • Pembrolizumab: 3-wekelijks infuus • Lenvatinib: iedere dag tabletten

De immuuntherapie en de “vaatingroeiremmer” versterken in theorie elkaars werking

13

Doel van de studie: • De tumor wordt kleiner bij minimaal 12 van de 36 patienten.

• Hoe lang blijft de tumor dan onder controle?

• Snappen we waarom dit soms wel/soms niet lukt?

14

Na 3 jaar: overleving naar type MM Epithelioid 100 Median OS,b mo HR (95% CI)

NIVO + IPI Chemo (n = 229) (n = 226) 18.2 16.7 0.85 (0.69–1.04)

100 Median OS,c mo

69%

Chemo (n = 76) 8.8

0.48 (0.34–0.69)

63%

66%

60

NIVO + IPI (n = 74) 18.1

HR (95% CI)

80 OS (%)

OS (%)

80

Non-epithelioid

60

IER KOMEN WE OP TERU 42%

40

24%

33%

20 0

NIVO + IPI

19% Chemo 0

6

12

18

No. at risk

24 30 36 Months

42

48

54

38%

40

33%

22%

20

NIVO + IPI

10% 0

0

6

12

18

NIVO + IPI 74

59

46

34

26

17

52

23

13

7

4

No. at risk

NIVO + IPI 229

192

154

111

90

63

48

29

4

0

Chemo 226

182

141

101

69

50

40

18

5

0

4%

Chemo

76

24 30 36 Months

Chemo 42

48

54

14

6

3

0

3

2

1

0

15

MESOTHELIOOM 2021

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