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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