Presentazione dati SOLO 1
Rocco De Vivo
U.O. di Oncologia Medica
AULSS8 “BERICA” - Vicenza
Ospedale San Bortolo
3
4
The majority of patients receive multiple lines of cytotoxic chemotherapy which is associated with cumulative toxicity and decreasing periods of remission1-4
PFS = progression-free survival; CA-125 = cancer antigen 125; † = Common indicator of fatality
• 1. Markman, M. et al. The Oncologist. 2000;5(1):26–35; 2. Hanker LC, et al. Ann Oncol. 2012;23(10):2605–2612; 3. Armstrong, D. K. The Oncologist 7, 20–28 (2002); 4.Fotopoulou, C. Eur. J. Cancer Suppl. 12, 13–16 (2014)
CA–125 l
ev
el
1ST LINE 5TH LINE
* Bowel obstruction
†
2ND LINE 3RD LINE 4TH LINE
18.2 months 10.2 months 6.4 months
Surgery
5.6 months 4.4 months
Symptoms
PFS PFS PFS PFS PFS
Time
6
Analysis
• Prespecified analysis at 206 PFS events
• 90% power at a two-sided significance level of 5%
• Target HR for PFS of 0.62 (median of 21 months
[olaparib] vs. 13 months [placebo])
Protocol amended due to slower than projected
event rate – primary PFS analysis conducted
after ≈196 events OR last patient randomised
had the opportunity to be on study for ≥36
months
Patients in SOLO-1 had a minimum follow-up of 3 years
• HR = hazard ratio; PFS = progression-free survival• Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
2013 2014 2015 2016 2017 2018
First patient in:
3 Sep 2013Last patient in:
6 Mar 2015
Data cut-off:
17 May 2018
Minimum follow-up period of 3 years
Baseline characteristics were well balanced between treatment groups
• *Clinical complete response was defined as no evidence of (RECIST) measurable or non-measurable disease on the post-treatment scan and a normal CA-125 level.• †Partial response was defined as a ≥30% reduction in tumour volume from the start to the end of chemotherapy or no evidence of disease on the post-treatment scan, but with a CA-125 level which had not decreased to within the normal range• ‡Other includes ovary, fallopian tube, peritoneum, and omentum (N=1), ovary and peritoneum (N=1) and tubo-ovary (N=1)• ECOG = Eastern Cooperative Oncology Group; FIGO = International Federation of Gynecology and Obstetrics• Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print
Characteristic Olaparib (N=260) Placebo (N=131)
Median age, years (range) 53.0 (29–82) 53.0 (31–84)
Response after platinum-based chemotherapy, N (%)Clinical complete response*Partial response†
213 (81.9)47 (18.1)
107 (81.7)24 (18.3)
ECOG performance status, N (%)01Missing
200 (76.9)60 (23.1)
0
105 (80.2)25 (19.1)
1 (0.8)
Primary tumour location, N (%)OvaryFallopian tubesPrimary peritonealOther‡
220 (84.6)22 (8.5)15 (5.8)3 (1.2)
113 (86.3)11 (8.4)7 (5.3)
0
FIGO stage, N (%)IIIIV
220 (84.6)40 (15.4)
105 (80.2)26 (19.8)
8
Characteristic Olaparib (N=260) Placebo (N=131)
Baseline CA-125 level, N (%)≤ULN>ULNMissing
247 (95.0)13 (5.0)
0
123 (93.9)7 (5.3)1 (0.8)
Histology, N (%)SerousEndometrioidMixed serous/endometrioid
246 (94.6)9 (3.5)5 (1.9)
130 (99.2)0
1 (0.8)
BRCA mutation,§ N (%)BRCA1BRCA2Both BRCA1 and BRCA2
191 (73.5)66 (25.4)
3 (1.2)
91 (69.5)40 (30.5)
0
Baseline characteristics were well balanced between treatment groups
• §Myriad/BGI or locally reported; the five patients from China had germline BRCA mutation testing performed within China, using the BGI test. Central germline testing confirmed that 388/391 patients had a BRCA1/2 mutation, 1 patient had a BRCA variant of uncertain significance, and 2 patients were BRCA wild-type. Foundation Medicine testing confirmed that the two germline BRCA wild-type patients had somatic BRCA mutations• ULN = upper limit of normal per institutional standard.• Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print
9
Two thirds of patients had upfront surgery
• Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print [supplementary appendix]
History of cytoreductive surgery, N (%) Olaparib (N=260) Placebo (N=131)
Upfront surgery
Residual macroscopic disease
No residual macroscopic disease
Unknown
Interval cytoreductive surgery
Residual macroscopic disease
No residual macroscopic disease
No surgery
161 (61.9)
37 (23.0)
123 (76.4)
1 (0.6)
94 (36.2)
18 (19.1)
76 (80.9)
4 (1.5)
85 (64.9)
22 (25.9)
62 (72.9)
1 (1.2)
43 (32.8)
7 (16.3)
36 (83.7)
3 (2.3)
Characteristic Olaparib (N=260) Placebo (N=131)
Agents administered during platinum-based chemotherapy prior to
randomisation
Bevacizumab
Carboplatin
Cisplatin
Cyclophosphamide
Docetaxel
Doxorubicin
Doxorubicin hydrochloride
Gemcitabine
Nab-paclitaxel
Paclitaxel
1 (0.4)
241 (92.7)
46 (17.7)
1 (0.4)
15 (5.8)
1 (0.4)
1 (0.4)
2 (0.8)
2 (0.8)
253 (97.3)
0
115 (87.8)
32 (24.4)
0
7 (5.3)
0
0
1 (0.8)
0
130 (99.2)
Number of cycles of platinum-based chemotherapy, N (%)
4
5
6
7
8
9
2 (0.8)
2 (0.8)
198 (76.2)
17 (6.5)
18 (6.9)
23 (8.8)
0
1 (0.8)
106 (80.9)
10 (7.6)
7 (5.3)
7 (5.3)
The majority of patients received carboplatin and paclitaxel for 6 cycles
• Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print [supplementary appendix]
11
More than 50% of patients in the olaparib arm completed protocol-defined treatment
• DCO: May 2018
• IQR = interquartile range • 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print [supplementary appendix]
Olaparib Placebo
Randomised, N 260 131
Treated, N 260 130
Discontinued treatment before 2 years
Completed treatment at 2 years per protocol, N (%)
Continued treatment beyond 2 years Still receiving treatment at data cut-off, N (%)
111 (42.6)
123 (47.3)
26 (10.0)13 (5.0)
92 (70.7)
35 (26.9)
3 (2.3)1 (0.8)
Median (mean) total treatment duration (months) 24.6 (052.0) 13.9 (0.245.6)
Median (IQR) duration of follow-up, months40.7
(34.9–42.9)41.2
(32.2–41.6)
The most common reason for discontinuation was disease progression
• *Other includes study-specific discontinuation criteria, severe non-compliance to protocol and lost to follow-up, among other reasons
• DCO: May 2018; Median duration of treatment: olaparib 24.6 months; placebo 13.9 months
• IQR = interquartile range• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
Olaparib Placebo
Randomised, N 260 131
Treated, N 260 130
Discontinued treatment other than protocol defined stopping rule, N (%)
Objective disease progression
Adverse event
Patient decision
Other*/unknown reason
124 (47.7)
51 (19.6)
30 (11.5)
22 (8.5)
21 (8.1)
94 (72.3)
78 (60.0)
3 (2.3)
2 (1.5)
11 (8.5)
Olaparib reduced the risk of progression or death by 70% vs. placebo1
• DCO: May 2018; Median FU: olaparib, 40.7 months placebo, 41.2 months• Analysis was performed after 198 progression events had occurred (in 50.6% of patients)• PFS = progression-free survival; DCO = data cut-off; HR = hazard ratio; CI = confidence interval
• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
After a median follow-up of 41 months, the median PFS had not been reached in the olaparib
arm (vs. 13.8 months in the placebo arm)1
0 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
0
10
20
30
40
50
60
70
80
90
100
3
Inve
sti
ga
tor-
as
se
ss
ed
pro
gre
ss
ion
-fre
e s
urv
iva
l (%
)
Months since randomisation
260
131
229
103
221
82
212
65
201
56
194
53
184
47
172
41
149
39
138
38
133
31
111
28
88
22
45
6
36
5
4
1
3
0
0
0
0
0
0
0
Olaparib
Placebo
240
118
No. at risk
Olaparib
Placebo
Primary endpoint:
investigator-assessed
PFS
Olaparib Placebo
Events, N (%) 102 (39.2) 96 (73.3)
Median PFS (months)
NR 13.8
HR=0.30 95% CI: 0.23, 0.41
p<0.001
Stima PFS: 49.8 mesi vs 13.8 mesi: ∆36,7 mesi
Olaparib reduced the risk of progression or death by 70% vs. placebo1
• DCO: May 2018; Median FU: olaparib, 40.7 months placebo, 41.2 months• Analysis was performed after 198 progression events had occurred (in 50.6% of patients)• PFS = progression-free survival; DCO = data cut-off; HR = hazard ratio; CI = confidence interval
• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
0 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
0
10
20
30
40
50
60
70
80
90
100
3
Inve
sti
ga
tor-
as
se
ss
ed
pro
gre
ss
ion
-fre
e s
urv
iva
l (%
)
Months since randomisation
260
131
229
103
221
82
212
65
201
56
194
53
184
47
172
41
149
39
138
38
133
31
111
28
88
22
45
6
36
5
4
1
3
0
0
0
0
0
0
0
Olaparib
Placebo
240
118
No. at risk
Olaparib
Placebo
Primary endpoint:
investigator-assessed
PFS
Olaparib Placebo
Events, N (%) 102 (39.2) 96 (73.3)
Median PFS (months)
NR 13.8
HR=0.30 95% CI: 0.23, 0.41
p<0.001
60.4% progression
free at 3 years
26.9% progression
free at 3 years
A 3 anni solo il 40% delle pazienti trattate con olaparib ricade, contro il 70% delle pazienti trattate con placebo
There was no obvious change in Kaplan-Meier curves after 2 years in the olaparib group, indicating an apparent enduring treatment benefit1
• DCO: May 2018; Median FU: olaparib, 40.7 months placebo, 41.2 months• Analysis was performed after 198 progression events had occurred (in 50.6% of patients)• PFS = progression-free survival; DCO = data cut-off; HR = hazard ratio; CI = confidence interval
• 1. Moore K et al. Oral presentation LBA7_PR, ESMO (2018); 2. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print
After a median follow-up of 41 months, the median PFS had not been reached in the olaparib
arm (vs. 13.8 months in the placebo arm)2
0 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
0
10
20
30
40
50
60
70
80
90
100
3
Inve
sti
ga
tor-
as
se
ss
ed
pro
gre
ss
ion
-fre
e s
urv
iva
l (%
)
Months since randomisation
260
131
229
103
221
82
212
65
201
56
194
53
184
47
172
41
149
39
138
38
133
31
111
28
88
22
45
6
36
5
4
1
3
0
0
0
0
0
0
0
Olaparib
Placebo
240
118
No. at risk
Olaparib
Placebo
Primary endpoint:
investigator-assessed
PFS
Olaparib Placebo
Events, N (%) 102 (39.2) 96 (73.3)
Median PFS (months)
NR 13.8
HR=0.30 95% CI: 0.23, 0.41
p<0.001
BICR analysis of PFS was consistent with the primary endpoint1
• DCO: May 2018; Median FU: olaparib, 40.7 months placebo, 41.2 months• Data maturity at 38.4%• BICR = blinded independent centralised review; PFS = progression-free survival; DCO = data cut-off; HR = hazard ratio; CI = confidence interval
• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
Olaparib led to a 72% reduction in the risk of disease progression or death vs. placebo1
18
Olaparib Placebo
Events, N (%) 75 (28.8) 75 (57.3)
Median PFS (months)
NR 14.1
HR=0.2895% CI: 0.20, 0.39;
p<0.001
0 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
0
10
20
30
40
50
60
70
80
90
100
3
BIC
R-a
sse
sse
dp
rogr
ess
ion
-fre
e s
urv
ival
(%
)
Months since randomisation
Placebo
Olaparib
260
131
226
97
216
76
206
58
196
50
190
42
178
39
170
37
150
35
137
34
132
28
108
26
82
22
42
6
34
5
3
1
2
0
0
0
0
0
0
0
238
114
No. at risk
Olaparib
Placebo
A consistent benefit was seen across all PFS subgroups1,2
• DCO: May 2018; Median FU: olaparib, 40.7 months placebo, 41.2 months• ECOG = Eastern Cooperative Oncology Group; ULN = upper limit of normal; PFS = progression-free survival; CA-125 = cancer antigen 125; DCO = data cut-off; HR = hazard ratio• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
All patientsResponse to previous chemotherapy
Complete responsePartial response
ECOG performance status at baselineNormal activityRestricted activity
Baseline CA-125 value≤ULN>ULN
gBRCA mutation type by Myriad testingBRCA1BRCA2BRCA1/2 (both)Negative
Age<65 years≥65 years
Stage of disease at initial diagnosisStage IIIStage IV
Following debulking surgery prior to study entryResidual macroscopic diseaseNo residual macroscopic disease
102/260 (39.2)
73/213 (34.3)29/47 (61.7)
75/200 (37.5)27/60 (45.0)
92/247 (37.2)10/13 (76.9)
84/188 (44.7)15/62 (24.2)
0/33/7 (42.9)
85/225 (37.8)17/35 (48.6)
83/220 (37.7)19/40 (47.5)
29/55 (52.7)70/200 (35.0)
96/131 (73.3)
73/107 (68.2)23/24 (95.8)
76/105 (72.4)20/25 (80.0)
89/123 (72.4)7/7 (100.0)
69/91 (75.8)26/39 (66.7)
0/01/1 (100.0)
82/112 (73.2)14/19 (73.7)
79/105 (75.2)17/26 (65.4)
23/29 (79.3)69/98 (70.4)
0.30 (0.23, 0.41)
0.35 (0.26, 0.49)0.19 (0.11, 0.34)
0.33 (0.24, 0.46)0.38 (0.21, 0.68)
0.34 (0.25, 0.46)NC
0.40 (0.29, 0.56)0.20 (0.10, 0.38)
NC
0.33 (0.24, 0.45)0.45 (0.22, 0.92)
0.32 (0.24, 0.44)0.49 (0.25, 0.94)
0.44 (0.25, 0.77)0.33 (0.23, 0.46)
Subgroup
Olaparib 300 mg bid Placebo bidHR (95% CI)
0.2500 0.5000 1.0000 2.00000.0625 0.1250
Olaparib better Placebo better
Number of patients with events/total number of patients (%)
A 50% reduction in the risk of second progression or death was observed in SOLO-11,2
• DCO: May 2018; Median FU: olaparib, 40.7 months placebo, 41.2 months• Data maturity at 30.9%• PFS2 = progression-free survival 2; DCO = data cut-off; HR = hazard ratio; PARP = poly (ADP-ribose) polymerase
• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
This demonstrates that olaparib maintenance does not diminish the benefit conferred by
subsequent therapy
20
Olaparib Placebo
Events, N (%) 69 (26.5) 52 (39.7)
Median PFS2 (months)
NR 41.9
HR=0.5095% CI: 0.35, 0.72;
p<0.001
0 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
0
10
20
30
40
50
60
70
80
90
100
3
Inve
stig
ato
r-as
sess
ed
pro
gre
ssio
n-f
ree
su
rviv
al (
%)
Months since randomisationNo. at risk
Olaparib
Placebo
Olaparib
Placebo
260131
239122
231113
229108
225100
21692
20488
19479
17773
16868
16363
14055
11144
6118
4811
133
51
00
00
00
246126
Efficacy of olaparib was observed beyond a range of efficacy endpoints vs. placebo1,2
• *Time from randomisation to second progression or death; in second line, a PARP inhibitor was used in 33/94 (35%) patients in the placebo arm and 10/91 (11%) patients in the olaparib arm• DCO: May 2018• PFS2 = progression-free survival 2; DCO = data cut-off; HR = hazard ratio; CI = confidence interval• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print 2. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
0 10 20 30 40 50 60
Olaparib (N=260) Placebo (N=131)
Data are immature
40.7
Median not reached
15.1
51.8
51.8Median not reached
41.9
Median overall survival
(21.0% maturity)
HR 0.95
95% CI 0.60, 1.53; p=0.89
Median time to
second subsequent
therapy or death
Median time to first
subsequent
therapy or death
Median PFS2*
(30.9% maturity)
HR 0.50
95% CI 0.35, 0.72; p<0.001
HR 0.45
95% CI 0.32, 0.63; p<0.0001
HR 0.30
95% CI 0.22, 0.40; p<0.0001
Adverse events were mostly mild or moderate in the olaparib arm1,2
• DCO: May 2018• A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose. results in death, is life-threatening. requires inpatient hospitalisation or causes prolongation of existing hospitalisation• AE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; DCO = data cut-off; SAE = serious adverse event• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
Grade ≥3 AEs occurred in 39% of patients in the olaparib arm vs. 19% in the placebo arm
Olaparib (N=260) Placebo (N=130)
Median duration of treatment, months (range) 24.6 (0-52.0) 13.9 (0.2-45.6)
Any AE, N (%) 256 (98.5) 120 (92.3)
Any AE of CTCAE Grade ≥3, N (%) 102 (39.2) 24 (18.5)
Any SAE, N (%) 54 (20.8) 16 (12.3)
22
Most interventions were managed through dose modifications without the need for discontinuation1,2
• DCO: May 2018• AE = adverse event; DCO = data cut-off• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print [supplementary appendix]; 2. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
11.5% of patients in the olaparib arm discontinued treatment due to an AE
23
Olaparib (N=260) Placebo (N=130)
Any AE leading to a dose interruption, N (%) 135 (51.9) 22 (16.9)
Any AE leading to a dose reduction, N (%) 74 (28.5) 4 (3.1)
Any AE leading to discontinuation of treatment, N (%) 30 (11.5) 3 (2.3)
• The most common treatment-emergent AEs leading to discontinuation were
– Nausea (2.3% in the olaparib group vs. 0.8% in the placebo group)
– Anaemia (2.3% in the olaparib group vs. 0% in the placebo group)
The most common AEs reported in patients on olaparib in SOLO-1 were gastrointestinal disturbances, fatigue and anaemia
• *Grouped term• AE = adverse event• 1. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
Olaparib (N=260) Placebo (N=130)
Adverse events (%)
Constipation
Dysgeusia
Neutropenia*
Nausea
Fatigue/asthenia*
Vomiting
Diarrhoea
Arthralgia
100 75 50 25 0 0 25 50 75 100
Anaemia*
0.8
3.8
0.4
21.5
3.1
8.5 4.6
1.5
0.8
1.5
All grades (frequency ≥25%)
Grade ≥3 (frequency ≥5%)
All grades (frequency ≥25%)
Grade ≥3 (frequency ≥5%)
The most common haematological AEs were anaemia and neutropenia1,2
• *Grouped term• AE = adverse event• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. AstraZeneca data on file (2018)
This is consistent with previous trials of olaparib in ovarian cancer
25
Olaparib 300mg bid (N=260) Placebo (N=130)
Adverse events, % Any grade Grade ≥3 Any grade Grade ≥3
Anaemia* 38.8 21.5 10.0 1.5
Neutropenia* 23.1 8.5 11.5 4.6
Thrombocytopenia* 11.2 0.8 3.8 1.5
The safety and tolerability profile for olaparib in SOLO-1 is consistent with previous knowledge despite longer duration of therapy
• *Grouped term• PSR = platinum-sensitive relapse; CTCAE = Common Terminology Criteria for Adverse Events; AE = adverse event• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Pujade-Lauraine E, et al. Lancet Oncol 2017:18(9)1274–1284
SOLO-1 (newly diagnosed BRCAm)1 SOLO-2 (PSR BRCAm)2
Olaparib tablet (N=260) Placebo (N=130) Olaparib tablet (N=195) Placebo (N=99)
Adverse events, % All Grades Grade ≥3 All Grades Grade ≥3 All Grades Grade ≥3 All Grades Grade ≥3
Anaemia* 39 22 10 2 43 19 8 2
Neutropenia* 23 9 12 5 20 5 6 4
Thrombocytopenia* 11 1 4 2 13 1 2 1
Nausea 77 1 38 0 76 3 33 0
Fatigue/asthenia 64 4 42 2 66 4 39 2
Vomiting 40 0.4 15 0.8 38 3 19 1
Diarrhoea 34 3 25 0 33 1 20 0
CTCAE Grade ≥3 39 19 36 18
% with AE leading to dose interruption 52 17 45 18
% with AE leading to dose reduction 29 3 25 3
% with AE leading to discontinuation 12 2 11 2
AEs of special interest were in line with rates seen in previous trials of olaparib1,2
• *The three cases of MDS/AML occurred 1.7–5.7 months after stopping olaparib (duration of olaparib therapy of 14.3–24.9 months); †Including breast cancer (n=3), head and neck cancer (n=1) and thyroid cancer (n=1) in the olaparib group and breast cancer (n=3) in the placebo group• AML = acute myeloid leukaemia; MDS = myelodysplastic syndrome; ILD = interstitial lung disease• 1. Moore K et al. Oral presentation LBA7_PR, ESMO (2018); 2. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print
27
Olaparib (N=260)
Placebo (N=130)
MDS/AML,* N (%) 3 (1.2) 0
New primary malignancies,† N (%) 5 (1.9) 3 (2.3)
Pneumonitis/ILD, N (%) 5 (1.9) 0
MDS / AML rates in SOLO-1 were consistent with prior studies of olaparib in ovarian cancer1-5
• AML = acute myeloid leukaemia; MDS = myelodysplastic syndrome; OC = ovarian cancer; PSR = platinum-sensitive relapse; P3 = Phase III; HER2- = human epidermal growth factor receptor 2; mBC = metastatic breast cancer; gBRCAm = germline BRCA mutation• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print [supplementary appendix]; 3. Gourley, C. et al. J Clin Oncol 35 (poster related to suppl; abstr 5533) (2017); 4. Pujade-Lauraine E, et al. Lancet Oncol 2017:18(9)1274–1284; 5. Robson et al. N Engl J Med. 2017; 377:523-533
28
Trial
AML / MDS rate in
olaparib arm
N
AML / MDS rate in
comparator arm
N
Comparator arm
SOLO-11,2
Newly diagnosed OC, BRCAm3/260 (1.2%) 0/130 (0%) Placebo
SOLO-23
PSR OC, BRCAm4/195 (2.1%) 4/99 (4%) Placebo
Study 194
PSR OC2/136 (1.5%) 1/129 (0.8%) Placebo
Ovarian P3 comparative studies
Combined (monotherapy)9/591 (1.5%) 5/358 (1.4%)
OlympiAD5
HER2- mBC, gBRCAm0/205 (0%) 0/91 (0%)
TPC – capecitabine, eribulin or
vinorelbine
There was no clinically meaningful difference in HRQoL between arms
• *TOI scores range from 0 to 100, with higher scores indicating better HRQoL and a clinically meaningful difference defined as ±10 points• HRQoL = health-related quality of life; TOI = trial outcome index; CI = confidence interval• 1. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
40
Ch
ange
fro
m b
ase
line
in T
OI s
core
Weeks since randomisation
218115
204114
No. at riskOlaparibPlacebo
Olaparib
Placebo
353025201510
5
0
-40-35-30-25-20-15-10
-5
13 25 37 49 61 73 85 97
191104
18691
17975
16361
14451
14149
13742
5
The difference between olaparib and placebo in the mean change from baseline in TOI score over 24
months (−3.00; 95% CI −4.779, −1.216) was
not clinically meaningful
Conclusions
• PFS = progression-free survival; AE = adverse event; HRQoL = health-related quality of life; HR = hazard ratio; BRCAm = BRCA gene mutation• 1. Moore K et al. N. Engl. J. Med. (2018) ePub ahead of print; 2. Moore K et al. Oral presentation LBA7_PR, ESMO (2018)
Maintenance olaparib led to a substantial, unprecedented improvement in PFS in patients with
newly diagnosed, advanced ovarian cancer and a BRCAm, with a difference in median PFS
estimated to be in the region of 3 years1,2
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A 70% reduction in risk of disease progression or death was observed for olaparib vs. placebo-treated patients (HR 0.30; p<0.001)1
• After a median follow up of 41 months, median PFS was not reached on the olaparib arm vs. 13.8 months for placebo with PFS at 3 years: 60.4% vs. 26.9% for olaparib vs placebo1
A reduction in the risk of second progression or death was observed demonstrating that olaparib maintenance does not diminish the benefit conferred by subsequent therapy1
The safety profile is consistent with previous olaparib data with most AEs being mild or moderate in severity and generally not leading to dose reduction or permanent discontinuation1
There was no decrease in HRQoL from baseline for olaparib-treated patients over the 24-month treatment period and no clinically important differences in HRQoL compared with placebo-treated patients1
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