IMPORTANT DISCLAIMERS
This material is intended for AZ Medical personnel only. Not for promotional use. Any external communication, data discussion, distribution or other dissemination must be supported by AZ global and local promotional guidance, relevant
nominated signatory approval and regulatory practices and policies.
The information provided here includes details of indications that may be off-label and are for scientific medical exchange purposes only. AstraZeneca does not, under any circumstances, promote its products for off-label or unapproved uses.
SOLO-1Olaparib maintenance therapy in patients with newly diagnosed advanced
ovarian cancer following platinum-based chemotherapy
SOLO-1
There remains a significant unmet need for newly diagnosed ovarian
cancer1
1. Ledermann, J. A. et al. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 24 Suppl 6, vi24-32 (2013) 2. Bookman, M. A. et al. J. Clin. Oncol. 27, 1419–1425 (2009); 3. Burger, R. A. et al. N. Engl. J. Med. 365, 2473–2483 (2011); 4. Perren, T. J. et al. N. Engl. J. Med. 365, 2484–2496 (2011); 5. de Angelis R et al. Lancet Oncol 2014;15:23-34.
There is a significant need for better frontline treatment to improve
outcomes for women with ovarian cancer1-5
~70% of women relapse within 3
years of first line treatment1
38%5-year survival rate5
10-18 monthsMedian progression-free
survival2,3,4
Platinum-based
chemotherapy
Bevacizumab
4
20 months
Cure Goal Palliation
HighToxicity
acceptanceLow
Less important Convenience More important
Treatment considerations
First-line treatment Recurrent disease
15% still alive, disease free, at 10 years
When a women is diagnosed with advanced epithelial ovarian
cancer, the goal of firstline treatment is to achieve a cure
SOLO-1 is the first Phase III trial to investigate maintenance therapy
with a PARP inhibitor in newly diagnosed ovarian cancer
*Upfront or interval attempt at optimal cytoreductive surgery for stage III disease and either biopsy and/or upfront or interval cytoreductive surgery for stage IV diseaseBICR = blinded independent central review; ECOG = Eastern Cooperative Oncology Group; FACT-O = Functional Assessment of Cancer Therapy – Ovarian Cancer; FIGO = International Federation of Gynecology and Obstetrics; HRQoL = health-related quality of life; PFS = progression-free survival; PFS2 = time to second progression or death; RECIST = Response Evaluation Criteria in Solid Tumours; TOI = Trial Outcome Index; PARP = poly (ADP-ribose) polymerase; BRCAm = BRCA gene mutationhttps://clinicaltrials.gov/ct2/show/NCT01844986 (accessed October 2018)
SOLO-1 is a global randomised multicentre placebo controlled Phase III study
• Newly diagnosed, FIGO
stage III–IV, high-grade
serous or endometrioid
ovarian, primary
peritoneal or fallopian tube
cancer
• Germline or somatic
BRCAm
• ECOG performance status
0–1
• Cytoreductive surgery*
• In clinical complete
response or partial
response after platinum-
based chemotherapy
Olaparib 300 mg bid
(N=260)
Placebo
(N=131)
2:1 randomisation
• Study treatment
continued until
disease progression
• Patients with no
evidence of disease
at 2 years stopped
treatment
• Patients with a
partial response at 2
years could
continue treatment
Primary endpoint
• Investigator-assessed PFS
(modified RECIST 1.1)
Secondary endpoints
• PFS using BICR
• PFS2
• Overall survival
• Time from randomisation to first
subsequent therapy or death
• Time from randomisation to
second subsequent therapy or
death
• HRQoL (FACT-O TOI score)
Stratified by response
to platinum-based
chemotherapy
2 years’ treatment if no evidence of disease
Ad esclusivo uso interno Medical Affairs
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 ObstetricsMoore 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 (%)
0
1
Missing
200 (76.9)
60 (23.1)
0
105 (80.2)
25 (19.1)
1 (0.8)
Primary tumour location, N (%)
Ovary
Fallopian tubes
Primary peritoneal
Other‡
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 (%)
III
IV
220 (84.6)
40 (15.4)
105 (80.2)
26 (19.8)
8
More than 50% of patients in the olaparib arm completed protocol-
defined treatment
DCO: May 2018IQR = 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 reasonsDCO: May 2018; Median duration of treatment: olaparib 24.6 months; placebo 13.9 monthsIQR = interquartile range1. 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 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
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 patients
Response to previous chemotherapy
Complete response
Partial response
ECOG performance status at baseline
Normal activity
Restricted activity
Baseline CA-125 value
≤ULN
>ULN
gBRCA mutation type by Myriad testing
BRCA1
BRCA2
BRCA1/2 (both)
Negative
Age
<65 years
≥65 years
Stage of disease at initial diagnosis
Stage III
Stage IV
Following debulking surgery prior to study entry
Residual macroscopic disease
No 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)
0/3
3/7 (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)
0/0
1/1 (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
14
Olaparib Placebo
Events, N (%) 69 (26.5) 52 (39.7)
Median PFS2
(months)NR 41.9
HR=0.50
95% 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
sti
ga
tor-
as
se
ss
ed
pro
gre
ss
ion
-fre
e s
urv
iva
l (%
)
Months since randomisationNo. at risk
Olaparib
Placebo
Olaparib
Placebo
260
131
239
122
231
113
229
108
225
100
216
92
204
88
194
79
177
73
168
68
163
63
140
55
111
44
61
18
48
11
13
3
5
1
0
0
0
0
0
0
246
126
In 2nd line, PARP inhibitor was
used in 33/94 (35%) and 10/91
(11%) of patients who received a
subsequent therapy in the placebo
and olaparib arms respectively
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 2018A 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 hospitalisationAE = adverse event; CTCAE = Common Terminology Criteria for Adverse Events; DCO = data cut-off; SAE = serious adverse event1. 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)
16
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
17
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)
11,5
26,9
3,8
19,2
24,6
10
14,6
41,5
37,7
23,1
25,4
26,2
27,7
34,2
38,8
40.0
63,5
77,3
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
19
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
interruption52 17 45 18
% with AE leading to dose reduction 29 3 25 3
% with AE leading to discontinuation 12 2 11 2
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
21
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
Ad esclusivo uso interno Medical Affairs
22
23
24
25
26