Presentazione dati SOLO 1 - BLOG Project · Presentazione dati SOLO 1 Rocco De Vivo U.O. di Oncologia Medica AULSS8 “BERICA” - Vicenza Ospedale San Bortolo. 3. 4. The majority

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


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)


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



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 (%

)


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:


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


• 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 (%

)


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:


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


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

(%

)


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


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


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


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)


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

30

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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Presentazione dati SOLO 1 - BLOG Project · Presentazione dati SOLO 1 Rocco De Vivo U.O. di Oncologia Medica AULSS8 “BERICA” - Vicenza Ospedale San Bortolo. 3. 4. The majority