1. MAINTENANCE THERAPY WITH PARP INHIBITORS
Prof Dr Sven Mahner, MD
Chair and Director
Department of Obstetrics & Gynaecology University Hospital Munich,
Ludwig-Maximilians-University, Munich, Germany
ESMO 2018
Munich, Germany

2. Maintenance therapy: Understanding the possibilities
Maintenance therapy is given to sustain the disease control achieved with initial treatment
Key considerations for maintenance therapy ? ?
Tolerability profile of the treatment
Criteria for initiating maintenance therapy ? ?
Characteristics of a successful maintenance therapy
Patient quality of life

3. Should we still do “Watch & Wait”?
Fear of disease recurrence is a psychological burden
Survivors (%)
∼50% women with early and advanced stage ovarian cancer fear disease recurrence2
Psychological burden may increase use of medication and health services1
Fatigue, nausea, vomiting, and poor sleep are associated with a reduction in QoL and increased fear of recurrence2
Uncertainty about and perceived risk of recurrence are two key fears in cancer survivors3
Follow-ups can trigger fear, but close and frequent monitoring can provide reassurance3
Psychological assessments of early-stage ovarian cancer survivors (N=58)1
PTSD, post-traumatic stress disorder
1. Matulonis UA, et al. Int J Gynecol Cancer 2008;18: ; 2. Mirabeau-Beale KL, et al. Gynecol Oncol 2009;114: ; 3. Kyriacou J, et al. Can Oncol Nurs J 2017;27:

4. What do patients expect from maintenance therapy?
Survey of 1,954 patients
Primary / Recurrence
<70 / >70
Increasing the chance of cure
Improvement of QoL
No deterioration of QoL
Delaying the tumour progression
Shrinking the tumour
Decrease of CA-125
Other
Increasing the chance of cure
Improvement of QoL
No deterioration of QoL
Delaying the tumour progression
Shrinking the tumour
Decrease of CA-125
Other ** ** * * ** * 0%
15%
30%
45%
60%
75% 0%
15%
30%
45%
60%
75%
>70
Recurrence
Primary
18-70
*p<0.001; **p<0.05
QoL, quality of life
Sehouli J, et al. EXPRESSION IV/ESGO 2017.

5. What duration of maintenance therapy is acceptable?
Survey of 1,954 patients
Primary / Recurrence*
<70 / >70
until tumour progression
48-60 months
24-36 months
18-24 months
12-18 months
6-12 months
until tumour progression
48-60 months
24-36 months
18-24 months
12-18 months
6-12 months
0% % 20% 30% 40% 50%
0% % % % % %
Recurrence
Primary
>70
18-70
*p<0.001
Sehouli J, et al. EXPRESSION IV/ESGO 2017.

6. The evidence: ENGOT-OV16 / NOVA
Recurrent ovarian, fallopian tube or primary peritoneal cancer following CR or PR to second-line or later platinum-based chemotherapy (N=553)
gBRCAmut (N=203)
2:1 Randomisation
Non-gBRCAmut (N=350)
2:1 Randomisation
Niraparib 300 mg QD
Placebo QD
Niraparib 300 mg QD
Placebo QD
Endpoint assessment
Endpoint assessment
Primary endpoint: PFS
Radiologic disease progression
Clinical signs and symptoms and increasing CA-125
Increasing CA-125 and additional diagnostic tests OR
Progression measured by:
BRCA, breast cancer gene; PFS, progression free survival; ENGOT, European Network for Gynaecological Oncological Trial groups; gBRCAmut, germline BRCA mutation
Mirza MR, et al. N Engl J Med 2016;375:

7. PFS, non-gBRCA cohort (N=350)
Niraparib significantly increased PFS vs placebo – in gBRCA and non-gBRCA cohorts
PFS, gBRCA cohort (N=203)
PFS, non-gBRCA cohort (N=350)
1.0
0.8
0.6
0.4
0.2
PFS probability
Time (months) 6 12 18 24
HR = 0.27
(95% CI: 0.17–0.41) p < 0.001
1.0
0.8
0.6
0.4
0.2
PFS probability
Time (months) 6 12 18 24
HR = 0.45
(95% CI: 0.34–0.61) p < 0.001
Niraparib
Niraparib
PFS 21.0 months
PFS 9.3 months
Placebo
Placebo
PFS 5.5 months
PFS 3.9 months
PFS, progression free survival; HR, hazard ratio; CI, confidence interval; BRCA, breast cancer gene; gBRCA, germline BRCA mutation; non-gBRCA, no germline BRCA mutation
Mirza MR, et al. N Engl J Med 2016;375(22):

8. Published PFS results in maintenance therapy studies
Anti-angiogenesis
BRCA status not determined
PARP inhibition
gBRCA patients
PARP inhibition
non-gBRCA patients
21.0 months
PFS
9.3 months
PFS
Chemotherapy 6 months
Chemotherapy 6 months
GOG2135
OCEANS6
Phase 3
N=337
N=242 5 10 15
Δ3.4
Δ4.0
8.4
10.4
13.8
12.4
N=377
8.8
11.8
Δ3.0
MITO16B7
Chemotherapy 6 months 21
N=138
9.3
Phase 3
NOVA1
N=234
HR 0.628
HR 0.27
HR 0.45
5.5
N=65
Δ15.5
3.9
Δ5.4
N=116
11.2
N=74
7.4
N=57
Phase 2
Study 192
HR 0.48
HR 0.18
4.3
N=62
Δ6.9
HR 0.54
5.5
Δ1.9
N=61
N=202
Phase 3
SOLO23
5.5
N=80
19.1
N=196
HR 0.51
not studied
Δ13.6
N=203
HR 0.30
Phase 3
ARIEL34
16.6
N=130
5.4
N=66
not studied as a cohort
HR 0.23
Δ11.2 5 10 15 20 25 5 10 15 20
Treatment Placebo
PFS, progression free survival; BRCA, breast cancer gene; gBRCAmut, germline breast cancer gene mutated
1. Mirza MR, et al. N Engl J Med 2016;375: ; 2. Ledermann J, et al. Lancet Oncology 2014;15: ; 3. Pujade-Lauraine E, et al. Lancet Oncology 2017;18: ;
4. Coleman RL, et al. Lancet 2017;390: ; 5. Coleman et al. Lancet Oncology 2017;18: ; 6. Aghajanian C, et al. J Clin Oncol 2012;30:
7. Pignata S, et al. J Clin Oncol 2018;36:(suppl; abstr 5506).