Neoplasie
Ginecologiche
Teresa Pira
UO Oncologia e CPDO
Olbia
THE LAST YEAR UPDATES
Epitelial Ovarian Cancer
• Newly diagnosed ovarian cancer
• Relapsed ovarian cancer
There remains a significant unmet need for newly diagnosed ovarian cancer 1
•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 cancer 1-5
~70%
of women relapse within 3 years of first
line treatment 1
38%
5-year survival rate 5
10-18 months
Median progression- free survival 2,3,4
Platinum- based
chemothera py
Bevacizuma b
Ad esclusivo uso interno Medical Affairs
Advanced ovarian cancer:
A ‘chronic’ disease with multiple relapses
PFI: platinum-free interval or duration of disease control without chemotherapy.
du Bois a, Pfisterer J. Zentralbl Gynakol. 2004;126:312-4.
*
Time (months)
First-line chemotherapy
Platinum-sensitive relapses
Occlusion
Symptoms
PFI: 12 months
Platinum-resistant relapses
8 months
4 months
Surgery
Ovarian cancer is not a single disease
Romero I et al.
Endocrinology 2012; 153:
1593-1602
70 %
2% 15% 5%
5%
High Grade Serous Ovarian Cancer is a disease
of Homologous Ricombination Disfunction
BRCA, breast cancer susceptibility gene; BRCAmut, BRCA mutation; PARP, poly(ADP) ribose polymerase.
1. Mirza MR et al. N Engl J Med 2016; 375 (22): 2154–2164. 2. Ledermann J et al. Lancet Oncol 2014; 15 (8): 852–861.3. Coleman RL et al. Lancet 2017; 390 (10106): 1949–1961. 4. Tesaro, Inc. ZEJULA™ – package insert; 2017. 5. AstraZeneca Pharmaceuticals LP. Lynparza™ – package insert; AstraZeneca Pharmaceuticals LP, Wilmington, USA, 2017. 6. AstraZeneca UK Ltd. Lynparza™ – product information; AstraZeneca UK Ltd. Waltham, MA: TESARO, Inc;
2017. 7. Clovis Oncology UK Ltd. Rubraca® 200 mg / 250 mg / 300 mg film-coated tablets – summary of product characteristics. Clovis Oncology UK Ltd., Cambridge, May 2018. 8. Clovis Oncology, Inc. Rubraca® – prescribing information; April 2018.
PARP inhibitor maintenance therapy is
changing clinical practice in ovarian cancer
USA Europe
Indicated as maintenance therapy
4Indicated as maintenance therapy
4Niraparib
NOVA trial, 2016
1Indicated as maintenance therapy
6Indicated as maintenance
therapy for patients with BRCAmut disease
5Olaparib
Study 19, 2014
2Indicated as maintenance therapy
8Not indicated as maintenance therapy
7Rucaparib
ARIEL3 study, 2017
3Current approval status of PARP inhibitors as maintenance therapy for recurrent ovarian cancer:
In clinical studies, PARP inhibitors have demonstrated improved progression-free
survival compared with placebo
1–3+11,5 +8,2
Karam A et al. Ann Oncol 2017
Until a year ago the first-line systemic treatment was an unmet
clinical need
PFS, progression-free survival; OS,
overall survival
In the last 12 months…….
FRONT-LINE
Looking at the scenario in Ovarian Cancer Treatment post ESMO 2018
GOG 218
Chemo + bevacizumab
ICON7
Chemo + bev + olaparib
PAOLA 1?
WT M
+
Chemo→ Chemo +
bevacizumab
AURELIA platinum resistant OCEANS
platinum sensitive Disease
progression
Universal BRCA testing Stage IIIb–IV
Chemo → olaparib
SOLO1
Niraparib
1 L
2 L
3 L
Chemo ± beva
(Mito 16-MaNGO-02 positive
)
But this is all changed in ESMO 2019
∆ 11.5m
∆ 5.6m
BRCAm=BRCA mutation; CI=confidence interval; gBRCAm=genomic BRCA mutation; HR=hazard ratio; PARPi=poly(ADP ribose) polymerase inhibitor; PFS=progression free survival; PSR=platinum sensitive recurrent 1. Liu J et al. Annals of Oncology 0: 1–7, 2019; 2. Mirza M et al. J Clin Oncol 2019. 37 (suppl.: abstract 5505)
