Ovaio: novità
Vanda Salutari
Ginecologia Oncologica Fondazione Policlinico Gemelli IRCCS
e-mail:
[email protected]
• Trattamento delle pazienti anziane
• PARP-i
• Nuove combinazioni
OVARIAN CANCER: WHICH SCENARIOS IN THE VERY NEXT and NEXT FUTURE?
Competitors
Novel drugs and/or
‘‘team drugs’’?
Integration Surgery/Biology/
New Drugs
New toxicities
Administrative issues
New tests
Requirement of the best sequence(s)?
PARP inhibitors in ovarian cancer:
current status and future promise
OLAPARIB (Lynparza ®)
FDA approved: mantainance therapy in platinum sensitive relapse high grade ovarian cancer + Deleterious BRCA mutation associated with advanced ovarian cancer EMA approved: mantainance therapy in BRCA + platinum sensitive relapse high grade ovarian cancer
NIRAPARIB (Zejula®)
FDA + EMA approved:
mantainance therapy in platinum sensitive relapse high grade ovarian cancer
RUCAPARIB (Rubraca®) FDA approved:
Deleterious BRCA
mutation associated with advanced ovarian cancer
VELIPARIB
TALAZOPARIB
Randomized
studies SOLO 3 ARIEL 4
Confidential / For Internal TESARO Use Only / Not for Distribution
25
Dosing modification in PRIMA: background
Confidential / For Internal TESARO Use Only / Not for Distribution
26
Grade ≥3 Hematological toxicity decreased after
dose individualization
Confidential / For Internal TESARO Use Only / Not for Distribution
27
PRIMA dose reduction: comparison of tolerance
PRIMA (pre-amendement) (%)
PRIMA (post amendement) (%)
Dose interruption
60 50.6
Dose reduction
51.6 39.7
Discontinuation (tAE)
7.5 10.5
G3 anemia
22.7 13.8
G3 neutropenia
10 6.1
G3 piastrinopenia
23.5 9.7
G4 piastrinopenia
16.8 3.6
Nausea (any grade)
48.6 40.5
Fatigue (any grade)
31.4 30
Exploiting re-challenge of PARP-inhibitors
Immunotherapy in ovarian cancer:
fake news or the real deal?
What’s wrong with
Ovarian Cancer?
What are biomarkers in use and under study?
Presented By Kathleen Moore at 2019 ASCO Annual Meeting
Slide 2
Presented By Oliver Dorigo at 2019 ASCO Annual Meeting
Combination of niraparib and bevacizumab versus niraparib alone <br />as treatment of recurrent platinum-sensitive ovarian cancer: <br />A randomized controlled chemotherapy-free study<br /><br />ENGOT-OV24/NSGO-AVANOVA2
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
Background
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
ENGOT-OV24 / NSGO-AVANOVA2 trial design
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
Patient enrollment and disposition
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
Primary endpoint: PFS in the ITT population
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
PFS by BRCA status
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
Overall response and disease control rates
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
Summary of adverse events
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
Patient-reported outcomes
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
Conclusions
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
Athena First ENGOT OV43 Duo-O
Sponsor Clovis Tesaro Merck Astra Zeneca
Group leader GOG(NCRI) GINECO BGOG AGO
Randomisation Maintenance Upfront Upfront Upfront
Bev in Standardarm No Optional Optional Yes
Exp. Arm - Ruca-Nivolu
- Ruca - Nivolu
- Nira - Nira + O42
BRCA+: Ola + Pembro BRCA-: Pembro Pembro+Ola
- Durva - Durva+Ola
NACT allowed Yes Yes Yes Yes
RT=0 CR/NED after CT No Yes Yes
Endpoint PFS PFS PFS+OS PFS
What is the best biomarker?
The answer remain in the results of the plethora of ongoing trials
57
PFS by stratification factors: Chemotherapy-free interval
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
PFS by stratification factors: HRD status
Presented By Mansoor Mirza at 2019 ASCO Annual Meeting
