Mangili G - Mito

Roma, dicembre 2015
XXVI MITO MEETING:
Consiglio Direttivo MITO
Presenti
Pignata
Scambia
Scibilia
Fagotti
Greggi
Raspagliesi
Ferrandina
Mangili
Salerno
Centri e soci
 156 centri MITO (Ginecologie ed Oncologie, 2nuovi)
 10 centri MITO (gruppo traslazionale)
 467 soci (6 nuovi)
Nuovi soci MITO-group
• Sara Giovannoni–Oncologia Medica Università ”La Sapienza ” – Roma
• Antonio Gorio- U.O. Ostetricia e ginecologia Fondazione Poliambulanza- Brescia
• Giovanni Stellato- U.O. C. Ginecologia oncologica INT-Fondazione ” G. Pascale ” – Napoli
• Angela Maria Trujillo-U.O.C. Oncologia medica Uro-ginecologica INT-Fondazione
”G.Pascale ” – Napoli
• Margherita Tambaro-U.O.C. Oncologia medica Uro-ginecologica INT-Fondazione ”G.Pascale
” – Napoli
• Francesca Falcone-U.O. Ostetricia e ginecologia -Seconda Università degli Studi di Napoli
MITO Pub
Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-nonmutated advanced or metastatic endometrial cancer: a non-randomised, openlabel, two-group, two-stage, phase 2 study.
Konecny GE, Finkler N, Garcia AA, Lorusso D, Lee PS, Rocconi RP, Fong PC, Squires M,
Mishra K, Upalawanna A, Wang Y, Kristeleit R. Lancet Oncol. 2015 Jun;16(6):686-94.
Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinumresistant or platinum-refractory advanced ovarian cancer (MITO 11): a
randomised, open-label, phase 2 trial.
Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM,
Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M,
Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M,
Gallo C, Perrone F; MITO 11 investigators. Lancet Oncol. 2015 May;16(5):561-8.
Is the endometrial evaluation routinely required in patients with adult granulosa
cell tumors of the ovary?
Ottolina J, Ferrandina G, Gadducci A, Scollo P, Lorusso D, Giorda G, Breda E,
Savarese A, Candiani M, Zullo F, Mangili G. Gynecol Oncol. 2015 Feb;136(2):230-4.
MITO Pub
 Gynecologic Cancer InterGroup (GCIG) consensus review for mucinous
ovarian carcinoma.
Ledermann JA, Luvero D, Shafer A, O'Connor D, Mangili G, Friedlander M, Pfisterer J,
Mirza MR, Kim JW, Alexandre J, Oza A, Brown J. Int J Gynecol Cancer. 2014 Nov;24(9
Suppl 3):S14-9
 Gynecologic Cancer InterGroup (GCIG) consensus review for high-grade
undifferentiated sarcomas of the uterus.
Pautier P, Nam EJ, Provencher DM, Hamilton AL, Mangili G, Siddiqui NA, Westermann
AM, Reed NS, Harter P, Ray Coquard I.Int J Gynecol Cancer. 2014 Nov;24(9 Suppl
3):S73-7.
 Gynecologic Cancer InterGroup (GCIG) consensus review for clear cell
carcinoma of the uterine corpus and cervix.
Hasegawa K, Nagao S, Yasuda M, Millan D, Viswanathan AN, Glasspool RM, DevouassouxShisheboran M, Covens A, Lorusso D, Kurzeder C, Kim JW, Gladieff L, Bryce J,
Friedlander M, Fujiwara K. Int J Gynecol Cancer. 2014 Nov;24(9 Suppl 3):S90-5.
MITO Pub
Carboplatin and pegylated liposomal doxorubicin versus carboplatin and
paclitaxel in very platinum-sensitive ovarian cancer patients: results from a
subset analysis of the CALYPSO phase III trial.
Mahner S, Meier W, du Bois A, Brown C, Lorusso D, Dell'Anna T, Cretin J, Havsteen H,
Bessette P, Zeimet AG, Vergote I, Vasey P, Pujade-Lauraine E, Gladieff L, Ferrero A. Eur J
Cancer. 2015 Feb;51(3):352-8.
 Gynecologic Cancer InterGroup (GCIG) consensus review for carcinoid tumors
of the ovary.
Reed NS, Gomez-Garcia E, Gallardo-Rincon D, Barrette B, Baumann K, Friedlander M,
Kichenadasse G, Kim JW, Lorusso D, Mirza MR, Ray-Coquard I. Int J Gynecol Cancer. 2014
Nov;24(9 Suppl 3):S35-41.
 Trophoblastic disease review for diagnosis and management: a joint report
from the International Society for the Study of Trophoblastic Disease,
European Organisation for the Treatment of Trophoblastic Disease, and the
Gynecologic Cancer InterGroup.
Mangili G, Lorusso D, Brown J, Pfisterer J, Massuger L, Vaughan M, Ngan HY, Golfier F,
Sekharan PK, Charry RC, Poveda A, Kim JW, Xiang Y, Berkowtiz R, Seckl MJ. Int J Gynecol
Cancer. 2014 Nov;24(9 Suppl 3):S109-16.
MITO Pub
Trophoblastic disease review for diagnosis and management: a joint report from the
International Society for the Study of Trophoblastic Disease, European Organisation
for the Treatment of Trophoblastic Disease, and the Gynecologic Cancer InterGroup.
Mangili G, Lorusso D, Brown J, Pfisterer J, Massuger L, Vaughan M, Ngan HY, Golfier F, Sekharan PK,
Charry RC, Poveda A, Kim JW, Xiang Y, Berkowtiz R, Seckl MJ.
Int J Gynecol Cancer. 2014 Nov;24
Gynecologic Cancer InterGroup (GCIG) consensus review for ovarian and primary
peritoneal low-grade serous carcinomas. Gourley C, Farley J, Provencher DM, Pignata S,
Mileshkin L, Harter P, Maenpaa J, Kim JW, Pujaide-Lauraine E, Glasspool RM, Ray-Coquard I, Gershenson
D. Int J Gynecol Cancer. 2014 Nov;24(9 Suppl 3): S9-13.
Management of bilateral malignant ovarian germ cell tumors: a MITO-9 retrospective
study.
Sigismondi C, Scollo P, Ferrandina G, Candiani M, Angioli R, Viganò R, Scarfone G, Mangili G.
Int J Gynecol Cancer. 2015 Feb;25(2):203-7.
 Gynecologic Cancer Intergroup (GCIG) consensus review for ovarian germ cell tumors.
Brown J, Friedlander M, Backes FJ, Harter P, O'Connor DM, de la Motte Rouge T, Lorusso D, Maenpaa
J, Kim JW, Tenney ME, Seckl MJ. Int J Gynecol Cancer. 2014 Nov;24(9 Suppl 3):S48-54.
Randomized, Double-Blind, Phase III Trial of Olaparib vs. Placebo in
Patients with Advanced FIGO Stage IIIB – IV High Grade Serous or
Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer treated
with standard First-Line Treatment, Combining Platinum-Taxane
Chemotherapy and Bevacizumab Concurrent with Chemotherapy and
in Maintenance.
10

Europe: ENGOT Groups
France
Austria
Denmark
Finland
Belgium
Sweden
Germany
Italy

Spain
Japan: GOTIC
11
12
AGO-OVAR 2.28
*C 20 mg + O 300mg bd
R
1:1:1
N=90
*C 30 mg + O 200mg bd
Platinum CT +/- bev
IDMC/TSC criteria:
Take forward C20 + O 300mg unless underperforming
(ORR; DAE, dose reductions)
Phase III part
N = 656; 80% power; 5% significance; upper HR CI 1.23
assuming mPFS 11 mo (CT) and 11.25 mo (C+O)
*Blinded
Winner or C 20
mg + O 300mg bd if
similar
Additional n = 596
PFS 1
HGSOC/E or BRCAm
PFI > 6 mo
Response to prior
platinum CT
•2nd -3rd line
• ECOG 0-2
•Prior bev allowed
IDMC/TSC review ORR; safety
“Semi-Blinded” Run-in phase
followed by open label phase III
PRR n=100
PFI 3-6 mo
C 20 (30) mg od +
O 300 (200) mg bd
Rand. 1:1
n= 696
Platinum based CT +/bev as per label
PSR – primary population
PRR – exploratory population: endpoints: translational aspects, safety, efficacy
Platinum based CT
followed by olaparib
if BRCAm (“as per
label”)
C+O
or
physicians choice
PFS2 (Exploratory)
PSR n=596
HGSOC/E or BRCAm
PFI > 6 mo
•2nd -3rd line
• ECOG 0-2
• Prior bev allowed
“Winner” of safety
run in
Primary Endpoint: PFS in
PSR (primary population)
AGO-OVAR 2.28
Study Design
BGOG Farletuzumab
Study
Objectives
Primary:

Farletuzumab has superior efficacy compared to placebo in improving
progression-free survival (PFS) as determined by RECIST 1.1 when added to
1 of 2 standard chemotherapy regimens (carboplatin plus paclitaxel or
carboplatin plus PLD) in subjects with platinum-sensitive ovarian cancer in
first relapse who have a CA125 ≤ 3x the upper limit of normal (ULN) at study
entry.
Secondary:





Overall survival (OS) in this population
To assess the effect of Farletuzumab in prolonging second platinum-free
interval longer than first platinum-free interval
To assess the effect of farletuzumab on best objective response (OR) rate,
time to response (TTR) and duration of response (DR) by RECIST 1.1 criteria
To assess the safety and tolerability of Farletuzumab
To assess the pharmacokinetics and exposure-response relationships between
Farletuzumab and PFS and OS
Coordinating investigator: Prof Dr. Ignace Vergote
Patients (# 120) with histologically or cytologically confirmed squamous,
adenosquamous or adenocarcinoma of the cervix
Advanced stage (FIGO stage IVB)
OR Recurrent/persistent disease
1:1 Randomization IXRS
Nintedanib 200 mg p.o. BID
Placebo p.o. BID
PLUS
PLUS
Paclitaxel 175 mg/m2 + carboplatin
AUC5
Paclitaxel 175 mg/m2 + carboplatin
AUC5
Every 21 days for 6 cycles
Every 21 days for 6 cycles
Nintedanib monotherapy up to 120
weeks
Placebo monotherapy up to 120 weeks
A Phase 3, Multicenter, Randomized, Open-label Study
of Avelumab* (MSB0010718C) Alone or in
Combination with Pegylated Liposomal Doxorubicin
Vs. Pegylated Liposomal Doxorubicin Alone in Patients
with Platinum-Resistant/Refractory Ovarian Cancer
*Avelumab is the proposed international nonproprietary name (INN) for the antiPD-L1 monoclonal antibody (MSB0010718C).
B9991009: Protocol Overview
Pre Trial Assessment Visit - Date Year
A Phase 3, Randomized, Double-Blind, Placebo-Controlled,
Multicenter Study of Niraparib Maintenance Treatment in Patients
with HRD-Positive Advanced Ovarian Cancer Following Response
on Front-Line Platinum-Based Chemotherapy
ENGOT-ov 26 (PRIMA study)
Leading Group: GEICO
Chair: A. González
Co-Chair: B. Monk
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DRAFT – Subject to Further Review – Company Confidential and Proprietary – Internal Use Only
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