XXVI Riunione Nazionale MITO “OVARIAN CANCER AND GYNECOLOGICAL MALIGNANCIES INSIGHTS, DEBATES AND CONTROVERSIES” The MITO 16A&B: Progress Report Gennaro Daniele Unità Sperimentazioni Cliniche Istituto Nazionale Tumori di Napoli Fondazione G. Pascale

MITO 16/MANGO OV2 (a) Phase IV trial Ovarian Ca Stage IIIB-IV (FIGO) ECOG 0-2 Availability of samples for translational res. No Beva contraindications No previous treatments Bevacizumab* 15mg/kg Paclitaxel 175mg/m2 Carboplatin AUC 5 q3wks If not PD Bevacizumab* 15 mg/Kg q 3wks 6 cycles 22 cycles Design *Bevacizumab will be provided by Roche ltd

Aggiornamento 12/2015 L’arruolamento dello studio si è chiuso nel Marzo Eventi (PD+decessi) registrati:185 – 47 decessi – 138 (74.6%) sono PD in assenza di decesso – 163 eventi (88%) antecedenti al 30/06/2015

Maturità Follow-up (Pazienti non decedute) Ultimo aggiornamento al:Pazienti (n=352) Dicembre (1%) Gennaio – Giugno (4%) Luglio – Dicembre (19%) Gennaio-Giugno (32%) Luglio-Settembre (19%) Ottobre – Dicembre (24%)

Maturità Follow-up (Pazienti non PD) Ultimo aggiornamento al:Pazienti (n=214) Dicembre (2.3%) Gennaio – Giugno (6%) Luglio – Dicembre (22.4%) Gennaio-Giugno (33.6%) Luglio-Settembre (16.8%) Ottobre – Dicembre (18.7%) Il 64.3% delle pazienti non ancora progredite ha un follow-up più vecchio di 6 mesi!

MITO 16/MANGO OV2 project: the Phase III trial Ovarian Ca Platinum-sensitive Previous Bevacizumab ECOG 0-2 Availability of samples for translational res. No Beva contraindications R CBDCA AUC5 + PAC 175 mg/m2 q3w or CBDCA AUC4, d1 + GEM 1000mg /m2, d1&8 q3w or CBDCA AUC5+PLD 30mg/m2 q4w CBDCA AUC5 + PAC 175 mg/m2 q3w Plus bevacizumab** 15mg/kg q3w or CBDCA AUC4, d1 + GEM 1000mg /m2, d1&8 q3w Plus bevacizumab** 15mg/kg q3w or CBDCA AUC5+PLD 30mg/m2 q4w Plus bevacizumab** 10mg/kg q2w ARM 1: 6 cycles ARM 2*: 6 cycles *Patients without PD after 6 cycles of combined treatment will receive Bevacizumab maintenance until PD **Bevacizumab will be provided by Roche ltd n=400 pts International (MITO, MANGO, ENGOT)

MITO 16/MANGO OV2 project: the Phase III trial Primary objective: To test whether the addition of bevacizumab to second-line chemotherapy can prolong progression-free survival (PFS) of platinum sensitive ovarian cancer patients progressing or recurring after a first-line treatment including bevacizumab

Statistics primary endpoint: PFS (defined as occurrence of progression or death, whichever comes first). For this analysis PFS as assessed by the local investigator. two-tailed significance level / alpha: 0.05 power 90% median expected PFS in the control arm: 8 months (from the OCEANS study) Hazard ratio to be detected: 0.67 (from the OCEANS study) median expected PFS in the experimental arm: months number of event required for the primary endpoint PFS: 265

Enrollment by Group

Enrollment 204 pts

Clinical Trials Unit Open centres by group and enrollment status

Perché?

Secondary Analyses OS will be measured from the date of randomization to the date of death PFS defined by central independent review ORR will be assessed according to RECIST version 1.1 Identification of prognostic and predictive molecular factors

DICOM FILES flow chart or screen shots new s October 2015 Clinica l Trials Unit For Info: Cristiana de Luca Clinical Trials Unit intnapoli.net full instructions available at Source Date at hand CD Rom Baseline, 3 cycles 6 cycles Compatibility Install / update Java Add usc-intnapoli.net to … VIDEO INSTRUCTIONS ON WEBPAGE “ “ FILE UPLOAD Insert CD, select DICOM folder for upload Upload minutes, if interrupted must restart VIDEO INSTRUCTIONS ON WEBPAGE

Secondary Analyses OS will be measured from the date of randomization to the date of death PFS defined by central independent review ORR will be assessed according to RECIST version 1.1 Identification of prognostic and predictive molecular factors

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