O VARIAN C ANCER C LINICAL T RIALS P LANNING M EETING Unanswered Questions in Upfront Therapy IP Therapy Issue Keiichi Fujiwara, MD, PhD Saitama Medical University

IP T HERAPY IN O VARIAN C ANCER Three large scale randomized trials demonstrated survival benefit on IP cisplatin- based chemotherapy. Meta-analysis indicated IP therapy reduced HR of 0.78 comparing with IV chemotherapy. Controversial Issue Toxicity IP Therapy itself Drug-related Efficacy Trial Design

IP T HERAPY IN O VARIAN C ANCER C ONTROVERSIAL I SSUE Toxicity Catheter problems CV Port Catheter is better than IP Port? Use of IP therapy should be avoided in patients underwent left colon resection and anastomosis? Use of paclitaxel compromise the IP catheter? Drug related Cisplatin? IP Paclitaxel?

IP T HERAPY IN O VARIAN C ANCER C ONTROVERSIAL I SSUE Efficacy Trial Design of GOG172

GOG172 T RIAL Epithelial Ovarian Cancer Optimal Stages III Paclitaxel 135 mg/m2/24h IV D1 Cisplatin 75 mg/m2 IV D2 Q21, 6 Cycles Paclitaxel 135 mg/m2/24h IV D1 Cisplatin 100 mg/m2 IP D2 Paclitaxel 60 mg/m2 IP D8 Q21, 6 Cycles Randomization

IP T HERAPY IN O VARIAN C ANCER C ONTROVERSIAL I SSUE Efficacy Trial Design of GOG172 Survival Benefit was obtained because of IP Cisplatin? More Cisplatin Dose? Probably Not IP Paclitaxel? Day 8 Paclitaxel? Role of Targeted Agents with IP Chemotherapy Impact of JGOG3016 Trial

IP C HEMOTHERAPY IN O VARIAN C ANCER Trial Endpoints to be Answered Less Toxic Combination Can Carboplatin be replaceable to Cisplatin? Is Day 8 IP Paclitaxel required? Efficacy Assessment Is IP Carboplatin better than IV Carboplatin? Dose Day 8 IP Paclitaxel matter or Only Day 8 Paclitaxel (IV) matter? New Approach Combination of Targeted Agents Bevacizumab

GCIG T RIAL (P HASE II/III S TUDY ) Neoadjuvant Chemotherapy for Stage III Epithelial Ovarian Cancer Followed by Interval Debulking Surgery Resulting Residual Disease < 1 cm Paclitaxel 175 mg/m2 IV Carboplatin AUC 6 IV Paclitaxel 60 mg/m2 IV D8 Q21, 6-8 Cycles Paclitaxel 175 mg/m2 IV Carboplatin AUC 6 IP Paclitaxel 60 mg/m2 IV D8 Q21, 6-8 Cycles RANDOMZERANDOMZE Paclitaxel 135 mg/m2 IV Cisplatin 75 mg/m2 6 IP Paclitaxel 60 mg/m2 IP D8 Bevacizumab Q21, 6-8 Cycles Pick the winner strategy

P LANNED J APANESE IP T RIAL Epithelial Ovarian Cancer Stages II-IV Excluding Clear Cell Carcinoma Paclitaxel 80 mg/m2 IV Weekly Carboplatin AUC 6 IV Q21, 6-8 Cycles Paclitaxel 80 mg/m2 IV Weekly Carboplatin AUC 6 IP Q21, 6-8 Cycles Randomization Primary Endpoint: PFS Secondary Endpoint: OS, Toxicity, QOL

P LANNED GOG T RIAL Optimal Debulked Stage III Epithelial Ovarian Cancer Paclitaxel 175 mg/m2 IV Carboplatin AUC 6 IV Bevacizumab Q21, 6-8 Cycles Paclitaxel 175 mg/m2 IV Carboplatin AUC 6 IP Bevacizumab Q21, 6-8 Cycles RANDOMZERANDOMZE Paclitaxel 135 mg/m2 IV Cisplatin 75 mg/m2 6 IP Paclitaxel 60 mg/m2 IP D8 Bevacizumab Q21, 6-8 Cycles