Phase I, open-label study of olaparib plus cisplatin in patients with advanced solid tumors.

• DOI: 10.1200/jco.2012.30.15_suppl.1009
• Publication Date: 2020-03-11T15:08:01Z
• Authors: Judith Balmaña; Nadine M. Tung; Steven J. Isakoff; Begoña Graña; Paula D. Ryan; Rezvan Rafi; Michael Tracy; Eric Winer; José Baselga; Judy Ellen Garber
• Keywords: Tolerability; Olaparib; Leukopenia; Discontinuation

1009 Background: Olaparib (AZD2281) is an oral PARP inhibitor active in advanced ovarian and breast cancers. We conducted a multicenter, dose-finding study assessing safety/ tolerability of olaparib capsules plus cisplatin patients (pts) with solid tumors (NCT00782574), for potential use the neoadjuvant setting. Methods: Pts received 21-day(d) cycles olaparib, continuously (Cont) or intermittently (Int), on d1 each cycle.Each cohort recruited ≥3 evaluable pts expansion to ≥6 if ≥1 had dose-limiting toxicity. The last was expanded ensure completed 4 treatment cycles. who 6 combined therapy stopped due cisplatin-related toxicity could enter monotherapy phase (up 400 mg BID olaparib). Primary objective: ≥4 cycles; secondary objectives: pharmacokinetics, antitumor activity. Results: 54 treatment; (n=42), (n=10), pancreatic (n=1) peritoneal cancer. Median number prior regimens = (1–13). C2, C4 C6 enrolled >6 pts. Most common grade (G) 3/4 AEs: neutropenia (n=9; 16.7%), leukopenia (n=4; 7.4%), anemia (n=3; 5.6%), vomiting 5.6%). In C1–C5, 3 AEs leading discontinuation: 1 C2 (thrombocytopenia); 2 C3 (fatigue; complex migraine, dyspnea). C6, all have ended combination no G3/4 hematologic were seen. Overall, 46% dose reduction; 32% AEs. There drug-related deaths. 35 (65%) (C6, n=8). 18/54 (33%) objective response (complete, n=1; partial, n=17); 23 (43%) achieved stable disease. 7 (13%) durable responses year. PK BRCA1/2 data will be presented. Conclusions: Hematologic led reductions + schedule changes 75 mg/m . Tolerability improved 60 Antitumor activity seen during phases, some long responders. [Table: see text]