Final Results Of Nktr-102, A Topoisomerase I Inhibitor-Polymer Conjugate, In Patients (Pts) With Pretreated Metastatic Breast Cancer (Mbc) Demonstrating Significant Antitumor Activity.

269 Background: NKTR-102 is a topoisomerase I inhibitor-polymer conjugate with reduced peak concentration and a continuous concentration profile. Methods: This was an open-label phase II study in MBC pts following PD on a taxane (T). Pts were randomized to NKTR-102 given IV at 145 mg/m2 over 90-min every 14 or 21 days. Efficacy endpoints included ORR by RECIST v1.0; PFS and OS. Results: 70 pts (35 per schedule) randomized from Feb 2009 to May 2010 (median follow-up: 10 mo). Median age: 55 (range 33–83). ECOG PS 0/1: 40%/60%. Neoadjuvant and/or adjuvant: 74%. Median number of prior cytotoxic regimens for metastatic disease: 2. All pts had received prior T: 7% (adjuvant); 93% (metastatic). 89% had received prior anthracyclines (A): 63% (adjuvant); 26% (metastatic). 63% had received prior AT only (23% in MBC); an additional 26% had received prior AT/capecitabine (ATC). 61% were ER/PR+; 30% had TNBC; 86% had visceral metastases. Median PFS for q14d, q21d and overall were 3.5 mo, 5.3 mo and 4.6 mo. Median OS for q14d, q21d and overall were 8.8 mo, 13.1 mo and 10.3 mo. Toxicity was manageable, with diarrhea as the most common grade 3+ toxicity, with median time to onset ∼3 mo. Discontinuation from study drug due to AEs: 20%/14% for q14d/q21d. Neuropathy was absent; alopecia was minimal (20%/11% grade 1–2 for q14d/q21d). Conclusions: NKTR-102 demonstrates significant anti-tumor activity in pts with advanced MBC, including poor prognosis pts with TNBC and having received prior ATC. A phase III study is being planned in patients with MBC previously treated with taxanes. [Table: see text]