Abstract CT131: A randomized (RCT) phase II study of oncolytic reovirus (pelareorep ) plus standard weekly paclitaxel (P) as therapy for metastatic breast cancer (mBC)
Authors: Bernstein Vanessa , Ellard Susan , Dent Susan F. , Gelmon Karen A. , Dhesy-Thind Sukhbinder K. , Mates Mihaela , Salim Muhammed , Panasci Lawrence , Song Xinni , Clemons Mark , Tu Dongsheng , Hagerman Linda J. , Seymour Lesley 
Published: July 2017

Abstract
Background: Pelareorep is a Dearing strain of reovirus serotype 3, with demonstrated in vitro and in vivo activity in many cancers and synergistic cytotoxic activity with microtubule targeting agents, including taxanes. This study was designed to determine the efficacy and safety of pelareorep + P compared to P alone in mBC. Materials and Methods: This randomized, open-label, phase II study enrolled subjects who had mBC previously exposed to chemotherapy (CT). Subjects were randomized 1:1 between Arm A (P 80 mg/m2 day 1, 8 and 15 q 28 days plus pelareorep 3 x 1010 TCID50 day 1,2,8,9,15,16 q 28 days) and Arm B (P 80 mg/m2 day 1, 8 and 15 q 28 days). Treatment was continued until disease progression (PD) or unacceptable toxicity. Objective response was assessed every 8 weeks. Primary endpoint was progression free survival (PFS). The study had 90% power to detect an improvement of PFS from 4 to 7.5 months (HR 0.5, two-sided α=0.2). All p-values are two-sided. Results: Between July 2012 and April 2016, 81 subjects were accrued: 7 to the safety run-in for arm A, 36 to Arm A and 38 to Arm B. All had received prior CT, 59 as adjuvant treatment and 48 for mBC. Patients in Arm A had more favorable prognostic features, including lower LDH and less prior therapy. The median cumulative dose of P was 960 mg/m2 for arm A vs. 828 mg/m2 for arm B. Similar numbers of subjects in both arms required dose reductions, predominantly for myelosuppression. The median duration of treatment was 16.1 weeks for pelareorep and P in arm A and 14.1 weeks for P in arm B. With a median follow-up of 29.5 months, the median PFS was 3.78 mo for arm A and 3.38 mo for arm B (HR 1.04, 80% CI 0.76-1.43, p=0.87). Median OS was 17.4 mo for arm A and 10.4 mo for arm B (HR 0.65, 80% CI 0.46-0.91, p=0.1). Response rates (RR) were 25% for arm A and 23.7% for arm B (p=0.87). Pre-specified subset analysis found statistically significant differences in OS in patients with ECOG 1 or 2, aged &lt; 65 yr, and no prior P treatment. Exploratory analysis of biomarkers found significant differences in OS in patients with wild type PIK3CA, KIT, APC, PTEN, ATM, AKT1, mutated TP53, and both wild type and mutated MET, although the number of pts was small. When grade 3 or higher adverse events (AE) were considered, only the incidence of fatigue was found in ≥10% (16% on Arm A vs 13%, arm B, p=0.76). Hematologic grade 3 or higher effects observed in ≥10% patients included lymphopenia (5% arm A vs 18% arm B, p=0.08), and neutropenia (23% arm A vs 26% arm B; p=0.8). There was a statistically significant difference in grade 3 or higher LDH (0% arm A vs 13% arm B, p=0.03). There were no treatment related deaths. Conclusions: This first, phase II, randomized study of pelareorep + P vs P in mBC previously exposed to CT, did not meet its primary endpoint of PFS. Despite similar PFS and RR there was a statistically significant improvement in OS for pelareorep + P pts. Given these data, further exploration of the role of pelareorep + P in mBC may be of interest.
Citation Format: Vanessa Bernstein, Susan Ellard, Susan F. Dent, Karen A. Gelmon, Sukhbinder K. Dhesy-Thind, Mihaela Mates, Muhammed Salim, Lawrence Panasci, Xinni Song, Mark Clemons, Dongsheng Tu, Linda J. Hagerman, Lesley Seymour. A randomized (RCT) phase II study of oncolytic reovirus (pelareorep ) plus standard weekly paclitaxel (P) as therapy for metastatic breast cancer (mBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT131. doi:10.1158/1538-7445.AM2017-CT131