Abstract CT135: INNOVATE: a phase II study of TTFields (200 kHz) concomitant with weekly paclitaxel for recurrent ovarian carcinoma

Abstract

Abstract Background TTFields are a non-invasive, regional antimitotic treatment modality, which have been approved for the treatment of recurrent and newly diagnosed glioblastoma by the FDA. TTFields act by delivering intermediate frequency alternating electric fields to the tumor, and act predominantly by disrupting the formation of the mitotic spindle during metaphase and by dielectrophoretic dislocation of intracellular constituents during cytokinesis. The combination of TTFields and taxanes has demonstrated synergy in preclinical models. In vivo, TTFields led to a significant reduction in tumor volumes in a murine model of ovarian cancer. INNOVATE was the first trial testing TTFields (200kHz) in ovarian cancer patients. Methods Thirty-one recurrent platinum-resistant ovarian cancer patients were enrolled in the INNOVATE trial and treated with TTFields in combination with weekly paclitaxel. All patients had unresectable tumors, an ECOG performance score of 0-1 and measurable disease per RECIST criteria. Patients were required to be at least 4 weeks from surgery and patients with implanted electronic devices were excluded. The primary endpoint was the incidence and severity of treatment emergent adverse events. Secondary endpoints included progression free-survival, overall survival and radiological response rate. Evaluation was performed according to the RECIST 1.1 criteria every 8 weeks Results The median age was 60 (range – 45-77) and most patients (77%) had serous histology. 52% had an ECOG score of 0. The median number of prior chemotherapy regimens was 4.1 (range 1-11) and median time from diagnosis was 48.1 months. All patients were platinum-resistant (median platinum-free interval was 4 months. 97% of patients received prior taxane-containing regimens, 16% received prior bevacizumab and 58% received prior pegylated-liposomal doxorubicin (PLD). The mean number of treatment cycles was 5.5 for paclitaxel and 4.2 for TTFields. The median compliance of patients with TTFields in the first 3 months was 77%. Ten (32%) patients suffered from serious adverse events during the study, none were related to TTFields. Most patients were reported to have mild-moderate, TTFields-related skin irritation, and only two patients (6.4%) had severe-grade skin irritation. The median PFS was 8.9 months (95% CI 4.7, NA). PFS rate at 6 months was 57%. Of the evaluable tumors, 25% had partial response and another 46.4% stable disease – a clinical benefit of 71.4% (median duration of 6.9 months). The median OS was not reached. Conclusions TTFields concomitant to weekly paclitaxel are tolerable and safe in heavily pre-treated platinum-resistant ovarian cancer ovarian cancer patients, with promising progression-free and overall survival. A phase III trial is planned, testing the efficacy of TTFields combined with paclitaxel in recurrent ovarian cancer patients. Citation Format: Ignace Vergote, Roger von Moos, Luis Manso, Cristina Sessa. INNOVATE: a phase II study of TTFields (200 kHz) concomitant with weekly paclitaxel for recurrent ovarian carcinoma [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 CT135. doi:10.1158/1538-7445.AM2017-CT135