Tumor treating fields (200 kHz) with weekly paclitaxel for recurrent ovarian cancer – the INNOVATE studies

Background: Tumor Treating Fields (TTFields) are non-invasive, regional treatment approved for recurrent and newly diagnosed glioblastoma. TTFields deliver intermediate-frequency alternating electric fields to the tumor by disrupting the mitotic spindle formation. The INNOVATE Phase 2 trial [NCT02244502] tested TTFields (200 kHz) in patients ovarian cancer.

Methods: Thirty-one recurrent platinum-resistant ovarian cancer patients were treated with TTFields plus weekly paclitaxel. Patients had unresectable tumors, ECOG performance 0-1, and measurable disease per RECIST. The primary endpoint was incidence and severity of treatment-emergent adverse events. Secondary endpoints included progression free and overall survival and radiological response rate.

Results: Median age was 60 (range: 45-77), 24 patients (77%) had serous histology, 16 patients (52%) had ECOG score of 0 and 15 (48%) had a score of 1, the median number of prior chemotherapy lines was 4 (range: 1-11). All patients had received prior platinum-based chemotherapy and 30 (97%) had received prior taxanes. No serious adverse events related to TTFields were reported. There was no increase in grade 3-4 adverse events compared to single agent weekly paclitaxel. Twenty-six patients (84%) had the expected TTFields-related dermatitis but only one patient permanently discontinued TTFields due to dermatitis. The median PFS was 8.9 months, 7 patients (25%) had partial response and the clinical benefit rate was 71%. The median overall survival was not reached: the one-year survival rate was 61%.

Conclusions: The INNOVATE Phase 2 study demonstrated that TTFields plus weekly paclitaxel are tolerable and safe in heavily pre-treated platinum-resistant ovarian cancer patients. Based on these results, the INNOVATE Phase 3 study [ENGOT-ov50] of TTFields combined with weekly paclitaxel is planned in platinum-resistant ovarian cancer.