Introduction/Background Tumor Treating Fields (TTFields) provide non-invasive cancer treatment through continuous delivery of alternating electrical fields, administered through arrays on the skin of patients. TTFields have been investigated in combination with weekly paclitaxel for the treatment of recurrent ovarian cancer (OC) (INNOVATE, NCT02244502). This phase 2 study showed good tolerability and promising survival results and provided motivation for the ongoing phase 3 study (INNOVATE-3/ENGOT-ov50/GOG-3029, NCT03940196). Besides the originally hypothesized anti-mitotic mechanism, induction of double-stranded DNA breaks and inhibition of DNA damage repair were reported as a result of TTFields in vitro. Therefore, this study aimed to evaluate combination treatment with TTFields and concomitant poly ADP ribose polymerase (PARP) inhibition (Olaparib) in a high-grade serous OC mouse model.

Methodology C57BL/6 mice (N= 4 or 5) were inoculated with 5x106 ID8-fLuc OC cells intraperitoneally. One week post inoculation, transducer arrays were applied to the shaven skin of the mice and TTFields treatment (200 kHz) was initiated for a period of four weeks. Concomitantly, Olaparib (50mg/kg) was administered through daily oral gavage. Bioluminescent imaging (BLI) analysis was performed before, during and after treatment to observe tumor growth. Mice were analyzed for survival using endpoint criteria described previously.

Results TTFields combined with Olaparib resulted in a survival benefit compared to non-treated, TTFields only treated and Olaparib only treated tumor-bearing mice (median survival 97 vs 76, 74 and 80.5 days respectively). A repeat study showed similar prolongation of the combination treatment compared to TTFields alone (median survival 92 vs 76 days). These results were underscored by BLI analysis showing reduced tumor growth in Olaparib + TTFields treated mice in both experiments.

Conclusion Our experiments provide first in vivo evidence that a combination of TTFields and PARP inhibition can result in a survival benefit in OC. Further research is needed to confirm and expand these findings.

Disclosures AC is a contracted researcher for Oncoinvent AS and Novocure and a consultant for Sotio a.s. and Epics Therapeutics SA.