Abstract
Introduction/BackgroundTumor Treating Fields (TTFields) have shown efficacy in glioblastoma, non-small-cell lung cancer and pleural mesothelioma, with favorable safety. TTFields’ anti-mitotic effects are dose-dependent and may be affected by tissue conductivity changes. Preclinical data (unpublished) showed doxorubicin induces tumor fibrosis and changes tissue conductivity. This randomized phase 3 study investigated TTFields therapy with paclitaxel (TTFields+PTX) vs paclitaxel (PTX) in patients with platinum-resistant ovarian cancer (PROC).MethodologyENGOT-ov50/GOG-3029/INNOVATE-3 (NCT03940196) enrolled adults with PROC, ≤5 prior lines of therapy (LOT), ≤2 prior LOT following platinum-resistance, and ECOG 0-1. Patients received TTFields (200 kHz; ≥18 hours/day) + PTX (80 mg/m2) weekly or PTX. Primary endpoint was overall survival (OS).Results558 patients were randomized to receive TTFields+PTX (n=280) or PTX (n=278) March 2019 to November 2021. Baseline characteristics were well-balanced (median age, 62 [22-91] years; serous histology, 88.7%; ECOG 0, 60.2%; BRCA+, 15.6%). 24.4% of patients received 4+ prior LOT; 65.9% received prior bevacizumab. In the intention-to-treat population, TTFields therapy median duration was 15.9 (0.1–159.7) weeks. Median OS was 12.2 months with TTFields+PTX versus 11.9 months with PTX (HR, 1.01; 95% CI, 0.83-1.24; p=0.89). Grade ≥3 adverse events (AEs) occurred in 60% of patients with no TTFields-related increase in severe systemic toxicities; 83.6% of patients receiving TTFields had a device-related skin AE (all Grade 1/2). Post-hoc analysis in pegylated liposomal doxorubicin (PLD)-naïve patients showed extended survival with TTFields+PTX (n=113) vs PTX (n=88) (16 vs 11.7 months; HR, 0.67; 95% CI, 0.49–0.94; p=0.03). Multivariate Cox regression analyses to eliminate alternative covariates potentially leading to survival superiority in PLD-naïve patients showed that TTFields and prior PLD status were statistically significant covariates following stepwise narrowing (HR, 0.56; p=0.0006).ConclusionIn the overall cohort TTFields+PTX did not improve OS compared with PTX. Post-hoc analysis of PLD-naïve patients showed clinically and statistically significant survival improvement in patients receiving TTFields therapyDisclosuresMedical writing support was provided by Makaila Wallin, PharmD, of The Curry Rockefeller Group, LLC (Tarrytown, NY), and was funded by Novocure, Inc.