The ENGOT-ov50/GOG-3029/INNOVATE-3 trial

Emeritus Professor Ignace Vergote from the University of Leuven discusses the findings of the ENGOT-ov50/GOG-3029/INNOVATE-3 trial, which he presented at the ESGO congress.

This phase 3 trial focused on recurrent platinum-resistant ovarian cancer patients and examined the impact of Tumor Treating Fields (TTFields) when combined with paclitaxel. TTFields, an approved treatment modality, have shown significant OS benefits in various challenging cancers such as glioblastoma and mesothelioma. Recent randomized phase 3 trials have also demonstrated positive effects in non-small cell lung cancer. Previous phase 1 and phase 2 studies, along with preclinical research, indicated a synergistic effect between paclitaxel and TTFields in heavily pretreated patients. The main mechanism of action of TTFields, involving the induction of electrical fields to halt cell division, is well understood.

In the ENGOT-ov50/GOG-3029/INNOVATE-3 trial, over 500 heavily pretreated patients, including platinum-resistant patients, were randomized to receive either weekly paclitaxel alone or in combination with TTFields. The primary endpoint of the study was OS, which unfortunately yielded negative results. Given that this is the first study with a negative outcome for TTFields, further investigation was warranted through extensive subgroup analysis.

Interestingly, patients who did not receive prior PLD treatment showed significantly better PFS and OS. Preclinical data showed that doxorubicin induces fibrosis, leading to decreased tissue conductivity, thereby reducing TTFields efficacy. Tumour biopsy analysis will help determine if fibrosis or other factors negatively impacting tissue conductivity are responsible for the diminished efficacy observed in PLD-pretreated patients.

As TTFields are a localized treatment, toxicity is primarily limited to skin irritations, with possible ulcerations in cases of sensitive skin, though these typically resolve quickly.

The negative outcome of the study does not conclude the research on TTFields in ovarian cancer but prompts consideration of how to proceed. Currently, there are no plans for follow-up studies.