Adding Tumor Treating Fields (TTFields) — a therapy that uses electric fields to induce cell death — to weekly Taxol (paclitaxel) more than doubles the time to disease worsening or death in ovarian cancer patients who failed at least one prior therapy, a Phase 2 clinical trial shows.
Compared to historical control participants, who live without disease progression for only 3.9 months when receiving Taxol alone, patients in this trial had no signs of disease worsening or death for a median of 8.9 months.
The study, “Tumor Treating Fields in combination with paclitaxel in recurrent ovarian carcinoma: Results of the INNOVATE pilot study,” was published in the journal Gynecologic Oncology.
Treatment of choice for ovarian cancer patients usually is a chemotherapy regimen containing a platinum agent, like cisplatin or carboplatin. However, while most patients respond, the majority will see their cancer return or progress within a few months.
These patients — platinum-resistant ovarian cancer patients — have numerous therapies available, but survival rates are still low.
“A clear unmet need remains for patients with recurrent ovarian cancer, particularly for those patients resistant to platinum-based chemotherapy, with median overall survival of about 13 months post recurrence,”Ignace Vergote, an investigator in the trial, said in a press release. Vergote is chairman of the Department of Obstetrics and Gynaecology and Gynaecologic Oncology at the Catholic University of Leuven, European Union.
Taxol leads to high response rates in platinum-resistant patients, and studies in lab-grown cells and mice have shown that TTFields works in synergy with this medicine, increasing cancer cell death.
So, NovoCure, the company developing the TTFields technology, designed a Phase 2 trial to determine if a combination of TTFields and weekly Taxol was safe and delayed disease progression or death in ovarian cancer patients who had received at least one prior line of therapy and who had failed to respond to a platinum-based chemotherapy.
TTFields disrupts cancer cell division by delivering intermediate frequency alternating electric fields and activating cells’ “suicide” programs.
For ovarian cancer patients, the therapy is delivered by four electrodes placed on a woman’s torso in the region surrounding the tumor. The delivery system is portable and allows patients to maintain a regular daily routine.
The trial, called INNOVATE (NCT02244502), enrolled 31 patients. In addition to safety and progression-free survival, researchers also assessed overall survival and response rates.
Because all patients in the trial received the combination, researchers compared their results with those of control patients from other studies who were treated with weekly Taxol only.
Patients lived for a median of 8.9 months without any signs of disease progression, a figure that more than doubled that seen in control patients (3.9 months). Also, 61% of patients taking the combination survived one year or more after the treatment.
Partial responses were seen in 25% of patients, and an additional 46% achieved disease stabilization after the treatment, reaching a clinical benefit rate of 71%.
Importantly, most patients (77%) complied with the therapy for the first three months of treatment.
Regarding safety, researchers found two cases of severe skin irritation and other side effects mainly affecting the blood, gastrointestinal, and respiratory systems. However, the number of severe or life-threatening side events was similar to that seen in patients receiving Taxol alone.
“These Phase 2 pilot data show that Tumor Treating Fields combined with paclitaxel has the potential to increase survival without significantly increasing side effects for recurrent ovarian cancer patients,” Vergote said.
Eilon Kirson, MD, and Novocure’s chief science officer and head of research and development, commented: “These are encouraging results in a disease state that is very difficult to treat. We are now working to open INNOVATE-3, a Phase 3 pivotal trial to further study Tumor Treating Fields for the treatment of recurrent ovarian cancer.”
The company announced the INNOVATE-3 Phase 3 trial in May 2018.