Tumor Treating Fields Also Show Efficacy in Ovarian Cancer

Nick Mulcahy

August 07, 2018

Add ovarian cancer to the list of cancers in which tumor treating fields (TTFs), a novel electricity-based therapy, appears to be effective, according to new research.

TTFs are administered with a wearable battery-powered device that delivers alternating electric fields via electrodes attached to the abdominal area. It is marketed as the Optune device (Novocure) and is approved in both the United States and Europe for the treatment of glioblastoma.

TTFs disrupt cell division through physical interactions with key molecules during mitosis in solid tumor cancers, according to the company.

There are ongoing phase 3 studies of the technology in non–small cell lung cancer (NSCLC), locally advanced pancreatic adenocarcinoma, and brain metastasis from NSCLC, in addition to this phase 2 trial in recurrent ovarian cancer.

This single-arm trial, known as INNOVATE, was conducted in 31 patients with recurrent ovarian carcinoma that was resistant to platinum-based chemotherapy. TTF therapy plus weekly paclitaxel provided a median progression-free survival (PFS) of 8.9 months. Seven patients (25%) had a partial response, and 13 patients (46%) had stable disease. Although 61% of patients were alive at 12 months, median overall survival has not yet been reached.

The new data were published online July 27 in Gynecologic Oncology.

"The observed PFS in INNOVATE of 8.9 months is surprisingly high when you take into account the selection of heavily pretreated recurrent ovarian cancer patients," lead author Ignace Vergote, MD, of the Catholic University of Leuven, Belgium, told Medscape Medical News.

Most cases of ovarian cancer (80% to 85%) recur after standard treatment with a platinum-based chemotherapy and thus require additional therapy.

The patients in this trial had undergone a median number of four prior lines of chemotherapy; these include five patients (16%) who had previously received bevacizumab and 30 (97%) who had a taxane such as paclitaxel.

The study authors point out that the 8.9-month PFS in their single-arm trial of TTF therapy plus paclitaxel compares favorably with 3.9-month PFS in historical control patients who underwent weekly treatment with paclitaxel alone. Weekly paclitaxel — often in combination with bevacizumab — is a common option used for such platinum chemotherapy–resistant disease.

The results were deemed sufficiently promising to go ahead with a phase 3 trial, which is now underway, to test TTF therapy in recurrent, platinum chemotherapy–resistant ovarian carcinoma, according to a press statement

These patients need more options. "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," Vergote said in the press statement.

However, the 8.9-month PFS seen in the phase 2 INNOVATE trial of TTF therapy does not compare favorably with results from the AURELIA trial of paclitaxel plus bevacizumab in recurrent, platinum-resistant ovarian cancer, in which median PFS was 10.4 months.

Vergote said that this is not an "apples-to-apples" comparison.

"It should be taken into account that the patients in the AURELIA trial were in second- or third-line therapy, while in the INNOVATE trial, the patients were much more heavily pretreated (ie, had more lines of chemotherapy and more recurrences), and many received already both paclitaxel and bevacizumab," he said.

In the phase 2 trial, which was conducted at four sites in Belgium, Switzerland, and Spain, patients were enrolled from 2014 to 2016. TTF was administered at an intermediate frequency (200 kHz), and paclitaxel was administered weekly for 8 weeks and then on days 1, 8, and 15 of each subsequent 28-day cycle, with a starting dose 80 mg/m2.

Notably, there was less time on treatment with TTF therapy. The mean number of 28-day treatment cycles was 5.5 for paclitaxel and 4.2 for TTF therapy.

Vergote explained that in some patients, TTF treatment was stopped early, because he and his fellow investigators "had to learn how work the device." These patients continued with the standard treatment, paclitaxel.

"TTF is much better tolerated than any chemotherapy," he said.

No serious adverse events related to TTFs were reported. Twenty-six patients (84%) had treatment-related dermatitis, but only one patient permanently discontinued TTF treatment because of the skin rash. Dermatitis was treated with topical steroids.

The median age of the patients was 60 years; 24 patients (77%) had serous histology, 16 patients (52%) had an Eastern Cooperative Oncology Group (ECOG) score of 0, and 15 (48%) had an ECOG score of 1.

Patients were advised to use the TTF device 18 hours a day and to continue for a minimum of 4 weeks after treatment initiation. Median compliance was 77% during the first 3 months of the study, report the investigators.

It is sensible to use TTFs in advanced ovarian cancer because the most common sites of metastatic spread are intra-abdominal, write the study authors. TTFs work as a locoregional therapy.

Patients Like TTF Therapy

In glioblastoma, the only cancer for which TTF treatment is approved, patients have been more receptive to the unusual technology than clinicians, according to experts.

"Patients like it. Doctors have more of a problem. They think it's weird," said Roger Stupp, MD, a neuro-oncologist at Northwestern University in Chicago, Illinois, at the 2017 annual meeting of the Association of Cancer Research. He is a TTF investigator.

At the same meeting, George Demetri, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, acknowledged that TTF is a new modality for treating cancer and thus is "disruptive" and "not easy."

However, another expert said that all TTF phase 3 results need to be looked at with a critical eye because there is no sham TTF treatment. The lack of a double-blinded control group in these studies is a "major scientific limitation," said Stephanie Weiss, MD, a radiation oncologist at Fox Chase Cancer Center in Philadelphia, Pennsylvania, who was asked for comment.

When both physicians and patients know who is receiving an experimental treatment, their behavior may be unconsciously influenced in ways that favor a better outcome, she said.

The INNOVATE study was funded by Novocure. Dr Vergote is an advisor to Novocure and other companies.

Gynecol Oncol. Published online July 27, 2018. Full text

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick

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