In combination with weekly paclitaxel (Taxol), tumor treating fields (TTF), an antimitotic therapy that delivers continuous low-intensity electrical fields to the tumor region, has been found safe in platinum-resistant ovarian cancer, according to results of INNOVATE (NCT02244502), a phase II single-arm trial.1
With a primary endpoint of safety, INNOVATE found no serious adverse events (AEs) from TTF, and investigators said the combination with weekly paclitaxel was well tolerated with encouraging response and survival data.
Based on these results, investigators will move forward with INNOVATE-3, a prospective open-label study that will randomize 540 patients with recurrent, platinum-resistant ovarian cancer to weekly paclitaxel alone or weekly paclitaxel in combination with TTF tuned to 200 kHz until progression.2
Trial eligibility in INNOVATE was based on histologically-confirmed recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. A total of 31 patients were enrolled, median age of 60 years, and 77% (n = 24) had serous histology and stage III disease. All patients had been previously treated with platinum-based chemotherapy, and a majority had also been treated with taxanes (97%), as well as pegylated liposomal doxorubicin (PLD) (58%).
TTF was delivered at 200 kHz in conjunction with paclitaxel administered weekly for 8 weeks and then on days 1, 8, 16 of each subsequent 28 day-cycle, with a starting dose of 80 mg/m2
Dermatologic AEs, anticipated from use of TTF, were reported in 28 (90%) patients. Two patients reported grade 3 dermatitis and 1 of those discontinued treatment as a result. Patients experiencing grade 3-4 AEs on the combination therapy numbered 17 or 55%. The most common grade 3-4 AEs were blood and lymphatic system disorders (9), anemia (4), and neutropenia (3).
Median 1-year survival was 61% (95% CI, 37-78). Clinical benefit was reported in 20 (71%) of patients, with 7 partial responses and 13 patients with stable disease. Median progression-free survival (PFS) was 8.9 months (95% CI, 4.3-not reached), which investigators said compared favorably with results of prior studies in similar patient populations. In a meta-analysis of phase III trials that involved 1640 patients with recurrent ovarian cancer after primary taxane/platinum therapy, investigators found that the median PFS of patients at their fourth relapse was 4.4 months and median overall survival was 6.2 months.1
“The results of these previous studies, though not directly comparable to the phase II, single arm INNOVATE trial, strengthen the rationale for further evaluating the role of TTFields in the management of platinum resistant ovarian cancer,” investigators wrote.
Ovarian cancer, the second most common gynecologic malignancy, has a poor prognosis. Although most patients achieve a complete remission, 80% to 85% of patients will experience recurrence. Most will develop resistance to platinum therapy.
“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,” said lead author Ignace Vergote, chair of the Department of Obstetrics and Gynecology and Gynecologic Oncology at the Catholic University of Leuven, Belgium.3
“These phase II 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.”
TTF has been tested in a variety of tumor types. The National Comprehensive Cancer Network (NCCN) became the first guideline-setting body to endorse the routine frontline use of TTF when it updated its glioblastoma treatment guidelines in March. That followed a 2011 FDA approval of the Optune TTF system for patients with glioblastoma following tumor recurrence. The system now carries an NCCN category 1 recommendation in combination with radiotherapy and temozolomide for patients with glioblastoma who have undergone surgery.
TTF is self-administered and non-invasive. Transducer arrays are connected to a small, portable medical device, then affixed to the abdomen. In the INNOVATE trial, patients were instructed to wear the device 18 hours per day for continuous delivery throughout the treatment period. Investigators noted median compliance at 3 months of 77% (14 h/day on average).
Patients with recurrent ovarian cancer who progress on paclitaxel following platinum-resistant disease are often treated with PLD, which has response rates below 20%. Gemcitabine and topotecan, 2 alternative treatments, have similarly low response rates, and there is limited data on the efficacy of additional treatments.
INNOVATE phase II trial findings were published in the journal Gynecologic Oncology
on July 31.
The design for INNOVATE-3, NovoCure’s phase III trial of its TTF technology in recurrent ovarian cancer, was disclosed in June at the American Society of Clinical Oncology (ASCO) Annual Meeting 2018.
- Vergote I, von Moos R, Manso L, Van Nieuwenhuysen E, Concin N, Sesse C. Tumor treating fields in combination with paclitaxel in recurrent ovarian carcinoma: results of the INNOVATE pilot study [published online July 31, 2018]. Gynecol Oncol. doi: 10.1016/j.ygyno.2018.07.018.
- Novocure to Present INNOVATE-3 Phase 3 Pivotal Trial Design in Recurrent Ovarian Cancer at the American Society of Clinical Oncology Annual Meeting 2018 [press release]. St. Helier, Jersey: NovoCure; June 4, 2018. novocure.com/novocure-to-present-innovate-3-phase-3-pivotal-trial-design-in-recurrent-ovarian-cancer-at-the-american-society-of-clinical-oncology-annual-meeting-2018/. Accessed August 1, 2018.
- Gynecologic Oncology Publishes Results of the INNOVATE Phase 2 Pilot Study Demonstrating Combination of Tumor Treating Fields With Paclitaxel May Improve Survival Of Patients With Recurrent Ovarian Cancer [press release]. St. Helier, Jersey: NovoCure; July 31, 2018. novocure.com/gynecologic-oncology-publishes-results-of-the-innovate-phase-2-pilot-study-demonstrating-combination-of-tumor-treating-fields-with-paclitaxel-may-improve-survival-of-patients-with-recurrent-ovarian-ca/. Accessed August 1, 2018.