Optune plus temozolomide extended survival in glioblastoma

Issue: December 10, 2015

Use of the noninvasive regional therapy Optune with temozolomide chemotherapy significantly extended OS and PFS in patients with newly diagnosed glioblastoma, according to interim phase 3 study results presented at the Annual Meeting of the Society for Neuro-Oncology.

Perspective from Jeffrey Raizer, MD

Optune (Novocure) creates Tumor Treating Fields, or low-amplitude alternating electric fields (100 kHz to 300 kHz), that travel across the upper portion of the brain in various directions. The electric fields, delivered through four transducer arrays played on the patient’s scalp, are intended to prevent glioblastoma cancer cells from dividing.

Roger Stupp, MD, director of the University Hospital Cancer Center at the University of Zurich in Switzerland, and colleagues sought to evaluate the addition of therapy with Optune to standard-of-care temozolomide (Temodar, Merck) chemotherapy.

The interim analysis included data from 315 patients with newly diagnosed glioblastoma. All patients received radiation therapy concomitantly with temozolomide.

Researchers then assigned 210 patients (median age, 57 years) to Optune plus adjuvant temozolomide. The other 105 patients (median age, 58 years) received adjuvant temozolomide alone.

Patients in the experimental arm received a median six (range, 1-25) cycles of adjuvant temozolomide, and patients in the control arm received a median four (range, 1-24) cycles of temozolomide. Patients in the experimental arm received eight cycles of Optune therapy.

Minimum follow-up was 18 months (range, 18-60).

Median PFS was 7.1 months (95% CI, 5.9-8.2) among patients assigned Optune therapy plus temozolomide vs. 4 months (95% CI, 3-4.3) among those assigned temozolomide alone (HR=0.63; P=.001).

Median OS also was significantly extended in the Optune arm (19.6 months vs. 16.6 months; HR=0.75; P=.034).

Researchers reported 2-year OS rates of 43% (95% CI, 36-50) among those assigned Optune therapy and 29% (95% CI, 21-39) among those assigned temozolomide alone.

Skin irritation occurred in 45% of patients treated with Optune. Two percent of patients developed grade 3 or grade 4 skin irritation.

Severe seizure occurred in 7% of patients in both study arms.

Based on these results, the independent monitoring committee recommended the trial stop early, and patients in the control arm were able to cross over to the Optune arm.

“These results are spectacular,” Stupp said in a press release. “A new standard of care for patients suffering from glioblastoma is born.”

For more information:

Stupp R. Abstract #NT-40. Presented at: Annual Meeting of the Society for Neuro-Oncology; Nov. 13-16, 2014; Miami, Fla.

Disclosure: Stupp reports travel expenses from and an uncompensated advisory role with Novocure.

Perspective

Jeffrey Raizer, MD

Practice-changing trials in neuro-oncology are few but, for the second time in a decade, Stupp and colleagues have again presented the results of a trial that could change how patients with newly diagnosed glioblastoma are treated. The data from the EF-14 trial were presented at the annual meeting of the Society of Neuro-Oncology in Miami in November 2014. This randomized trial compared radiation and temozolomide with radiation, temozolomide and NovoTTF-110A (now called Optune) in newly diagnosed glioblastoma. The results were much awaited, as many in the field were skeptical about the effectiveness of the device.

The device creates “tumor treating fields” that, in essence, act like anti-mitotic chemotherapeutic agents.

After the completion of radiation therapy and temozolomide, patients were randomly assigned to either adjuvant temozolomide alone or with NovoTTF for 2 years or until progression, with an option of continuing the device beyond first progression. The primary endpoint was PFS, with an interim analysis when 315 patients had at least 18 months of follow-up. Arms were well balanced for age, Karnofsky performance score, extent of resection and O⁶-methylguanine-DNA methyltransferase (MGMT) status.

In the intention-to-treat population, PFS was 7.1 months in the experimental group and 4 months in the control arm. OS was 19.6 months in the experimental arm vs. 16.6 months in the control arm, equating to an HR of 0.75. The FDA has now allowed patients on the control arm to cross over to the device.

This trial shows the effectiveness of Novo-TTF in patients with newly diagnosed glioblastoma. Still, many questions remain that likely will be answered as the data continue to mature. Some of these are: (1) Which patients benefit the most, younger vs. older, or MGMT methylated vs. unmethylated? 2) Does the device need to be worn every day or can “device holidays” occur, increasing the time off the device without leading to a decline if efficacy? 3) Which patients are optimal candidates for device use, or which ones will embrace Novo-TTF? Time hopefully will answer these questions, and many others, and allow for personalized care with Novo-TTF.

Jeffrey Raizer, MD

Northwestern University Feinberg School of Medicine

Disclosures: Raizer reports no relevant financial disclosures.