Optune/Temozolomide New Standard of Care for GBM

Median OS was 20.8 months in the Optune arm (95% CI, 19.0-22.6) and 16.0 months in the temozolomide-alone arm (95% CI, 13.9-18.2). The hazard ratio of 0.65 (95% CI, 0.54-0.79;P= .0006) favored the Optune arm. Median progression-free survival (PFS) was 6.7 months in the Optune arm (95% CI, 6.1-8.1) and 4.0 months in the temozolomide arm (95% CI, 3.8-4.3). The hazard ratio for PFS of 0.63 (95% CI, 0.52-0.76;P= .00005) again favored the Optune arm.

“[Optune] should be considered the new standard of care,” lead study author Roger Stupp, MD, of the University of Zurich Switzerland, said when presenting the findings. “The magnitude of benefit is similar to what we saw when we added temozolomide as standard of care.”

Optune is a portable, noninvasive, battery-operated device that attaches directly to the patient’s head to deliver tumor-treating fields to the brain. The device is thought to slow or reverse tumor growth by inhibiting mitosis during metaphase, anaphase, and telophase. The updated findings confirmed the survival benefit observed at the study’s interim analysis, which led to the October 2015 FDA approval of the Optune combination for use in patients with newly diagnosed GBM following surgery, chemotherapy, and radiation therapy.

The phase III EF-14 study randomized 695 patients after they had already received standard temozolomide and radiation therapy (about 4 months after initial diagnosis). A total of 466 patients were randomized to receive Optune and temozolomide and 229 received temozolomide alone.

The 2 treatment arms were well balanced. Among patients with available tissue, over 80% had theMGMTmutation and over 50% had theIDH1mutation.

The patients in the Optune arm received a median of 8.2 cycles of treatment, where a cycle was 1 month, and a median of 6 cycles of temozolomide. Adherence to Optune was 75%. The patients in the temozolomide-alone arm received a median of 5 cycles.

The 2-year OS was 42.5% in the Optune arm (95% CI, 38.0-47.4) and 30% in the temozolomide arm (95% CI, 24.4-37.0). From diagnosis, patient survival was 24.5 months in the Optune arm (95% CI, 22.8-26.3) and 19.8 months in the temozolomide arm (95% CI, 17.6-22.1). From diagnosis, median PFS was 11.2 months (95% CI, 10.0-11.8) in the Optune arm and 7.8 months (95% CI, 7.3-8.2) in the temozolomide arm.

“The 2-year annual survival rate is meaningful, and [Optune] resulted in a 30% absolute increase in survival. We are getting to something that is at least meaningful to patients and their families in terms of longer time to be together,” said Stupp. Further, survival benefit in terms of annual survival rates occurred at 1 year (72.6% in Optune arm vs 65.3% in temozolomide arm;P= .029), at 2 years (42.5% vs 30.0%;P= .001), at 3 years (23.5% vs 15.9%;P= .021), and at 4 years (17.3% vs 10.4%;P= .028).

Cox proportional hazard ratios for OS foundMGMTstatus was the strongest predictor for benefit (HR = 0.512;P<.001). Hazard ratios favored TTF across treatment, gender,MGMTstatus, age, Karnofsky performance status (KPS), and tumor location. Likewise, subgroup analyses indicated benefits for all subgroups. The subgroups analyzed includedMGMTmethylated vs unmethylated; resection by biopsy, partial, or gross total; age under 50 years or 50 years or older; KPS 90-100 or 80 or below; and gender.

In both study arms, 9% of patients experienced grade 3 blood and lymphatic system disorders, while grade 4 disorders were experienced by 4% in the Optune arm and by 2% in the temozolomide alone arm. Convulsions of grade 3 affected 3% of patients in both arms, with 1% of the patients in the Optune arm affected by grade 4 convulsions. In the Optune arm, about half the patients experienced some skin reaction from the treatment device.

Stupp R, Idbaih A, Steinberg DM, et al. Prospective, multi-center phase III trial of tumor treating fields together with temozolomide compared to temozolomide alone in patients with newly diagnosed glioblastoma. Presented at 2016 SNO Annual Meeting; November 17-20, 2016; Scottsdale, Arizona. Abstract LTBK-01.

&ldquo;The long-term analysis further supports our data showing that Optune together with temozolomide is a better treatment option for newly diagnosed GBM patients compared to temozolomide alone,&rdquo; Asaf Danziger, CEO of Novocure, the developer of Optune, said in a statement. &ldquo;We believe these results will give healthcare providers further confidence in our therapy and transform the standard of care in newly diagnosed GBM. Our priority is to improve the lives of GBM patients, and we believe these results will help us to accomplish our mission.&rdquo;