GBM is a high-grade brain tumour with poor prognosis and no curative treatment. It is the most common primary malignant tumour of the CNS.

There are approximately 1,850 patients with GBM in Canada (data from 2010 to 2017).¹

The current treatment strategy is the Stupp regimen, which includes surgical resection followed by chemoradiation and adjuvant chemotherapy with temozolomide.

GBM is physically, psychosocially, and economically burdensome for patients and their caregivers.

Optune (NovoTTF-200A) is a portable and noninvasive device that treats GBM by providing continuous, locoregional treatment with TTFields.

There have been no new treatment options that improve survival of patients with GBM since the early 2000s.

The current chemotherapeutic drug temozolomide is considerably less effective in patients with MGMT unmethylated tumours,⁴ which constitutes up to 60% of patients with ndGBM.⁵

None of the available treatments (including Optune) are curative and the disease has a poor prognosis.

CADTH reviewed evidence from a multicentre, open-label RCT that compared the efficacy and safety of Optune with temozolomide in adult patients with ndGBM following maximal debulking surgery and completion of RT, together with and after standard of care maintenance chemotherapy.

Optune plus temozolomide likely increases PFS at 6 months of treatment and OS at 24 months of treatment compared to temozolomide alone (moderate to low certainty).

The treatment effect of Optune plus temozolomide on PFS and OS may be dose-dependent, with at least 18 hours of daily Optune use required for the most benefit.

Optune plus temozolomide may result in little to no difference in HRQoL (very low certainty) when compared to temozolomide alone.

CADTH identified weaknesses of the study that could affect the internal validity of the results.

The patient inclusion criteria were skewed toward enrolling patients with a better functional and disease status, and better prognosis at baseline. Only those patients who survived (without progression) from diagnosis to randomization were included in the study.

The open-label design of the trial created uncertainty in interpreting the patient-reported outcomes.

There were concerns regarding the crossover of some patients from the temozolomide-alone arm.

The study participants were slightly younger and had better health status and degree of independent functioning than what is typically observed in clinical practice. These factors lowered the generalizability of the results.

Overall, evidence was of moderate to very low certainty due to concerns regarding selection bias and low generalizability of results to real-world settings.

No longer-term studies or indirect comparisons were identified by the sponsor for the review.​

CADTH found little to no difference in serious adverse events between Optune plus temozolomide and temozolomide alone (moderate certainty).

Optune treatment did not clearly add safety concerns to temozolomide alone.

Patients receiving Optune with temozolomide may benefit from clear MRI results, prolonged survival, and some resumption of daily activities. Nonetheless, they may also experience side effects, particularly scalp irritation and dermatitis.

Most patients with lived experience using Optune recommended making the treatment more accessible to people living with GBM.

The submitted fee for Optune is $27,000 per month, which includes the treatment kit and support features. This cost is added to the cost of temozolomide.

At the submitted monthly fee for Optune and public list price for temozolomide, the ICER for Optune plus temozolomide vs. temozolomide alone was $899,470 per QALY gained (incremental costs = $336,902; incremental QALYs = 0.37). At this ICER, Optune plus temozolomide was not considered cost-effective relative to temozolomide alone at conventional willingness-to-pay thresholds (i.e., $50,000 per QALY gained or $100,000 per QALY gained).

A price reduction of between 91% and 97% is required for Optune plus temozolomide to be considered cost-effective at a willingness-to-pay threshold between $50,000 and $100,000 per QALY gained.

The budget impact of reimbursing Optune through the federal, provincial, and territorial public drug plans (excluding Quebec) is estimated to be $75,795,323 over 3 years.

Optune is estimated to be used by 232 patients over 3 years.

The long-term efficacy of Optune is uncertain and may be dependent on the frequency and duration of the use of Optune by patients.

The sponsor assumed that patients would be functionally cured after 15 years. There is no robust evidence to support the validity of this assumption.

Time on treatment for Optune plus temozolomide and temozolomide alone were based on data from the EF-14 trial. There were wide ranges in time on treatment in the trial and differences in median and mean time on treatment. It is unclear how time on treatment data from the EF-14 trial will translate to Canadian clinical practice.

Health state utility values did not meet face validity.

Following surgical resection and RT with concomitant temozolomide, patients would receive Optune during the adjuvant temozolomide treatment phase.

The sponsor assumed the payer for Optune would be drug plans.

The sponsor assumed that the monthly rental fee would cover repair, replacement, maintenance, technical support, and clinical support.

A clinician must undergo a training course provided by the sponsor and obtain certification to prescribe Optune.

It is suggested that there are no additional costs to the health care payer associated with training physicians, patients, and caregivers to be familiar with the technology.

Clinical experts consulted by CADTH commented that it may be reasonable for patients to continue treatment beyond initial disease progression.

It is unclear whether the CADTH participating drug plans, as suggested by the sponsor, are the appropriate payer for Optune.

It is unclear whether the subscription model and full set of included services indicated by the sponsor will be implementable by the payer.

The lifespan of Optune and its components is uncertain. The responsiveness of the sponsor to deliver the suggested services within the monthly fee cost is unclear. It is also unclear whether any new versions will be associated with changes to the sponsor’s fee structure.

It is unclear whether the same standard of device repair and maintenance support observed in clinical trials could be maintained as the customer base of Optune expands in the real-world health system environment.

Effectiveness of Optune appears to be dependent on treatment adherence (e.g., time wearing the device); thus, patient motivation may be important in determining device uptake. Family and caregiver support may be important in increasing the treatment adherence.

It is unclear whether any suggested discontinuation criteria can be implemented.

The balance of benefits, risks, and burdens associated with Optune is understood within the context of an individual patients’ values and situation. Some patients may consider Optune as providing hope and an opportunity to gain a sense of control over the disease, while others may consider it as burdensome or a visible reminder of the disease.

To mitigate false hope, clinicians will need to covey that burdens experienced with maintenance chemotherapy will not be lifted with the addition of Optune, and instead, patients and caregivers will be required to manage an additional treatment modality.

As patients with ndGBM can be described as “vulnerable,” careful attention must be paid to the quality of consent conversations to support informed decision-making and respect for patient autonomy. Eliciting a patient’s values with respect to treatment is also important as disease progression may impair capacity to consent and require the involvement of a substitute decision-maker.

Consent conversations require ensuring that patients and caregivers understand that Optune is not curative and is proposed as an addition to maintenance chemotherapy, and that Optune is considered within a full range of treatment and care options, including available palliative care supports. Consent should also cover privacy considerations as the use of Optune requires transmitting patient data to the sponsor.

Equity- enhancing strategies will need to be explored if Optune is to be accessible in a fair and effective manner for patients in Canada. Special attention is required to address barriers to accessing Optune due to geography, socioeconomic status, language barriers, requirements for additional caregiver support, and barriers to accessing oral temozolomide in jurisdictions where it is not reimbursed.

Acceptability of the device, and the extent to which Optune meets patients’ needs for effective, accessible, and easily usable treatment remain uncertain and will likely depend on an individual patient’s values and caregiver support network.

Limitations in HRQoL data and the generalizability of the trial findings have implications for consent conversations and the ability to adhere to and benefit from treatment in a diverse patient population in the real-world.

Further study on how, or if, factors such as functional status, race, sex, age, socioeconomic status, and availability of caregiver support have implications for acceptability and ability to adhere to treatment would be helpful to support patient-centred care and equitable access given the diversity of the population in Canada.

There are no data for pregnant patients and neither Optune nor temozolomide are recommended for use in this population. Patient or substitute decision-maker preferences may prompt reconsideration as risk tolerance and individual circumstances vary.