Medical Policy: 06.01.34 

Original Effective Date: November 2014 

Reviewed: October 2017 

Revised: October 2017 

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

The mechanism of action as described by the manufacturer: Tumor treating fields (TTF)/Electric tumor treatment fields (ETTF) or TTFields therapy is a locally or regionally delivered treatment that produces electric fields within the human body to disrupt the rapid cell division exhibited by cancer cells. TTFields therapy works by creating alternating, “wave-like” electric fields that travel across their region of usage in different directions. Because structures within dividing cells have an electric charge, they interact with these electric fields.

 

To apply TTF therapy, four insulated transducer arrays are placed on the patient’s shaved scalp according to the tumor’s location. The transducer arrays connect to the portable generator, which noninvasively delivers TTF therapy by generating 200 kHz electric fields within the brain in two perpendicular directions (operated sequentially). Novocure presets the exact treatment parameters; no electrical output adjustments are available to the patient. The patient or caregiver must re-shave the scalp area and replace transducer arrays once or twice a week (every four to seven days) and learn how to change and recharge depleted batteries and connect to an external power supply.

 

The patient can receive TTF therapy outside the hospital on a continuous basis (between 20 to 24 hours per day) for the treatment’s duration, which can be several months.To shower, patients must disconnect the transducer arrays from the generator. The patient can place a shower cap over the existing transducer arrays on the scalp to keep them dry or remove them to shower and replace them with a new pair.

 

The system used for the therapy consists of the Optune Treatment Kit (Novocure, Ltd.) and INE Transducer Arrays. The kit includes the Electric Field Generator (NovoTTF-100A device), power supply, portable battery, battery rack, battery charger, connection cable, and carrying case. The arrays are packaged with a gel layer, padding, medical tape, and overlapping liner. The device is used continuously, so patients carry the six-pound portable generator in an over-the-shoulder bag or backpack during daily activities, with transducer arrays placed on their head and connected to the generator.

 

The primary treatment for glioblastoma multiforme is debulking surgery to remove as much of the tumor as possible. At that time, some patients may undergo implantation of the tumor cavity with a carmustine (bis chloroethylnitrosourea [BCNU]) - impregnated wafer. Depending on the patient’s physical condition, adjuvant radiation therapy, chemotherapy (typically temozolomide), or a combination of the 2 are sometimes given. After adjuvant therapy, some patients may undergo maintenance therapy with temozolomide. In patients with disease that recurs after these initial therapies, additional debulking surgery may be used if recurrence is localized. Treatment options for recurrent disease include various forms of systemic medications such as bevacizumab, bevacizumab plus chemotherapy (eg, irinotecan, BCNU/chloroethylnitrosourea [CCNU], temozolomide), temozolomide, nitrosourea, PCV (procarbazine, CCNU, vincristine), cyclophosphamide, and platinum-based agents.

 

Electric tumor treating fields technology is also being studied as a treatment for other solid tumors (e.g., melanoma and non-small cell lung cancer).  However, there is a lack of published evidence from randomized controlled trials examining the long-term safety and effectiveness of ETTF as a treatment of tumors.

 

A major limitation of the RCT was the lack of a sham device in the control arm, raising the possibility that differences in supportive care or health-promoting behaviors could have contributed to improved outcomes in the device arm. In addition, quality of life data have not yet been presented. A previous open-label randomized trial of TTFields in 237 patients with recurrent glioblastoma showed no improvement in survival compared with physician’s choice chemotherapy.

 

Practice Guidelines

The National Comprehensive Cancer Network (NCCN)

Clinical Practice Guidelines in Oncology/Central Nervous System Cancers. Version 1.2017. This guideline includes alternating electric field therapy (Optune Treatment Kit) as a treatment option for the recurrent disease pathway (GLIO-4), for local, multiple, or diffuse glioblastoma. According to this guideline, “patients with recurring glioblastoma may also consider alternating electric field therapy” (category 2B). The guideline elaborates by stating that “due to lack of efficacy, not all panelists recommend the treatment.”  The National Comprehensive Cancer Network’s central nervous system tumors guidelines (v.1.2016)2 have updated the recommendation for the treatment of glioblastoma (GBM). For the treatment of patients with GBM with good performance status and either methylated or unmethylated or indeterminate MGMT promotor status, a 2A recommendation was added for a treatment option for standard brain radiotherapy, with concurrent temozolomide and adjuvant temozolomide and alternating electric currents therapy.  Currently the recommendation is within the same algorithm stem as clinical trials, based on consensus and lower-level evidence.

 

European Association of Neuro-Oncology (EANO)

EANO Guideline on the Diagnosis and Treatment of Anaplastic Gliomas and Glioblastoma. 2014. This guideline states: “new approaches of glioma therapy… device based therapies such as tumor-treating fields should only be administered in the context of clinical trials.”

 

European Society of Medical Oncology (ESMO)

High-grade Glioma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. 2014. This guideline states: “Applying alternating electric fields—tumor-treating fields—using a battery powered device connected to electrodes placed on the patient’s scalp—was compared with physicians’ choice of chemotherapy in a randomized trial in recurrent disease. TTF failed to prolong survival compared with second-line chemotherapy [I, A].” This guideline defines Level of Evidence I as “evidence from at least one large randomized, controlled trial of good methodological quality (low potential for bias) or meta-analyses of well-conducted randomized trials without heterogeneity.” This guideline defines Grade of Recommendation A as “strong evidence for efficacy with a substantial clinical benefit, strongly recommended.

 

Some clinical researchers assert that TTF "could be further evaluated in combination with chemotherapy, as a maintenance treatment, or as a salvage therapy if radiotherapy or surgery is not possible." Clinical studies are ongoing to determine the safety and efficacy of TTF therapy as part of combination therapy for treating recurrent GBM. TTF therapy is under investigation as a combination therapy with chemotherapy plus bevacizumab and as a combination therapy with chemotherapy after irradiation therapy for treating recurrent GBM.

 

Prior Approval:

Not applicable.

 

Policy:

The use of electrical tumor treatment fields (TTF) is considered investigational for all indications including, but not limited to, treatment of glioblastoma multiforme, and the reoccurrence of glioblastoma multiforme, due to a lack of evidence demonstrating an impact on improved health outcomes, including but not limited to disease survival. This includes in combination with chemotherapy or as stand-alone therapy.

 

The use of tumor treatment fields for all other cancers including, but not limited to non-small cell lung cancer, advanced pancreatic adenocarcinoma (together with gemcitabine), recurrent ovarian cancer,recurrent atypical anaplastic meningioma, and malignant mesothelioma. is considered investigational.

 

Data is limited regarding the effectiveness of electric tumor treatment fields (TTF) for the treatment of recurrent glioblastoma or any indication. Evidence in the published, peer-reviewed scientific literature consists of several small case studies and a single randomized controlled trial (RCT).  Results from the RCT did not demonstrate improved progression free survival or overall survival with this intervention compared with chemotherapy.  In addition, differences in response rates, progression-free survival at 6 months, and reduction in risk of death were not statistically significant.

 

Procedure Codes and Billing Guidelines:

  • To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • E0766: Electrical stimulation device, used for cancer treatment, includes all accessories, any type
  • A4555: Electrode/transducer for use with electrical stimulation device, used for cancer treatment, replacement only

 

Selected References:

  • National Cancer Institute (NCI). Adult Brain Tumors Treatment 2013; 
  • National Comprehensive Cancer Network NCCN Clinical Practice Guidelines in Oncology: Central Nervous System Cancers V1.2015. 
  • Stupp R, Wong ET, Kanner AA, et al. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. Sep 2012;48(14):2192- 2202. PMID 22608262
  • U.S. Food and Drug Administration (FDA) Tumor treatment fields. NovoTTF-10A System. Summary of safety and effectiveness data (SSED). Premarket Approval Application (PMA) No. P100034 2011; Accessed June, 2014.
  • Wong ET, Lok E, Swanson KD, et al. Response assessment of NovoTTF-100A versus best physician's choice chemotherapy in recurrent glioblastoma. Cancer Med. Jun 2014;3(3):592-602. PMID 24574359
  • Ram Z, Gutin PH. Subgroup and quality of life analyses of the phase III clinical trial of NovoTTF-100A versus best standard chemotherapy for recurrent glioblastoma. Neuro-Oncology. 2010;12:iv48-iv49. PMID
  • Ram Z, Wong ET, Gutin PH. Comparing the effect of novottf to bevacizumab in recurrent GBM: A post-HOC sub-analysis of the phase III trial data. Neuro-Oncology. 2011;13
  • Salzberg M, Kirson E, Palti Y, et al. A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors. Onkologie. Jul 2008;31(7):362-365. PMID 18596382
  • Rulseh AM, Keller J, Klener J, et al. Long-term survival of patients suffering from glioblastoma multiforme treated with tumor-treating fields. World J Surg Oncol. 2012;10:220. PMID 23095807
  • Turner SG, Gergel T, Wu H, et al. The effect of field strength on glioblastoma multiforme response in patients treated with the NovoTTF-100A system. World J Surg Oncol. 2014;12(1):162. PMID 24884522
  • Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chi. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202.
  • Stupp R, Kanner A, Engelhard H, Heidecke V, Taillibert S, Lieberman FS, Dbaly V, Kirson ED, Palti Y, Gutin PH. A prospective, randomized, open-label, phase III clinical trial of NovoTTF-100A versus best standard of care chemotherapy in patients with recurrent glioblastoma. J Clin Oncol 2010 Jun 20;28(18 Suppl 1):LBA2007.
  • ECRI Emerging Technology Report. Tumor treating fields therapy (NovoTTF-100A) for recurrent glioblastoma, 01/15/2014.
  • NovoCure Ltd. Sponsor executive summary: P100034. Novocure Ltd. NOVOTTF-100A system for the treatment of recurrent glioblastoma multiforme (GBM) Rockville (MD): U.S. Food and Drug Administration (FDA) 2011 Mar 17. 122 p.
  • Kanner AA, Wong ET, Villano JL, et al. Post Hoc analyses of intention-to-treat population in phase III comparison of NovoTTF-100A system versus best physician's choice chemotherapy. Semin Oncol. Oct 2014;41 Suppl 6:S25-34.
  • Mrugala MM, Engelhard HH, Dinh Tran D, et al. Clinical practice experience with NovoTTF-100A system for glioblastoma: The Patient Registry Dataset (PRiDe). Semin Oncol. Oct 2014;41 Suppl 6:S4-S13.
  • ECRI ECRI Emerging Technology Report. Tumor treating fields therapy (Optune) for recurrent glioblastoma, 09/25/2015.
  • FDA approves drug for treatment of aggressive brain cancer FDA news release Silver Spring (MD): U.S. Food and Drug Administration (FDA); 2009 May 8 [accessed 2015 May 22]. [2 p].
  • Stupp R, Brada M, van den Bent MJ, Tonn JC, Pentheroudakis G, ESMO Guidelines Working Group. High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis treatment and follow-up. Ann Oncol. 2014 Sep;25 Suppl 3:iii93-101. PMID: 24782454
  • Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, Cohen-Jonathan-Moyal E, Frappaz D, Henriksson R, Balana C, Chinot O, Ram Z, Reifenberger G, Soffietti R, Wick W, European Association for Neuro-Oncology (EANO) Task Force on Malignant Glioma. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 2014 Aug;15(9):e395-403. PMID: 25079102
  • Pharma FW. FDA Grants Priority Review Status for Novocure's PMA Supplement Application of Optune in Newly Diagnosed Glioblasoma 2015;
  • Stupp R, Taillibert S, Kanner AA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. Dec 15 2015;314(23):2535-2543. PMID 26670971
  • Wong ET, Lok E, Swanson KD. Clinical benefit in recurrent glioblastoma from adjuvant NovoTTF-100A and TCCC after temozolomide and bevacizumab failure: A preliminary observation. Cancer Med. 2015;4(3):383-391.
  • Food and Drug Administration. FDA approves expanded indication for medical device to treat a form of brain cancer October 5, 2015. FDA: Silver Spring, MD.
  • McNamara MG, Sahebjam S, Mason WP. Emerging biomarkers in glioblastoma Cancers. 2013;5(3):1103-19. PMID: 24202336.
  • ECRI Institute, Technology Evidence Report. Technology Report Update 7/20/2016
  • NovoCure Ltd. Effect of novoTTF-100A in non-small cell lung cancer (NSCLC) patients with 1-3 brain metastases following stereotactic radio-surgery (SRS). In: ClinicalTrials.gov [database online]. Bethesda (MD): National Library of Medicine (U.S.); 2000- [accessed 2013 Apr 03]. [4 p].
  • Novocure Ltd. Novocure announces the completion of enrollment of its PANOVA trial of tumor treating fields plus gemcitabine for treatment of pancreatic cancer. St. Helier (Jersey): Novocure Ltd.; 2015 Jan 12. 2 p.
  • Novocure Ltd. Novocure enrolls first patient in a pilot study of tumor treating fields (TTFields) together with paclitaxel for the treatment of recurrent ovarian cancer. St. Helier (Jersey): Novocure Ltd.; 2014 Oct 30. 2 p.

 

Policy History:

  • October 2017 - Annual review, Policy revised
  • October 2016 - Annual review, Policy revised
  • October 2015 - Annual review, Policy revised
  • November 2014 - New policy

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.