Response to Comments: Tumor Treatment Field Therapy (TTFT) - DL34823

Several commenters emphasized that TTFT for the treatment of newly diagnosed GBM should be covered because it is “standard of care” as evidenced by FDA approval and the recommendation by the National Comprehensive Cancer Network’s (NCCN^®) designation of a Category 1 level of evidence.

The final policy extends coverage of TTFT to Medicare beneficiaries with newly diagnosed GBM.

It should be noted that the Food & Drug Administration (FDA) and the Centers for Medicare & Medicaid Services (CMS) are separate agencies with different mandates. While FDA approval is generally necessary for Medicare consideration for coverage of an item or device, it is not sufficient by itself for purposes of Medicare coverage or reimbursement. The FDA is charged with applying the standards of the Federal Food, Drug, and Cosmetic Act, concentrating its review on the safety of a device. Medicare policies, however, focus on whether a device or treatment meets the broader requirement of “reasonable and necessary” as required by §1862(a)(1)(A) of the Social Security Act. 

With respect to the comment concerning the NCCN guidelines, a single source’s guideline is supportive of, but not determinative of, the establishment of “standard of care.” Guidelines present treatment options as recommendations and not mandates for a specific treatment regimen. Moreover, other guidelines have not been uniform in their conclusions regarding TTFT.

The DME MAC Medical Directors received many patient and practitioner comments discussing personal experiences with TTFT used for the treatment of newly diagnosed GBM.

The DME MAC Medical Directors would like to thank the patients, Medicare beneficiaries, and other stakeholders for sharing their stories and experiences. We acknowledge that all were earnestly conveying their personal or loved ones' experiences with TTFT. However, when determining if a treatment is “reasonable and necessary” for purposes of Medicare reimbursement, CMS instructs the DME MACs to rely on publicly available peer-reviewed clinical literature (see CMS Program Integrity Manual, Chapter 13).

Several commenters requested expanding coverage to patients with recurrent GBM.

The original LCD for Tumor Treatment Field Therapy was published in 2014. At that time, the only FDA indication for TTFT was for recurrent GBM. After an evaluation of the literature for recurrent disease, a draft LCD was published by the DME MACs in 2014, and finalized after public comment, with a coverage position that TTFT was not reasonable and necessary. Since there was no approved FDA indication for newly-diagnosed GBM in 2014 when the draft policy was finalized, the original LCD did not distinguish between recurrent and newly diagnosed disease.

In their 2018 reconsideration request, Novocure, the manufacturer of Optune^® and the requestor of this LCD reconsideration, proposed coverage for both recurrent disease and newly diagnosed disease. The CMS Program Integrity Manual Chapter 13 requires the DME MACs to consider reconsiderations valid when “…supported by new evidence, which may materially affect the LCD's content or basis.” [Emphasis added]

Novocure did not submit any new clinical evidence to support their request to extend coverage to recurrent disease, and thus, the reconsideration request for recurrent disease was deemed invalid. The final LCD that will go into effect on September 1, 2019, distinguishes between recurrent GBM, newly diagnosed GBM, and TTFT for other uses.

Several commenters stated the requirement that patients must have maximal debulking surgery is too restrictive and asked this requirement be removed. One commenter specifically requested we allow coverage for patients who have undergone biopsy only.

The FDA-approved indication for TTFT in newly diagnosed, supratentorial GBM includes maximal debulking surgery. A systematic review that examined the association between the extent of tumor resection with survival in newly diagnosed, supratentorial GBM concluded that gross total resection substantially improves overall and progression-free survival, which supports the criteria requiring maximal debulking surgery. However, the DME MACs recognize that not all patients can undergo maximal debulking surgery; therefore, the final LCD language reflects maximal debulking of the tumor when feasible.

Several commenters asked that the criterion, requiring initiation of TTFT within 7 weeks of the end of chemoradiation therapy, be eliminated from the criteria or the timeframe for initiation of TTFT be extended.

The commenters did not provide any clinical evidence to support this position. The final LCD is based on the best currently available clinical literature.

Many commenters asked for the elimination of the requirement that care be received at an NCI-designated facility, expressing concerns such as interrupting established care relationships and travel hardship.

The DME MAC Medical Directors have eliminated this requirement from the final LCD. We continue to encourage Medicare beneficiaries (as do other clinical organizations such as NCCN) to enroll in clinical trials (when eligible), since the treatment options for this cancer continue to rapidly evolve.

Several commenters requested removal of the criterion requiring no evidence of progression of GBM as defined by Response Assessment in Neuro-Oncology (RANO) criteria. Some commenters also noted that pseudo-progression may disqualify beneficiaries for coverage because of the appearance of progression.

Use of RANO criteria addresses the problem of pseudo-progression, a recognized weakness of other criteria such as the MacDonald criteria. According to the RANO criteria, true tumor progression following radiochemotherapy is diagnosed only if there is obvious tumor seen outside the radiation field or by clear histopathologic documentation of progression. Consequently, the use of the RANO criteria, rather than disqualifying beneficiaries, reduces the risk of beneficiaries being denied coverage due to pseudo-progression.

Several commenters asked that the criterion, specifying patients must have a Karnofsky Performance Score (KPS) of at least 70, be lowered or eliminated. One commenter suggested the use of other measures of functionality including Eastern Cooperative Oncology Group (ECOG) scores.

Published clinical evidence does not support the effectiveness of TTFT in newly diagnosed GBM patients with a KPS of less than 70. While other methods of assessing performance status such as ECOG criteria exist, they have not been validated as a predictor of success in the treatment of newly diagnosed GBM with TTFT.

Several commenters asked to allow for greater flexibility regarding the 18 hour per day usage requirement. The commenters note this requirement is too strict as beneficiaries may need to limit or interrupt TTFT use to allow skin irritations/wounds to heal, or for certain medical procedures/tests.

The DME MAC Medical Directors agree. The final LCD language for this criterion has been revised to read “The beneficiary will use TTFT for an average of 18 hours per day.” In addition, the final LCD language has been further modified to take into account interruptions in treatment.

Several commenters asked for an extension or elimination of the 60 - 90 day timeframe to demonstrate benefit of TTFT, due to concerns that a clinical benefit may not be measurable within that timeframe.

The final LCD language does not require that clinical benefit be demonstrated by radiographic measures. Clinical benefit is a judgement of the treating practitioner.

Several commenters asked that all coverage criteria be removed and TTFT be covered without restriction.

The final LCD is based on the best publicly available clinical evidence, and will allow for the best possible opportunity of success for Medicare beneficiaries being treated with TTFT for newly diagnosed GBM.

Several commenters were concerned that newly eligible Medicare beneficiaries will be denied coverage for continuation of TTFT because Medicare coverage criteria were not known at the time the treatment was initiated and, therefore, not met.

The Medicare program has long-standing, clearly defined rules regarding beneficiaries entering Medicare Fee-For-Service (FFS), and the final LCD language is reflective of those rules.

One commenter stated that the requirement that temozolamide must be used in conjunction with TTFT is unrealistic.

The DME MAC Medical Directors agree. The DME MAC Medical Directors point to the final LCD language and the use of the general term “chemotherapy,” not specifically temozolamide.

One commenter requested that patients with early GBM progression be given the opportunity to be treated with TTFT on a case-by-case basis.

Local Coverage Determinations (LCDs) do not preclude individual consideration upon appeal.

One commenter disagreed with the DME MACs’ decision to cover TTFT, citing significant evidence gaps surrounding the safety, efficacy, impact on caregivers, and quality of life with TTFT. The commenter stated: “[T]he Proposed Local Coverage Determination will make it impossible for Medicare to deny the requestor future demand for similar coverage for all other kind of malignancies.”

Each request for a new LCD or to revise an existing LCD will be evaluated on its own merits, based on the requirements outlined in the CMS Program Integrity Manual, Chapter 13.

One commenter stated: “Patients need to know that the claimed benefits were observed in a single clinical trial with questionable scientific validity,” raising doubts over the reported outcomes of the EF-14 study. The commenter noted that the TTFT-treated patients received additional specialist support from Novocure, which could have confounded the results and called for a controlled, independent study of TTFT.

The discussion regarding risks, benefits and costs of any treatment option is best left to the treating practitioner and the patient.

One commenter expressed concern that the primary publications regarding the effectiveness of TTFT were discounted because of significant conflicts of interest, as these studies were industry-sponsored.

All currently available evidence was fully considered in the development of the final LCD.

One commenter noted that the supplier will need to have evidence of compliance with TTFT at the time of bill submission which will cause “a heavy and unreasonable burden on glioblastoma patients to visit their physicians within very specific windows to match their monthly billing cycles.”

It is important that beneficiaries receive appropriate clinical follow-up with their treating practitioner after the initiation of TTFT for newly diagnosed GBM to assess for benefit and adherence, a predictor of TTFT success. The continued coverage language and timeframe is consistent with several other well-established DME MAC LCDs and is required for the DME MACs to support continued reimbursement of the equipment beyond the initial coverage period.

Two commenters sought clarification as to why the DME MACs did not use the existing CAC structure when reconsidering this LCD. One commenter also asked that for future coverage decisions where a CAC is required, the DME MACs use the existing CAC members from all 50 states in lieu of creating an ad hoc CAC committee.

There is no requirement for the DME MAC contractors to utilize the existing Medicare A/B MAC CAC structure. The DME MACs are required to coordinate and publish identical LCDs; therefore, the DME MACs constituted a national, specialty-focused CAC. This specialty-focused CAC was comprised of experts in the fields of neuro-oncology, neurosurgery and oncology.

Two commenters sought clarification regarding the delays in the reconsideration process for TTFT, citing contractor instructions in CMS manuals that suggest that the contractors “…have the discretion to revise or retire their LCDs at any time on their own initiative.”

While the DME MAC contractors do have the discretion to revise or retire a LCD on their own initiative, the DME MACs must still follow the process for revision outlined in the CMS Program Integrity Manual, Chapter 13. The delay in the response to Novocure’s reconsideration request was the result of the CMS transition to new LCD development instructions to implement the 21^st Century Cures Act.

One commenter expressed concern about differences between the proposed Medicare and private insurance coverage of TTFT because “. . . the vast majority of all private healthcare payers provide coverage for Tumor Treating Fields therapy for glioblastoma.”

Coverage determinations by commercial payers and other non-Medicare entities are informative, but not determinative, for the purposes of Medicare reimbursement.

One commenter noted that the requirements for clinical documentation every 60 to 90 days should be removed entirely and replaced with a more straightforward documentation requirement.

The final LCD language does not require that new clinical documentation be obtained every 60-90 days. The continued coverage requirement in the final LCD is a one-time requirement for continued coverage beyond the initial three months of therapy. For Medicare continued medical need documentation, refer to the Standard Documentation Requirements Policy Article (A55426) in the Medicare Coverage Database.

Two commenters stated that the LCD indicates coverage will end at the time of disease progression and requested this restriction be removed.

The only requirement in the final LCD which specifies no evidence of progression is in the initial coverage criteria.

One commenter stated that the TTFT LCD has not kept pace with clinical and scientific developments and the Medicare Administrative Law Judges (ALJs) have indicated there is “overwhelming evidence that TTFT is medically reasonable and necessary.”

The Social Security Act Title XVIII does not precisely define which items or services are "reasonable and necessary." Reasonable and necessary determinations rest with the Secretary. The Act does not contemplate a role for ALJs to broadly determine on a policy-wide level, the reasonable and necessary provisions that are included in a LCD.

One commenter noted that the DME MACs explicitly directed the CAC to only consider evidence for newly diagnosed GBM but the DME MACs issued a policy which precludes coverage of any other application of TTFT including recurrent GBM and other FDA-approved indications (e.g. mesothelioma).

Please review the response to Comment number 3 above.

With respect to coverage of TTFT for mesothelioma, the DME MAC Medical Directors will entertain a reconsideration of the TTFT LCD once the DME MACs receive a request that meets the requirements for a valid reconsideration outlined in the CMS Program Integrity Manual, Chapter 13.