Proton Therapy Trials 'at Risk,' Slow to Enroll Patients

Nick Mulcahy

July 12, 2018

The big question about proton beam radiotherapy — is it any better than conventional radiotherapy? — is being addressed in seven ongoing randomized clinical trials sponsored by the National Cancer Institute (NCI).

But these trials, which cover cancers of the breast, lung, prostate, esophagus, liver, and brain, are all enrolling more slowly than expected, report a trio of experts.

The trials are "at risk" mainly because of this poor accrual, say Justin Bekelman, MD, of the University of Pennsylvania in Philadelphia, and Andrea Denicoff, MS, RN, and Jeffrey Buchsbaum, MD, PhD, both from the NCI.

Unfortunately, "restrictive" insurance coverage is dragging down the entire research effort and is "a principal barrier to enrollment," they write.

Their report was published online July 9 in the Journal of Clinical Oncology.

The trials are essential to compare the efficacy and toxicity of the newer, experimental proton therapy to conventional radiotherapy based on photon therapy, which includes intensity-modulated radiotherapy (IMRT).

However, there are problems with getting patients to receive proton therapy.

"Nearly all commercial insurers and state Medicaid plans do not cover proton therapy for the indications under study," the authors report. Proton therapy has not been proven superior and is more expensive, claim insurers.

The authors talked to physicians, patient advocates, and insurers and reviewed commercial insurers' coverage policies.

On a positive note, the authors found that Medicare "typically does cover the treatment through local coverage determinations, which may include clinical study participation requirements."

Another hopeful sign is that some insurers, including Cigna, Independence Blue Cross, and Blue Cross Blue Shield of Florida, cover proton therapy for selected cancers under study or have established coverage with study participation policies.

In other good news, some proton centers, including those at the University of Pennsylvania, the Mayo Clinic, and the University of Maryland, offer discounts to patients in which the price of proton therapy is equal to that of IMRT. Other centers, such as Northwestern Proton Therapy and Seattle Cancer Alliance, have payment programs in which the center absorbs the treatment cost if proton therapy is not covered upon appeal to an insurer.

These "compromises" from both insurers and proton centers "signal progress," say the report authors, but they are "uncommon." Overall, the situation is at an "impasse."

The result is very slow enrollment. For example, in the breast cancer trial, which involved 893 clinically eligible patients screened through September 2017, 582 patients (65%) had insurance policies that did not cover proton therapy. Bekelman is the principal investigator in this breast cancer trial, and his home institution, the University of Pennsylvania, owns and operates a photon therapy center.

So, as the slate of seven clinical trials drags on, no answers are generated about comparative efficacy and toxicity of the two rival radiotherapy technologies.

"If we can complete the trials in a timely fashion, the results will enable patients to make more informed treatment decisions," said Denicoff in a press statement.

Proton therapy has been aggressively marketed by centers, but, to date, final efficacy results are available for only one randomized clinical trial, in lung cancer. (The lung cancer trial was not among the seven trials in the current study.) In that trial, proton therapy was no better than standard radiotherapy, as reported by Medscape Medical News.

One thing is certain about proton therapy: it costs more. The average Medicare reimbursement per course of treatment, say the report authors, is approximately $10,000 to $20,000 more for proton therapy than for conventional photon-based IMRT, depending on indication.

Three Solutions?

The NCI and the Patient-Centered Outcomes Research Institute (PCORI) have made "major investments to fund" these seven randomized trials, say the report authors. However, those investments evidently did not include paying for patient treatment with the various technologies.

To address this shortcoming, the report authors propose a set of three solutions.

The first emphasizes the need for insurance. The trio says that all stakeholders should come together to establish insurance coverage with a trial participation program for patients who enroll in the NCI- or PCORI-funded randomized radiotherapy treatment trials.

Radiotherapy manufacturers should be a part of the effort and should offer financing, the report authors say.

"It has been noted that linear accelerator and proton therapy manufacturers have not underwritten the costs of treatment during evidence development as drug makers might for new drugs because proton therapy units are considered class II devices by the FDA and approved through the 510(k) program," they observe.

The second solution is to improve enrollment rates and recognize clinicians who are good at enrolling patients.

The third solution is to engage patients more deeply so that they want to enroll.

However, even with patient-friendly trials, enrollment "would be even more fruitful if there was a clear solution to restrictive insurance coverage for proton therapy," say the report authors.

The report was partially funded through a PCORI award and grants from the NCI. The authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online July 9, 2018. Full text

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