New cancer drugs lead to life-threatening financial choices
Hutch researchers in HICOR take on one of cancer treatment’s deadliest side effects, financial toxicity; call for Medicare policy change
A raft of studies by health outcomes researchers at Fred Hutchinson Cancer Research Center illustrate the difficult choices cancer patients are forced to make regarding an expanding class of targeted drugs called tyrosine kinase inhibitors, or TKIs.
The first such drug, Gleevec, was introduced in 2001 and became a game-changer for chronic myelogenous leukemia, or CML, turning a lethal disease into a manageable one. And TKIs have worked incredibly well in some types of non-small cell lung cancer and certain stomach cancers, too.
But these oral medications don’t come cheap, even with insurance. The out-of-pocket cost can run as high as $10,000 a month. And many patients are on these drugs perpetually to keep their cancer at bay, so the costs can add up fast.
As expensive new TKIs continue to roll out and are advertised widely to doctors and patients, researchers within the Hutchinson Institute for Cancer Outcomes Research, or HICOR, investigated whether these new drugs are providing value to the people who need them. HICOR research is used to inform potential changes in policy and clinical practice.
The results were clear. Cancer patients, especially those on Medicare, are not benefitting from these TKIs in a way that aligned with their cost.
“The extraordinarily high price of each generation of TKIs not only increases the severe financial burden on patients with cancer but often results in poor compliance or patients stopping them early,” said Dr. Gary Lyman, HICOR’s senior lead for healthcare quality and policy. “That adversely affects the actual survival of patients with treatable and potentially curable malignancies.”
In other words, high costs are leading patients to give up on the drugs — and it’s costing some of them their lives.
TKI price: a hard pill to swallow
In a study published Monday, HICOR researcher Dr. Bernardo Goulart, who treats lung cancer patients at the Hutch’s clinical care partner Seattle Cancer Care Alliance, looked at TKI use in metastatic non-small cell lung cancer and found a discouraging trend.
Stage 4 lung cancer patients with mutations that respond well to TKIs stopped taking them after a few months. Not because of harsh side effects, because they were too expensive.
Goulart said for these particular drugs, there was a “strong association of high patient out-of-pocket expenses … with worse survival, lower drug adherence, and increased risk of stopping the oral drugs prematurely.”
“Some patients can’t afford these life-prolonging medicines,” he said. “Their outcomes are undermined be the tradeoff decisions they have to make. Do they take less of the drug and afford basics? Or take the drug regularly and forego basic needs like food and clothing?”
Goulart said he’s had “multiple situations” where the patients tell him the drugs are completely unaffordable.
“They tell us up front they cannot pay for it,” he said. “They can’t even afford the copay.”
While some institutions like SCCA have financial navigators who help patients apply for assistance or charity care, these resources aren’t available to everyone in Washington state.
“What happens to patients who are treated in remote clinics that don’t have the programs we have?” Goulart asked.
Martha Lane, a 66-year-old metastatic lung cancer patient from Bellevue, Washington, said she was “completely astounded” when she learned how much her TKI was going to cost.
“At $20,000 a month, it’s unaffordable to all but the wealthiest,” she said. “It was frightening to face taking a drug that while it might save my life, could also bankrupt me in the process.”
Fortunately, Lane was able to get assistance both from a financial navigator and through her TKI’s drugmaker, AstraZeneca. But she acknowledges things could have gone much differently.
“Had they not made it available at no cost, the thought of selling our property popped into my mind,” she said. “The only other viable option would have been not taking it.”
Lifesaving drugs — for a few
HICOR’s new retrospective analysis, published in the Journal of Clinical Oncology’s Oncology Practice, used the Cancer Surveillance System, a state subset of the larger SEER national cancer registry, and HICOR’s insurance claims database to identify lung cancer patients diagnosed between January 2010 and the end of 2015. The HICOR team included senior author Goulart as well as HICOR director Dr. Scott Ramsey and Drs. Joe Unger, Shasank Chennupati and Catherine Fedorenko.
Researchers used a natural language processing algorithm to scan pathology reports within the CSS registry for patients who’d been prescribed TKIs for their EGFR- and ALK-driven metastatic non-small cell lung cancer. EGFRs are epidermal growth factor receptors and ALK is an anaplastic lymphoma kinase; these mutations respond well to kinase inhibition via TKIs.
They identified 105 patients and went on to analyze their out-of-pocket costs, adherence to treatment and cancer outcomes. Patients were divided into four groups, based on their out-of-pocket costs for their first three months of their oral TKI drugs.
“We categorized them into quartiles of how much they spent on average for the first three months,” Goulart said.
The first quartile was the lowest cost; the second, the second lowest, and so on. Then they compared how those with the fourth-highest cost quartile did against the other three groups combined. Were they able to continue taking their meds? What happened to them?
As it turned out, the higher the TKI out-of-pocket costs, the more patients cut back; the more they quit taking the drugs altogether — and the more they died.
And Medicare patients fared worse by a significant margin.
These patients paid more and took less of their oral TKI therapies than those with commercial insurance. Median monthly out-of-pocket cost for Medicare patients in the combined group was $1,618 compared to the big-bucks bucket where patients had to pay out-of-pocket costs of $4,084.
Those with commercial insurance paid much, much less — if anything. Their cost ranged between a median of zero and $1,618 per month for their TKIs.
Of the 21 patients, or 20%, who quit taking their TKI within three months, 16 were Medicare beneficiaries; five were commercially insured. Over the course of two years, 92 of the 105 patients died. Sixty of them were Medicare beneficiaries.
“The extraordinarily high price of each generation of TKIs not only increases the severe financial burden on patients with cancer, but often results in poor compliance or patients stopping them early.”
Fred Hutch public health researcher Dr. Gary Lyman
Policy change to save lives
“The association of higher out-of-pocket costs and lower survival were all driven by the Medicare patients, not the commercially-insured patients,” Goulart said. “If the findings hold true in larger studies, the implications of policy changes should be focused on the Medicare Part D program.”
What’s the issue with Medicare’s prescription drug benefit program? The federal government can’t negotiate Part D drug prices with drug companies, although other federal agencies, like the Department of Veterans Affairs can and do, and to great effect. Since the Centers for Medicare and Medicaid Services, or CMS, can’t negotiate a price for cancer drugs, the pharmaceutical companies get to set the price.
”Without a walkaway option from Medicare, the prices are based on what pharmaceutical companies consider a fair market price,” Goulart said.
And other restrictions stand in the way. Patients with Medicare can’t apply for third party assistance programs, although patients with commercial insurance can and do.
If they could, “they might receive the drug for free or at much lower costs,” Goulart said.
Instead, somebody who’s retired and has a tiny bit of money tucked away with access to these specialty drugs through Medicare Part D, will face much higher out-of-pocket costs.
“This population which is already poor to begin with — these are probably the ones who had lower survival,” he said.
To Goulart, it’s clear what needs to be to be done.
“It’s flawed legislation and needs to change,” he said. “CMS needs to have the bargaining power to negotiate drug pricing for all cancer drugs. We need to reform our copayment policies, as well. If we lower the costs of these medicines, patients may live longer.”
Newer drugs, higher prices
HICOR’s Dr. Gary Lyman and others from the Hutch, the University of Washington and Seattle Children’s collaborated on a trio of studies that showed patients are also taking pricier TKIs than they might need, even when a cheaper effective generic is available. The study was part of a larger collaboration between HICOR’s Lyman and Chennupati; pediatric cancer researchers Drs. Eric Chow, Jennifer Wilkes, Dr. Lena Winestone and Dr. Henry Henk of OptumLabs Cancer Research Collaborative.
Published in a research letter in JAMA Oncology, they showed a steady climb in the number of CML patients taking next-generation TKIs. The drugs — dasatinib, nilotinib, bosutinib and ponatinib — all prevent unregulated cell growth in this type of leukemia.
Unfortunately, a previous study showed TKIs are the largest driver of health care costs in patients with CML, representing 66% of the first-year spending for both Medicare patients and those covered by commercial insurance. Despite this, and the availability of the generic TKI, imatinib, many CML patients received a next-gen TKI, the team found. Further, many were switched from the generic to a next-gen TKI without the “molecular monitoring” needed to inform such a decision.
Lyman’s latest analysis showed CML patients are regularly “trading up” their TKIs: in 2010, 19% of CML patients opted for the newest drugs; by 2019, the figure had climbed to over half, 56%.
This is a problem, Lyman said, because “no study has yet shown patient survival is improved with the much costlier agents.” Lyman said new TKIs often have a higher rate of side effects, as well.
Imatinib, the first generic TKI, was released in 2016. Each daily tablet can be had for as low as $20, while the average next-gen TKI drug costs $350 per day.
Still, around one in four patients switched to a pricier TKI within their first of year of treatment. Between 2010 and 2018, use of these pricier drugs by the end of the first year of treatment went from 34% to 64%.
Are patients asking for them because they’re new? Are doctors using them for the same reason?
“Most patient rely on the recommendation of their oncologist who is influenced heavily by pharma detailing [a one-on-one marketing strategy used by pharmaceutical companies] and the desire to use the latest thing in their practice,” Lyman said, adding there’s “some evidence” pointing to a longer remission period with the next-gen TKIs.
“Patients will not benefit from the drugs if they can’t pay for them.”
Fred Hutch health outcomes researcher and oncologist Dr. Bernardo Goulart
Higher prices, less survival
Adherence, being able to keep up your treatment, matters in cancer therapy. For these newest treatments, though, adherence may force people to forgo fundamentals like groceries or rent; sell the family home or declare bankruptcy.
Prices for these drugs have risen steadily since their introduction in 2001. These rises, which Lyman calls obscene, are part of a much larger pattern of health care dysfunction in the U.S. While every other industrialized nation has lower costs and higher life expectancy, the U.S. health system offers the opposite: higher prices and lower life expectancy.
“National policies that truly address rising cancer drug prices and overall healthcare costs have to be of the highest priority for everyone including our political leaders,” Lyman said.
Goulart put it more bluntly.
“Patients will not benefit from the drugs if they can’t pay for them,” he said. “To protect the patients, we really need policy change.”
Funding for the three CML TKI studies was through the nonprofit Stand Up To Cancer, managed by the American Association of Cancer Research, or AACR. The TKI study involving NSCLC was funded by the National Cancer Institute.
Diane Mapes is a staff writer at Fred Hutchinson Cancer Research Center. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor, she blogs at doublewhammied.com and tweets @double_whammied. Email her at dmapes@fredhutch.org.
Source: Hutch News Stories
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