Σάββατο, 25 Μαρτίου 2017

REDUCE CANCER DRUG COST BY AVOIDING LOW VALUE OPTIONS

Oncologists can help reduce the costs of treating cancer by favoring drug regimens that have proven value over more expensive alternatives, especially when evidence supporting many of these alternatives is weak, an opinion piece by Bishal Gyawali, MD, Nobel Hospital, Kathmandu, Nepal, suggests.
"Discouraging low-value practices in oncology clinics remains [an] important but often overlooked measure that can help reduce financial toxicity not only to the individual patient, but also to the entire health care system," he writes.
"If we are serious about addressing the financial toxicity of cancer treatment, deimplementing costly but ineffective practices are the first steps," he adds
The opinion piece was published online March 16 in Ecancermedicalscience.
Reducing cost does not mean compromosing oncologic outcomes, Dr Gyawali argues.
As an example, he identifies the use of ramucirumab (Cyramza, Lilly) in the second-line treatment of metastatic colorectal cancer – for which it has been approved by the US Food and Drug Administration (FDA) – as a key offender in what he describes as a "low-value" practice in oncology.
Dr Gyawali argues that after disease progression on first-line therapy for metastatic colorectal cancer with FOLFOX (oxaliplatin, leucovorin, and fluorouracil) plus bevacizumab (Avastin, Genetech/Roche), the preferred second-line therapy should be FOLFIRI (folinic acid, fluorouracil, and irinotecan) plus bevacizumab, and this "should be preferred over the FOLFIRI + ramucirumab regimen as the second-line therapy," he writes.
His reasoning behind this is simple: the use of bevacizumab following disease progression is well supported by evidence, bevacizumab is significantly cheaper than ramucirumab, and, given that both drugs are angiogenesis inhibitors, they share a similar toxicity profile.
Moreover, bevacizumab should be the preferred choice in the first-line treatment of right-sided metastatic colorectal cancer, because several analyses now indicate that anti–epithelial growth factor receptor (anti-EGFR) antibodies such as cetuximab (Erbitux, Bristol Myers-Squibb/Eli Lilly) are not very effective in this setting. 
Again, there is a big price difference – the cost of a dose of cetuximab is double that of bevacizumab, he notes.
Nor is there any role for the concurrent use of anti-EGFR antibodies with radiotherapy in locally advanced head and neck squamous cell carcinoma (LAHNSCC).
"Concomitant platinum-based chemoradiotherapy has been the standard of care in the management of LAHNSCC," Dr Gyawali points out.
An earlier trial did show that cetuximab could be helpful when given in combination with radiotherapy in LAHNSCC.
But as Dr Gyawali points out, this trial compared cetuximab plus radiotherapy with radiotherapy alone, not against a standard-of-care, platinum-based regimen.
In fact, only one phase 3 trial provided data favoring the use of cetuximab in LAHNSCC, whereas multiple trials support the standard platinum-based approach, he notes.
Furthermore, the addition of another anti-EGFR agent, panitumumab (Vectibix, Amgen) to standard fractionation radiotherapy plus cisplatin in the treatment of LAHNSCC did not confer any benefit either in the CONCERT-1 trial or the CONCERT-2 trial.
Dr Gyawali points out only marginal evidence supports the use of ramucirumab as a single agent in the treatment of second-line gastric cancer, for which it is also FDA approved.
But here again, ramucirumab was tested against placebo, not against either a taxane or irinotecan, which are recommended for second-line gastric cancer.
"Even then, the drug marginally improved survival over placebo by 1.4 months," Dr Gyawali writes.
"Is there any value in prescribing this $13,000 per month drug that provides a survival of only 5.2 months?
Dr Gyawali also argues against using sunitinib (Sutent, Pfizer Inc) for the adjuvant treatment of renal cell carcinoma. Although the S-TRAC trial has shown a benefit in disease-free survival with 1 year of adjuvant sunitinib (N Engl J Med. 2016;375:2246-2254), a well-powered trial conducted previously failed to show similar benefit (Lancet. 2016;;387:2008-16), and an improvement in overall survival has not yet been reported. A meta-analysis of these two studies showed no evidence of benefit in disease-free survival and possible harm in overall survival in the setting of renal cell cancer.
A 1-year course of sunitinib also costs in excess of $60,000, he points out.
It is not only drug therapy that adds layers of cost to cancer therapy, Dr Gyawali notes.
Another example of low-value cancer care, he maintains, is the use of CA-125 testing for surveillance in ovarian cancer. Basing early treatment of relapse only on an elevation in the concentration of CA-125 was not found to confer any survival benefit. And yet a recent study (JAMA Oncol. DOI: 10.1001/jamaoncol.2016.1842) showed that physicians have continued to order these tests. An editorial that accompanied the Lancet article referred to the such use of CA-125 testing as the ""fatal attraction of more information."
The cost of such surveillance is not trivial, Dr Gyawali notes: for the US population, the cost of CA-125 testing alone was estimated to be $1,999,029 per year; when CT scans were added, the cost was estimated to be $16,194,647 per year.
"If we are serious about addressing the financial toxicity of cancer treatment, deimplementing costly but ineffective practices are the first steps," he observes.
No Recommendations
The final 2 examples of low-value oncology are unfortunately fairly ubiquitous despite recommendations against them.
Dr Gyawali notes that several guidelines have argued against the use of granulocyte-colony-stimulating factors (CSFs) for prophylaxis of febrile neutropenia in low-risk patients, and no guidelines suggest that CSFs should be used for the treatment of febrile neutropenia except in high-risk patients.
"Notwithstanding these recommendations, using CSFs has been a knee-jerk reaction to febrile neutropenia in oncology practice in many institutions," Dr Gyawali states.
"Thousands of dollars wasted for non–evidence based, not-recommended practice," he adds.
Moreover, studies have proven the futility of giving chemotherapy to patients whose life expectancy is less than 6 months.
Yet, as Dr Gyawali argues, oncologists frequently persevere in giving chemotherapy despite the fact that it has no benefit in this setting.
Although he empathizes with oncologists who wish to err on the side of doing something, "we should understand that using chemotherapy in a dying patient is futile in terms of both expenses and quality of life," he writes.
"Irrespective of financial toxicity, no patient deserves to be under chemotherapy in the final days of his life," he argues.
Dr Gyawali has disclosed no relevant financial relationships.
Ecancermedicalscience. Published online March 16, 2017. Full text

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