Σάββατο, 31 Δεκεμβρίου 2016

QUESTIONABLE EFFICACY OF NEW CANCER DRUGS

Another analysis of new cancer medicines again raises serious questions about whether these hugely expensive agents offer any measurable benefit for patients in the real world of cancer care. It finds that among new cancer drugs approved between 2003 and 2013, up to one in five have no benefit for the patient.
Two other recent analyses have recently questioned benefitsand even ethics of new cancer drugs, as previously reported by Medscape Medical News.
The new analysis was published online December 29 in JAMA Oncology.
Lead author Sebastian Salas-Vega, MSc, London School of Economics and Political Science, United Kingdom, and colleagues, looked at 62 new cancer agents approved by the US Food and Drug Administration (FDA) and the European Medicines Agency between 2003 and 2013.
The authors evaluated the influence of 53 of these drugs on clinical outcomes as assessed by English, French, and Australian health technology assessment agencies through to May 2015.
"We extracted and reviewed summary conclusions of drug-related OS [overall survival], QoL [quality of life], and safety benefits" from health technology assessment documents.
"We find that OS benefits vary widely, improvements in OS and QoL often come at the cost of safety, and there are reasons to doubt whether clinical efficacy has been matched by effectiveness in the real world," the investigators comment.
"In all cases where OS gains could be quantified, new cancer drugs produced a total mean...improvement in OS of 3.43 months...relative to treatments that were available in 2003," the study authors conclude.
Fewer than half (43%) of the cancer drugs evaluated were found to increase OS by at least 3 months, they add.
A further 11% of the 53 drugs evaluated increased OS by less than 3 months, while 15% had an indeterminate effect on OS.
"The remaining 16 (30%) cancer drugs did not demonstrate an increase in OS over alternative treatments," the researchers indicate.
The new cancer drugs' effect on OS also differed significantly depending on the cancer for which they were indicated.
For example, drugs targeting thyroid cancer or ascites had zero effect on OS, while those used for renal cancer increased OS by an average of 6.27 months and those for breast cancer by an average of 8.48 months.
Changes in Quality of Life 
Dr. Salas-Vega and colleagues also investigated whether the same 53 new cancer drugs changed QoL in any meaningful way for patients.
They found that 42% of the drugs in fact did improve QoL, but about half (53%) had no measurable effect on it, at least not when compared to the best alternative treatment.
They also found that only 45% of the new drugs evaluated reduced patient safety, while evidence regarding their safety was mixed for another 19% of the new drugs overall
"As it stands, 1 in 3 (33%) of all newly approved cancer medicines are not associated with any OS benefit, while 1 in 5 (20%) neither extend life nor improve QoL or safety," the study authors observe.
"These findings suggest that expenditures for up to 1 out of every 5 new cancer drugs may be spent without any OS, QoL or safety benefit to the patient," they add.
Nevertheless, the authors conclude that it is "encouraging" that 43% of new cancer drugs extend life by 3 or more months, an amount that both British and Australian authorities consider clinically meaningful.
"While perhaps modest, this OS benefit represents an important step forward for patients and society, as even minor improvements in survival can have an effect on reducing mortality at the population level," they conclude.
Different Viewpoint
However, other researchers who have also examined the worth of new cancer drugs would likely beg to differ.
Another recent analysis, conducted by Vinay Prasad, MD, MPH, senior scholar, Center for Health Care Ethics, Oregon Health and Sciences University, Portland, and Chul Kim, MD, MPH, fellow in medical oncology, National Cancer Institute, Bethesda, Maryland, looked at 36 new cancer drugs approved by the FDA between 2008 and 2012.
The authors found that only 5 of the 36 drugs improved OS.
They also found that QoL had not been studied for over half of 18 new cancer drugs they evaluated. Indeed, only 1 of them, crizotinib (Xalkori, PF Prism CV), was associated with a measurable improvement in QoL
similar analysis of these same new drugs found that many were approved by the FDA on the basis of surrogate endpoints and that they have retained their approval status and remain available to prescribing physicians even when postmarketing studies show that the new agents do not extend OS or improve QoL compared with placebo or observation groups.
That analysis, by Tracy Rupp, PharmD, MPH, and Diana Zuckerman, PhD, both from the National Center for Health Research, Washington, DC, was published online November 29 in JAMA Internal Medicine.
"The FDA should promptly withdraw approval for cancer drugs that are proven to have no clinical benefit," declared Scott Bauer, MD, and Rita Redberg, MD, both from the University of California, San Francisco, in an accompanying editorial.
"Removing these drugs, each of which costs between $20,000 and $170,000 per year, from the market will improve the quality and value of cancer care," they added.
In another recent paper, Peter Wise, MD, former consultant physician at Charing Cross Hospital and Imperial College School of Medicine, London, United Kingdom, questioned the ethics of using hugely expensive drugs for marginal gains in OS.
"Spending a six figure sum to prolong a life by a few weeks or months is already unaffordable," he wrote.
But it is also "inappropriate," he argued, given that these huge sums could be spent more appropriately elsewhere.
"I can understand that people would want to live an extra few months but I do not think that it should be at the expense of the community," Dr Wise said in a BMJ article published earlier this year.
As he suggested, many of these new drugs cost more than $100,000 per year for the drug alone, a steep price indeed for the promise of a few additional months of survival for a given patient.
However, not all oncologists agree with such a pessimistic view of new cancer drugs.
Commenting on Dr Wise's viewpoint, Len Lichtenfeld, MD, deputy chief medical offer from the American Cancer Society, argued that new targeted and immune therapies now approved for melanoma, for example, have produced meaningful improvements in both survival and QoL.
"We cannot dismiss that there has been progress...and I do not agree with the statements that patients do not uniformly do well on these drugs and that they don't prolong survival," Dr Lichtenfeld said.
Dr Lichtenfeld also pointed out that some of the newer therapies are substantially less toxic than the drugs given in the past, allowing patients to enjoy a good QoL while receiving cancer care.
Salas-Vega and colleagues' study was funded by LSE Health and the Institute of Global Health Innovation, Imperial College London. None of the authors cited have disclosed any relevant financial relationships.
JAMA Oncol. Published online December 29, 2016

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