El costo de las drogas debe ser parte del tratamiento

En una presentación de ASCO 2015 se analiza bevacizumab vs.cetuximab y los importantes costos que conlleva en el tratamiento del cáncer colorrectal, así como la toxicidad inducida.
Esto debería ser tenido en cuenta ya que el agregado de estas drogas a la quimioterapia,si bien es estadísticamente significativa en cuan a progresión libre de enfermedad o supervivencia, no es clínicamente muy relevante

Cost of Cancer Drugs Should Be Part of Treatment Decisions

JUNE 1, 2015

Treatment decisions are based on a hierarchy of factors. Drug effectiveness is considered to be the most important, followed by toxicity, and, lastly, cost. Yet, during the Saturday, May 30, Health Services Research and Quality of Care Oral Abstract Session, discussant Peter B. Bach, MD, of Memorial Sloan Kettering Cancer Center, asked, “Why treat prices as immutable? Would we really pay an infinite amount for a microscopic benefit?” A discussion of how cost does not necessarily reflect drug value, efforts to consider cost as part of the treatment decision, and methods to set new cancer drug prices based on value were the focus of the session.

Since 1965 when Medicare was created, the introductory cost of new cancer drugs has increased 100-fold to approximately $10,000 a month (adjusted to 2014 dollars). Older drugs also contribute to soaring costs; the price of imatinib has risen from less than $100 per day in 2004 to more than $200 in 2014. Meanwhile, the Centers for Medicare & Medicaid Services (CMS) began applying a value-based payment modifier for physician groups in 2015, under which payments will be determined by the quality of patient care balanced against the cost of care.

Balancing Cost with Efficacy, Toxicity

The CALGB/SWOG 80405 trial, begun in 2005, aimed to determine if the addition of cetuximab to leucovorin/fluorouracil/irinotecan (FOLFIRI) or leucovorin/fluorouracil/oxaliplatin (FOLFOX) chemotherapy prolongs survival compared to FOLFIRI or FOLFOX with bevacizumab in patients with metastatic colorectal cancer. From the outset, the trial included an economic companion study of bevacizumab and cetuximab.

Dr. Deborah Schrag

The direct cost of bevacizumab and cetuximab for one 8-week cycle in an average patient could easily be determined based on the price of the two antibodies: $9,324 and $20,856, respectively (2014 drug cost). However, as Deborah Schrag, MD, FASCO, of the Dana-Farber Cancer Institute, explained, the cost of these treatments could be driven by additional factors, such as differences in adverse events and consequent differences in hospitalization rates (Abstract 6504). Thus, Dr. Schrag and her colleagues looked at measures, such as days in the hospital/intensive care unit and Medicare costs for particular services associated with these drugs, along with overall survival and quality-adjusted survival (based on EQ-5D health questionnaires) to determine cost effectiveness and cost utility, respectively.

Table 1. Mean Cost Differences Based on Rx Arm Stem from Antibody Costs
	Bevacizumab 559 patients	Cetuximab 578 patients	Cost Difference Bev-Cetux (95% CI)
FOLFOX/FOLFIRI	$2,894	$2,616	$277 (163 to 718)
Antibody Rx	$33,500	$71,718	$-38,217 (-41,050 to -31,384)
Hospital/ Acute Care	$28,951	$29,494	$-543 (-2,830 to 1,745)
Estimated Total Costs	$66,075	$105,339	$-39,264

Dr. Schrag explained that there was no difference in the survival outcomes or quality-adjusted life years (QALY) between the two treatment arms. In contrast, the economic study found a large difference in total cost of treatment between the groups: $66,075 in the bevacizumab group compared with $105,339 in the cetuximab group. The cost difference was $39,264 (95% CI). This difference arose largely because of the difference in costs of bevacizumab and cetuximab, whereas the costs of FOLFOX and FOLFIRI and hospital/acute care were similar (Table 1).

“Because survival and quality of life are similar but cost is less, and because patients have significant out-of-pocket costs, I think there’s a good argument to be made that bevacizumab should be the first-line treatment. It’s certainly what I use in my practice,” Dr. Schrag said.

Dr. Bach was critical of the tendency for clinical oncologists to accept the high price of drugs like cetuximab that have similar efficacy and toxicity to less expensive medications. “Why not close the loop?” Dr. Bach said. “Dr. Schrag says no in clinic, but why not say no more generally?”

Dr. Schrag noted that because ASCO is committed to improving quality and value in cancer care, ASCO and CMS could work together to determine preferred treatment regimens, which have been established for other conditions. Although she explained that bevacizumab is a “no-brainer” from a value perspective, cetuximab plus chemotherapy should be available for patients who want to pay for it, and that there could be clinical settings for which it would be preferred. She added that these monoclonal antibody therapies will go off-patent in the next few years, and at that time it will be interesting to see how companies price their biosimilars.

Setting Cost Based on Value

Daniel A. Goldstein, MD, of the Winship Cancer Institute of Emory University, argued for cost-effectiveness analyses prior to drug approval so that these data could help establish the cost of the drug (Abstract 6505). Performing these analyses after approval is “an academic exercise of no meaningful consequence,” he said.

Dr. Goldstein and his colleagues evaluated the cost at which necitumumab could be considered cost-effective. Necitumumab, an EGFR inhibitor, met its endpoint in the phase III SQUIRE trial of patients with advanced squamous non–small cell lung cancer and resulted in a median overall survival benefit of 1.6 months. Dr. Goldstein and colleagues determined cost based on the incremental cost-effectiveness ratios (ICER), or willingness-to-pay values, that are commonly reported for countries such as the United States. Given an estimated ICER range of $50,000/QALY to $200,000/QALY, cost acceptability curves could be modeled that take into account estimated QALY for the drug and variables, such as adverse events, outpatient follow-up, and drug cost. Dr. Goldstein and his colleagues determined that price tags on necitumumab of $563-$1,309 per 3-week cycle would maintain ICERs below $100,000/QALY and $200,000/QALY, respectively.

Setting drug price based on cost/QALY could be important when there are uncertainties about the superiority of one drug over another, such as the small and not statistically significant overall survival benefit of cetuximab compared with bevacizumab in the CALGB/SWOG 80405 trial. “Those small differences can be priced in, and then we can all sleep at night,” Dr. Bach said.

During the discussion, an audience member noted that he might not have received the stem cell therapy that has made him cancer free if quality considerations were made, and he urged the presenters to be very specific when they discuss quality and what it means for different patients. In response, Dr. Goldstein said that the “aim is to deliver the best possible care that is valuable to patients, but necitumumab and many drugs have not cured any patients. When drugs are curative, then that changes the ICER significantly.”