Impact of a chemoresponse assay on treatment costs

[gpawelski]

Impact of a chemoresponse assay on treatment costs for recurrent ovarian cancer.

Havrilesky LJ, Krivak TC, Mucenski JW, Myers ER.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC.

Objective

We sought to estimate mean costs of chemotherapy treatment for recurrent ovarian cancer with or without use of a chemoresponse assay.

Study design

We estimated mean costs for 3 groups: (1) assay assisted: 75 women who received oncologist's choice of chemotherapy following chemoresponse testing (65% adherence to test results), (2) assay adherent: modeled group assuming 100% adherence to assay results, and (3) empiric: modeled from market share data on most frequently utilized chemotherapy regimens. Cost estimates were based on commercial claims database reimbursements.

Results

The most common chemotherapy regimens used were topotecan, doxorubicin, and carboplatin/paclitaxel. Mean chemotherapy costs for 6 cycles were $48,758 (empiric), $33,187 (assay assisted), and $23,986 (assay adherent). The cost savings related to the assay were associated with a shift from higher- to lower-cost chemotherapy regimens and lower use of supportive drugs such as hematopoiesis-stimulating agents.

Conclusion

Assay-assisted chemotherapy for recurrent ovarian cancer may result in reduced costs compared to empiric therapy.

Key words: chemoresponse assay; cost analysis; ovarian cancer

PMID: 20417480

http://www.ncbi.nlm.nih.gov/pubmed/20417480

[gpawelski]

It amazes me not only that some private insurance carriers don't like to pay for oncologic in vitro chemoresponse assays but that they don't emphatically mandate it as a requirement for obtaining chemotherapy reimbursement against ill-directed treatments. Evidence in support of these tests is more than sufficient to justify them.

Profit, as we have seen, is a powerful motivating force. Among the private payors, at least, the profit motive is entirely consistent with the goal of the tests, which is to identify efficacious therapies irrespective of drug mark-up rates.

Everyone is scared to death - and rightly so - at what is going to happen to the healthcare economic system with increasingly expensive new drugs that benefit only a small percentage of patients who receive them. Hence the headlong rush to develop companion diagnostic tests to identify molecular predisposing mechanisms whose presence still does not guarantee that a drug will be effective for an individual patient.

The pressure, in fact, is so great that these molecular companion diagnostics they've approved often have been mostly or totally ineffective at identifying clinical responders (durable and otherwise) to the various therapies. Nor can they, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class.

The FDA could benefit too, as they find themselves under increasing pressure to allow new drugs into marketplace while at the same time protecting the safety of potential recipients of those drugs as well as the financial interests of those who will have to pay for them.

I think that in both of these areas - private insurance carriers and the FDA - there is a very real opportunity to make a substantial impact and contribution, an interest in saving the healthcare system perhaps billions of dollars a year by ensuring that expensive treatments are used appropriately.

Committee chairpersons, committee members and persons in congress who may have personal interests not only in discovering new cancer treatments - everybody wants that - but also, in the "here and now," using currently-available cell culture assay technologies to improve the effectiveness of existing drugs and save lives today by administering the right drug to the right patient at the right time.

The validaton standard that private insurance companies are accepting from molecular profiling tests is accuracy and not efficacy. The "bar" had been instantly lowered. No longer will it be essential to prove that the use of a diagnostic test improves clinical outcomes, all they have to do for these molecular profiling tests is prove that the test has a useful degree of accuarcy. However, the validation standard wanted for functional tumor cell profiling is efficacy. What's good for the goose is good for the gander.

[Barb73]

Greg,

I have been reading your postings about the use of an assay for patients to determine more effective treatments, and in the long run, to lower costs.

Simply put, why is that you think this is not being done on a routine basis? After all, as you pointed out, it would be advantageous in a monetary sense.

My take is that patients might feel that they would not be given enough options for their treatments.

The perception of lack of effective treatments on the part of those not receiving more "attempts" by their oncologists might put the stress on the research/medical community.

Barbara

[gpawelski]

Barbara

Good questions!

One unique result of this study presented the fact that lower cost drug regimens can be more effective than higher cost drug regimens and the less need to use supportive drugs (lower toxicity profiles). When assays are used, costs can be lowered and less severe side effects can be achieved. The chemoresponse assay used in this study was a "cell-death" endpoint assay (the most up-to-date of the assays).

The assays haven't really been understood by many NCI investigators and by NCI-funded university investigators because their knowledge was almost always geared toward an assay technique (cell-growth) that hasn't been used in private labs for twenty years.

Just recently, the National Comprehensive Cancer Network (NCCN) updated the NCCN Clinical Practice Guidelines for Oncology to include the use of chemoresponse assays.

The NCCN states that chemoresponse assays are being used in some NCCN member institutions for decisions related to future chemotherapy in situations where there are muliple equivalent chemotherapy options available.

Recent studies presented at ASCO and published in the International Journal of Gynecologic Cancer evaluated the association between prediction of response to chemotherapy and progression-free interval and overall survival in ovarian cancer.

The CEO of the Ovarian Cancer National Alliance stated that not only are oncologists recognizing the benefits of using chemoresponse assays when faced with equivalent therapeutic options, they are also paving the way for greater support of personalized medicine in oncology.

NCCN Clinical Practice Guidelines in Oncology are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of physicians from NCCN member institutions.

Critics of the cell-based assay procedure contend that cells do not necessarily react the same in the laboratory (in vitro) as they do in the body (in vivo). However, "cell-death" assay tests are performed using intact, living cancer cells plated in 3D microclusters, which is indicative of what will happen in the human body. Three-dimensional microclusters of tumor cells are isolated from fresh tumor biopsy specimens and cultured for 96 hours (polypropylene, round-bottomed, 96-well microplates) in the presence and absence of test drugs.

I have tried to raise the awareness that the systematic procedure of cell culture assay technology exists and might be very valuable. Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant. Eliminating agents that are "resistant" to the tumor is a good start.

When clinically relevant and accepted drugs may have the same efficacy, and a tumor is "resistant" to one of them, it is within the "standard of care" to give the drug with the least "resistance" and/or the drug with the most "sensitivity."

My personal belief is in having additional support of drug patient-specific activity as determined by extensive laboratory pre-tests to bolster the clinical justification of the drug(s) chosen, with no economic ties to outside healthcare organizations; recommendations made without financial or scientific prejudice.

[ts]

Isn't this what the press release from Moffitt Cancer Center addressed last week?

http://www.miamiherald.com/2010/04/23/1 ... unces.html

I thoght it was already posted, but maybe "in the news" rther than under this topic.

[gpawelski]

ts

No. Cell-based chemoresponse assays, using "cell-death" endpoints are entirely different than gene expression testing. Cell-based assays offer more promise than do current tests for the gene expressing enzymes such as ERCC1. While markers like ERCC1 may have some relevance, the complexity of cell biology, the need to assess synergy and the need to assess sequence dependence can only be done today in "real-time" cellular platforms.

While ERCC1 is increasingly measurable, it's only one of a whole collection of enzymes that need to be assessed. You need to look at the interplay between enzymes, the presence or absence, and you also have to consider "functional" activity (is the cell being killed regardless of the mechanism of "live" cells), as opposed to "target" activity (does the cell express a particular target that the drug is supposed to be attacking).

While a "target" assay tells you whether or not to give "one" drug, a "functional" assay can find other compounds and combinations and can recommend them from the one assay. Functional profiling with cell-based assays can discriminate between the activity of different "targeted" drugs and identify situations in which it is advantageous to combine the "targeted" drugs with other types of cancer drugs.

Targeted drugs are specifically designed to block one or more critical pathways (EGFR, KRAS, ALK, etc.) involved in cancer-cell growth and metastases. The development of these therapies stem from advances in molecular biology that have permitted the identification of qualitative and quantitative differences in gene expression between cancer cells and normal cells.

The new agents range from antibodies to small molecules. The interaction of the antibody or drug with its target inhibits pathways that are essential for cell proliferation or metastasis or activates pathways that culminate in cell death (apoptosis). Since these targets are usually specific for or overexpressed in cancer cells, the new agents generally have fewer side effects than most conventional chemotherapeutic agents.

However, testing for these pathways (molecular profiling), those which identify DNA, or RNA sequences or expression of individual genes or proteins often examine only one component of a much larger, interactive process. It doesn't matter if there is a target molecule in the cell that the targeted drug is going after. If the drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, drug resistance is multifactorial.

Even knowing what genes the drugs target doesn't tell you the whole story. All the mutation studies can tell you is whether or not the cells are "potentially susceptible" to this pathway of attack. It doesn't tell you if one inhibiting drug is better or worse than another which may target the mutation. In different tumors, either one inhibiting drug might get in better or worse than another. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.

You can though take the advantage of profiling the entire cell to measure the interaction of the entire genome (not just one pathway or a couple of pathways). There are many pathways to altered cellular (forest) function (hence all the different "trees" which correlate in different situations).Functional profiling the whole cell measures what happens at the end (the effects on the forest), rather than the status of the individual trees.

Cancer is a complex disease and needs to be attacked on many fronts. Improving cancer patient treatment through proper drug selection will enable oncologists to prescribe treatment more in keeping with the heterogeneity of the disease. The biologies are very different from patient to patient and the response to given drugs is very different.

[gpawelski]

There has been more evidence that wide-scale adoption of chemoresponse assays would help not just patients, but consumers and insurance companies as well.

In June 2009, DiaTech Oncology presented a paper on this topic at the annual meeting of the American Society for Clinical Oncology (ASCO).

The studied the claims for lung, breast, colon or ovarian cancer patients among the 48,927 employees of a large self-insured corporatlion. There were 196 patients who developed these forms of cancer during a three and a half year period.

The total treatment cost was $5,647,165, of which the cost of anticancer drugs was $1,149,404. But when only drugs that were active in their proprietary form of assay, the average savings was impressive.

The authors reported that treatment with the assay could save a high percentage of chemotherapy costs as well as a substantial percentage of overall costs of cancer care for such organizations.

The savings varied from 9.9% to 62.7% depending on effectiveness and duration of the treatment for different types and stages of cancer. But the true economic value of treatment that is guided by the assay would be higher, since use of active chemotherapy could increase quality of life and employment and reduce disability and side effects.

The value of personalized treatment (Rx) planning (PTP): Cost savings (sav) by the microculture kinetic (MiCK) chemosensitivity (CS) assay, evidence from a large American self-insured company (ASIC)

Sub-category: Health Services Research

Category: Health Services Research

Meeting: 2009 ASCO Annual Meeting

Session Type and Session Title: abstract not presented at the 2009 ASCO Annual Meeting but has been published in conjunction with the meeting.

Abstract No: e17541

Citation: J Clin Oncol 27, 2009 (suppl; abstr e17541)

Author(s): R. G. Latimer, C. A. Presant, A. E. Hallquist, M. Perree, D. Agapitos; DiaTech Oncology, Brentwood, TN; Wilshire Oncology Medical Group Inc., West Covina, CA; DiaTech Oncology, Montreal, QC, Canada

Abstract:

Background:

Costs of cancer (CA) patient (PT) Rx are high. A novel CS assay MiCK was predictive of chemotherapy (CT) activity and survival in leukemia PTs (Blood. 2001;98:241b) and is in solid tumor testing. We performed a cost sav analysis for CS assay in a large ASIC population.

Methods:

An ASIC of 48,927 employees submitted 3.5 years claims data on all PTs with diagnoses of CA lung, breast, colon or ovary. Analysis of average Rx costs was made based upon total CT usage, Rx of selected PTs including therapeutic drug administration (admin), CT admin, supportive care (SC) drugs, CT drugs, biotherapy (BT) drugs, growth factors, home infusion costs, and cost of the MiCK assay. Average CT and BT drug costs were determined. We assumed high MiCK predictability for CT activity from solid tumor pilot studies and leukemia results. 4 models were evaluated: CT with a single active drug from MiCK for the duration actually given (ASC); CT with active drugs for the entire time (AC100); CT for 50% of the time period (AC 50) assuming a CT "holiday" for the other 50% of time; and CT with active drugs plus BT for 50% of the time (ACB 50). The costs in these 4 models were compared to actual claims payments.

Results:

196 PTs had CA during the 3.5 year period. 55 had CT. Total costs for CT were $5,647,165. Costs for IV CT drugs, SC drugs and drug admin were $1,149,404. Assuming the use only of active CT selected by MiCK assay, under model ASC average sav/PT was 85.3% of CT, SC and admin costs. Under model AC100, the average sav/PT were 26.0%. Under model ACB 50, the sav were 48.6%. In model AC 50, the sav were 62.7%. When the overall costs were evaluated, model ASC sav were 17.4%, model AC 100 5.3% , model ACB 50 9.9% and model AC 50 12.8%.

Conclusions:

PTP using the MiCK CS assay could save a high percentage of CT costs, and a substantial percentage of overall costs of CA care in an ASIC. Sav varied from 9.9% to 62.7% depending on effectiveness and duration of Rx, and necessity for continuing BT not testable by MiCK. The true value of PTP with MiCK could be higher, since use of active CT would increase quality of life and employment, and reduce disability and side effects.

http://www.asco.org/ASCOv2/Meetings/Abs ... ctID=30508