For anti-cancer drugs, what is the health outcome benefit of a drug that improves progression free survival without an overall survival benefit and without a documented quality of life benefit?

Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.: For anti-cancer drugs, what is the health outcome benefit of a drug that improves progression free survival without an overall survival benefit and without a documented quality of life benefit?
Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.): yes
If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:: The effect on quality of life from the use of bevacizumab for the treatment of metastatic renal cell carcinoma v. no treatment with bevacizumab.
What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.): Patients with metastatic renal cell carcinoma
Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.): Patients who are candidates for bevacizumab.
Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.): Quality of life
Describe any health-related risks, side effects, or harms that you are concerned about.: According to the FDA posting, "Serious adverse events were reported in 31% of patients on the bevacizumab plus interferon arm and in 19% of patients on the interferon plus placebo arm. (bleeding, hypertension, proteinuria, and venous or arterial thrombosis.) Two patients with grade 5 bleeding events (ruptured aneurysm and hemoptysis), two patients with hypertensive encephalopathy, and four patients with grade 4 pulmonary embolism were reported in the bevacizumab plus interferon arm."

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

Cancer

AHRQ Priority Populations: None

Federal Health Care Program: None

Importance

Describe why this topic is important.

According to the FDA posting "On July 31, 2009 the U.S. Food and Drug Administration granted approval for the use of bevacizumab (Avastin, Genentech, Inc.) in combination with interferon alfa for the treatment of patients with metastatic renal cell carcinoma. The approval was based on results from the BO17705 trial which demonstrated a 5 month improvement in median progression-free survival(PFS)in bevacizumab-treated patients.

"The BO17705 trial did not demonstrate a statistically significant advantage in overall survival for bevacizumab plus interferon arm compared to interferon plus placebo treatment [HR 0.86 (95% CI: 0.72, 1.04), p= 0.13]."

Comment--In some studies the benefit "tail" may be long for a few patients even when the mean benefit is limited or none. This "tail" means that a few patients may benefit for a long time. There was no "tail" for bevacizumab for RCC.

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

I believe it is inappropriate for Medicare (CMS) to cover (and for the FDA to approve) a drug for the treatment of cancer that offers no overall survival benefit, or, failing that, no quality of life benefit. A PFS benefit only means the tumor growth does not progress for awhile but the patient does not live longer. While this benefit is promising, it is not sufficient for mainstream coverage or reimbursement compared to other services that potentially improve survivial or quality of life, or ease death through hospice. Payment for an expensive drug for a PFS only results in reduced access to care for other conditions due to lack of funds.

I think it is important for AHRQ to compare the value or benefit of no treatment vs. an anit-cancer intervention that provides only a PFS benefit.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

At a recent meeting of oncologists through the Association of Northern California Oncologist, the use of bevacizumab for the treatment of metastatic RCC was presented. The presenter stated interferon is very toxic so only 3% of candidates receive it. She lamented the study did not evaluate bevacizumab alone. Physicians at the meeting expressed concern there was no quality of life data which was needed to show the benefit of treatment in the absence of an OS benefit.

Also, interferon is not FDA approved for RCC treatment, and there is no evidence showing the effect of bevacizumab alone for RCC.

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

Lately, the threshold for coverage of an anti-cancer drug has been reduced to include PFS without an OS or QOL benefit. The controversy can been seen in ODAC's advice for avastin for breast cancer:

http://professional.cancerconsultants.com/news.aspx?id=40945

I am concerned about the trend to approve exensive anti-cancer threatments that do not offer a benefit for their primary indication, which is longer life. A secondary resonable benefit is improved quality of life. But PFS alone seems not a benefit.

Describe the timeframe in which an answer to your question is needed.

There is no rush. However, the public is concerned about government "rationing." I am concerned about rationing by CMS payment for health care of no value.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

Patients are faced with increasingly costly insurance premiumns, which, in part cover some anti-cancer drugs that offer little or no benefit to improve survival or QOL.Few decision makers are willing to designate non-coverage of an FDA approved product--meaning the FDA can cause insurance premiums to increase by approving a drug that is not effective. In my view, an anti-cancer drug is not effective when it offers no improved survival and no quality of life benefit.

Nominator Information

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