Inclusion Criteria

• Board-certified or eligible electrophysiologist
• In practice between 2 and 30 years
• Spends at least 75% of professional time in clinical practice
• Performs at least 10 ICD implants per month

Name

Hospital

State

Paul Gustafson

Park Plaza Hospital

TX

Thomas Cartwright

Ocala Regional Medical Center

FL

Michael Cashdollar

Chambersburg Hospital

PA

Wayne Keiser

Redwood Regional Medical Group

CA

Richard Caradonna

Florida Cancer Institute

FL

Michael Wertheim

Hematology/Oncology Associates of The Treasure Coast

FL

Michael Faig

North Ridge Medical Center

FL

Richard Locicero

Northeast Georgia Medical Center

GA

Simi Rai

The Reading Hospital and Medical Center

PA

Mayer Gorbaty

North Arundel Hospital

MD

Monica Mita

Cancer Therapy and Research Center

TX

Question

Pages

Q1: EPO Patients

Please describe the patient populations that you treat with EPO? How many patients on average in your practice at any one time are on EPO? What is your target Hb level? Has this changed materially in the past 3 months? If so, how?

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Q2: Hb levels - initiation, reduction, termination

For each of the patient populations on EPO please outline the Hb level at which you typically initiate EPO, the Hb level when you reduce your EPO dose and the Hb level when you stop dosing? Has this change materially in the past 3 months? If so, how?

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Q3: Dosing - starting , maintenance , highest

For these patient populations on EPO please outline your starting dose of EPO, your usual maintenance dose and the highest dose you would give? Has this changed in the last 3 months? If so, how?

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Q4: Initiation Hb

What percentage of your patients on EPO are being initiated above 12 g/dL? Above 12.5 g/dL? Above 13 g/dL? Above 13.5 g/dL? Has this changed in the last 3 months? If so, how?

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Q5: Treatment Hb

What percentage of your patients on EPO are being treated above 12 g/dL? Above 12.5 g/dL? Above 13 g/dL? Above 13.5 g/dL? Has this changed in the last 3 months? If so, how?

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Q6: Off-label use

How closely do you adhere to the labeled dosing and indications for EPO use?

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Q7: Perception of EPO products

Do you consider EPO products…

• Among the safest drugs you use
• Average in terms of safety among the drugs you use
• Among the riskiest drugs you use

Please explain your answer.

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Q8: Opinion of EPO

Has your opinion of the safety of EPO products changed in the past 3 months? Please explain why or why not.

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Q9: Perception of FDA alert

The FDA recently sent out an alert advising physicians about results from a large clinical trial evaluating EPO use in anemia patients not receiving chemotherapy, and a higher death rate in Aranesp-treated patients with no reduction in the need for transfusion compared to placebo. Specifically, the overall number of deaths was higher for patients receiving Aranesp in the study (48.5% vs. 46% for placebo, hazard ratio:1.29, p=0.006). Transfusion occurrences favored Aranesp but were not significantly different between the two groups (176 for Aranesp vs 215 for placebo, hazard ratio: 0.85, p=0.32)

• Are you aware of this alert?
• What is your perception of this alert?

How, if at all, have you changed (or would you change) how you use EPO, given this information?

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Q10: Perception of recent studies

Recent studies have suggested EPO products may cause harm:

• In January, Amgen announced in one of its clinical trials, patients getting Aranesp were more likely to die than those getting placebo (as noted above, patients not receiving chemotherapy)
• On 2/16, the Cancer Letter reported a Danish study of head and neck cancer was stopped early because the cancer seemed to recur more in patients being treated with Aranesp - Numerically the rate of locoregional failure (the study’s primary endpoint) was higher in the patients given Aranesp, compared to the patients not treated with the drug.

In February, the Journal of Clinical Oncology published an online paper describing a non-small-cell lung cancer trial in Canada was stopped early because those receiving Eprex were dying sooner – Median survival was 63 days for EPO vs 129 days for placebo in 70 patients (hazard ratio 1.84, p=0.04). Amgen has stated it strongly believes its drugs are safe and effective when used in approved populations consistent with label dosing recommendations. What do you think of these recent studies? Are these findings surprising to you, why or why not? How, if at all, have you changed (or would you change) how you use EPO, given this information?

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Q12: Perception of recent black-box warning and potential impact

More recently the FDA updated the labeling for EPO products with a black box warning applying specifically to the risks of off-label usage of EPO (increased risk of death and serious cardiovascular events when administering EPO to a target Hb >12 g/dL). The label also includes new dosing instructions which state that doctors should “maintain the lowest Hb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL”. Previous dosing instructions on the label indicated that a target hemoglobin level not to exceed 12 g/dL should be maintained, but did not explicitly indicate that patients should not fluctuate above 12 g/dL. What is your perception of the black box warning? What impact do you expect this recent warning and labeling change to have on your use of EPO?

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Q13: Reimbursement

What impacts have you seen on the reimbursement of EPO products? In February, the US Pharmacopeia dropped the use of Aranesp in some cancer patients. What do you expect the impact of this de-listing will be, and why?

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Q14: Expected trends in next 6-12 months

What do you expect the trends in use of EPO in oncology will be in the next 6-12 months, and why?

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Q15: Other issues

Other than what has been discussed, what other issues are important to consider for someone trying to understand the market dynamics of EPO use in oncology?

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Introduction

Welcome to this discussion among community-based oncologists. We will focus on the use of EPO and the impact recent data, FDA alerts, and new labeling has had and will likey have on your treatment practices. Panel Intelligence discussions are enhanced when you, as a panelist, not only respond to the posted questions, but also reply to comments made by our moderator and your fellow panelists. We look forward to a lively and interactive discussion. Please note: In your participation on this panel, Panel Intelligence expects and requires that you comply with the terms of the Consultant Confidentiality Agreement to which you previously agreed. If you have any questions about the terms of that agreement, please review them through the link provided on your Panel Intelligence home page after you've logged in.

Reading and posting instructions

Identifying Icons: Questions are marked with a . Important information is marked with a . Moderator questions are marked with . Supporting Documents are marked with .

Q1: EPO Patients

Please describe the patient populations that you treat with EPO? How many patients on average in your practice at any one time are on EPO? What is your target Hb level? Has this changed materially in the past 3 months? If so, how?

Panelist 9: We treat probably hundreds of patients per week with epo agents. We treat chemo induced anemia/MDS/CRFand used to treat anemia of cancer until just recently. After last week's data, we no longer give any eqofor Hgb of 12.

Panelist 5: I treat patients with anemia of chronic disease, chemotherapy induced anemia,cancer induced anemia,and MDS patients. I am treating typically 100 patients on EPO therapy. My target has been 12gm Hgb/this has not changed recently except when dictated lower by insurance co.

Panelist 1: pts are those with solid tumors, some NHL usually with chemo induced anemia. 15-20 per month. target Hgb 12. EPO usage has dropped 20% primarily in pts treated primarily due to Amgen, ASCO and FDA warnings.

Panelist 6: I treat mds, chemo related anemia, renal failure anemia. At any one time about 40-50 patients are one epo. Target Hgb level is generally 12 and has not changed in the past three months.

Panelist 8: Patients on chemotherapy, one one year from completion of chemtherapy, myeldysplasia, renal failure with hemoglobinn less than 11.9 if symptomatic or otherwise hemoglobib 10 or less

Panelist 8: In further response, over 400 patients on epo. our Medicare allowed treatment to 13. With new FDA black box warning, HG of 12 is now target.

Panelist 7: CIA, MDS, anemia of chronic disease (polyneuropathies), not much anemia of cancer (did use this code to continue to rx those patients who had prolonged anemia after chemo). 50-100 patients on epo at any given time. Hgb target 12, strict guideline. No real change in last 3 months other that the anemia of cancer recently, drop maybe 5 %

Panelist 4: I treat 2 common groups: anemia due to chemotherapy and anemia due to renal insufficiency. I estimate more than 50 patients are on EPO. The target hgb is 12. None of this has changed in the last 3 months.

Panelist 10: I treat primarily chemo induced anemia- probably have about twenty of them. My target hgb goal is 12. In addition I treat nonmalignant anemia secondary to epo deficiency e.g. anemia of renal insufficiency and anemia of chronic diseases e.g. diabetes and CHF. I have about 10 of these patients. This hasn't changed recently

Panelist 3: I probably treat over 100 patients at any one time with ESAs, mainly Aranesp. I treat mostly chemotherapy induced anemia but also some MDS, renal failure and occasion AoC. The target Hgb is 12 and has not changed. I am no longer treating AoC.

Follow-up ALL: Changes

Most report no change in Hb targets in the past 3 months. When was the last change in targets, and what was this change?

Panelist 5: I have not changed my targets/I have always targeted a Hb of 12g with cessation of therapy at that time.

Panelist 1: A target Hgb of 12 has been the std for some time now. Ortho and amgen use the target of 12. For the NCCN it is 11-12.

Panelist 3: The target has been a hgb of 12 for at least 10 years or more

Panelist 9: Target remains 12 but will now give additional at 12 to maintain it there now

Panelist 6: Have not had any change in targets in many years.

Panelist 4: I reset the target to 12 after the NEJM report of increased cardiac mortality in HD patients on EPO. That was well over a year ago.

Panelist 8: with the black box warning now 12 instead of 13

Panelist 10: My target has been 12 for as long as I can remember

Panelist 2: We have always used 12 as the target and there has been no recent change.

Panelist 7: when amgen introduced the 500s

Follow-up ALL: Insurance

A few panelists note the target is 12, unless dictated by insurance companies. Are others experiencing greater restrictions by insurance companies? Please discuss when insurers began to change their policies, quantify (if possible) the impact stricter insurance guidelines is having on your EPO usage, and discuss if you expect this will increase in the near future.

Panelist 5: In the past 2-3 months some insuance groups are insisting on starting EPO therapy only when the Hb is below 10g. Before we had the liberty of starting with a Hb below 11g. This has reduced EPO usage by @10%. I anticipate tighter rules for usage of EPO agents in the future.

Panelist 1: The target is 12 for ortho and for amgen. For the NCCN it is 11-12. Carriers will not reimburse beyond 12.

Panelist 3: I have not noticed any tighter restrictions by insurance companies.

Panelist 9: Have always followed Medicare guidelines

Panelist 6: so far have not noted any change by insurance companies, but I expect in the near future there will be more strict usage of the target of 12 and a cbc may have to be included with the bill.

Panelist 4: Insurance companies have not been an issue for me. However, just this week, I got a message from my practice administrator that hgb levels will now be required by United.

Panelist 8: not at this time. Some mandate procrit over aranesp as it is cheaper

Panelist 10: united is now requiring that the hematocrit be attached to your claim. This is effective April 1.

Panelist 2: We have not seen any recent changes.

Panelist 7: only united asking for hgb and hct. no material change in useage

Panelist 2: Most pts on epo are also getting chemo and have marrow suppression secondary to that. Other pts include mds, anemis secondary to other etiologies like renal insuff etc. We have a large practice and at one time we have about 1000 pts on Epo. Our target is 11gm and above. It has not changed recently.

Panelist 11: Chemotherapy induced anemia around 40-50 per month. Target Hb 12; no changes over the last months.

Panelist 11: I have the same target for Hb 12 according to the NCCN/ASCO guidelines; no changes.

Panelist 11: I have not experienced any restriction from the insurance companies for the moment.

Q2: Hb levels - initiation, reduction, termination

For each of the patient populations on EPO please outline the Hb level at which you typically initiate EPO, the Hb level when you reduce your EPO dose and the Hb level when you stop dosing? Has this change materially in the past 3 months? If so, how?

Panelist 9: We start tratment for a Hgb of less than 11 grams. We reduce for a 1 gram rise within 2 weeks and stop at 12. Since the data last week, we still do the same for now, however, I feel less aggressive in treating asymptomatic patients with Hgb's in the 10-11 range

Panelist 5: Start therapy when the Hgb goes below 11gm.Will reduce dose if the patient demonstrates slow and steady improvement. Will DC EPO when I obtain Hgb of 12gm.

Panelist 1: EPO initiation Hgb less than 11 after chemo.I have elimininated primary prophylaxis in Ca pts with Hgb less than 11, waiting for Hgb response to chemo and then starting-Hgb is usually less than 10 at that point. If Hgb approaches 12 or if Hgb rises more than 1 gm in 2 wks I will reduce dose by 25%.If Hgb exceeds 12 I stop dosing ands follow. No change in this practice.

Panelist 6: I generally initiate epo below hgb ll, depending on symptomatology; I reduce the dose above 12 and hold at 13. Generally lowering the target for renal to 12 over the past 1-2 months.

Panelist 8: HG 11.9 or less if symptomatic; otherwise in 10 range. Epo stopped once HG reaches 12 in view of recent black box warning. Previously, our Medicare intermediary allowed treatment to HG of 13.

Panelist 7: start at less than 11 for most patients, some ins cos require < 10.5 . Keep full dose until 12, then try to adjust interval rather than dose. We get fewer injection charges, but easier on the patients. No change

Panelist 4: I initiate EPO when hgb falls below 11.0; then continue it until hgb is > 12. I generally start at a convenient interval based on chemotherapy scheduled (500 q3w or 300 q1-2w for Aranesp; 40K units q week for procrit). I rarely change the dose, I usually just hold the dose if the hgb > 12. This practice has not changed over the last 3 months.

Panelist 10: I initiate usually at 11, reduce at 12 and stop at 13

Panelist 3: Generally start around 10 depending on symptoms. Reduce with a 2 gram rise and stop at 12. Now I am less aggressive in starting at a Hgb of 12.

Follow-up Panelists 5 and 3

Please indicate if your start, reduce, and stop targets have changed materially in the past 3 months. Thank you.

Panelist 5: As noted above ,recently restricted by some insurance groups to start at a lower hb/ 10g vs. the previous 11g level. My reduce targets and stop targets are the same.

Panelist 3: No changes

Panelist 1: start Hgb less than 11. Stop Hgb 12

Panelist 10: I have adjusted all three downward. What I do now is that when a hgb comes back e.g. 11 I will repeat in 1-2 weeks. Until now I would just start the procrit but I am more reluctant to do so.

Panelist 2: It has not changed recently - We start epo below 11 and stop at 12

Panelist 7: no change

Panelist 2: we usually start at 10 gm or lower and stop treatment when iy goes above 12 gm. we start at 40000 units and increase to 60000 if no significant response in 1 mnth. we may then reduce it to 40000 if hb is continually above 12 gm with 60000 and it has notchanged over the last few mnths.

Panelist 11: I start around 10 (depending on symptoms); stop at 12; and reduce is 1 gr increase in 2 weeks.

Q3: Dosing - starting , maintenance , highest

For these patient populations on EPO please outline your starting dose of EPO, your usual maintenance dose and the highest dose you would give? Has this changed in the last 3 months? If so, how?

Panelist 9: We start at different doses depending upon the indication and Hgb level. For CRF, we start at 60-100mcg's Q2w. For anemia seconday to chemo and MDS we usually start at 200mcg Q2w and escalate up to 4.5mcg/kg qw if needed. This has not changed recently.

Panelist 5: Depending on severity of anemia and body mass of patient will start at Aranesp 300mcg q2wks,will increase to 500mcg dose if needed. Sometimes start with a weekly loading dose for 2-3 weeks.

Panelist 1: For CIA I usually start with aranesp at 500 mcg q 3 wk. This is highest dose. If Hgb exceeds 12 I will dose reduce as stated before or just reduce to 300 mcg q 3 wk. No change.

Panelist 6: starting dose for all patients is generally 40000 procrit weekly or aranesp 200 q 2 weeks; will raise to 60000 weekly or 300 q 2 weeks if suboptimal response, occ. in mds will go to 80000 procrit weekly. No changes in the past 3 months.

Panelist 8: Aranesp started at 60 for renal failure q 2 week and 200mg for chemotherapy induced anemia. Maintenance dose depends on specific paient, any where from 200 to 400mg of aranesp with attemt to maintain Heoblobin in 11.5 to 11.9 range. Highest dose is 500mg.

Panelist 7: Aranesp 500 q 3 weeks, or wgt based dosing protocol. Highest dose as allowed by wgt. no change

Panelist 4: Dosing is as a decribed in previous question. Max dose for Aranesp is 500; 60K for Procrit. This practice has not changed.

Panelist 10: I start at procrit 40k/wk. after 4 weeks if response is poor i increase to 60/wk. If response is still poor the most I give is 90/ wk. The usual maintenance is 40/wk. This is for my chemo patients. For the renal patients I start at 20/wk and adjust according to response. The typical maintenance dose in these patients is 20 every other week.

Follow-up Panelists 5, 8, 10

The other panelists report no material change in the initiation, reduction, and maintenance doses; do you agree or disagree?

Panelist 5: Start doses now may be higher due to demands for a lower hg to start. Reduction and maintance doses are the same.

Panelist 8: No. medicare is now mandated lowering the dose as the HB rises from 11 to 12 in an attempt to maintain a "steady state" between 11.5 and 12

Panelist 1: agree

Panelist 10: Just minor change. I now wait two weeks to recheck before commencing.

Panelist 2: Agree. No change

Panelist 7: agree

Panelist 3: Aranesp 200 to 300 mcg q2w or 500 q3w. This hasn't changed.

Follow-up ALL: Any changes

Most of you indicate no change in dosing patterns over the past 3 months. When was the last time you changed your dosing patterns, and what prompted this change?

Panelist 5: No significant dosing changes with the exception of possible higher initiating doses when I am required to start at a lower Hg target.

Panelist 1: I personally have not seen any AEs.Black box warnings state to use the lowest effective dose to gradually reach the target. We will have to follow these guidelines. This would be 150 mcg q wk, 200 mcg q 2 wk, or 300 mcg q 3 wks. we will hold on the 500cg dose q 3 wk

Panelist 3: Only recent change was occasionally using q3w Aranesp dosing. However this happened over a year ago

Panelist 9: No significant change in dosing patterns yet. However, I am not quite as aggressive in treating anemia as I was. I try to insure that pts don't go over 12 grams at all.

Panelist 6: Have not changed dosing patterns in many years.

Panelist 4: When the Aranesp 500 mcg dose became available and marketing for the q3w schedule began, I started using that regimen when it was practical (chemo regimen synchronization).

Panelist 8: the fda black box warning

Panelist 10: Before now it was years ago

Panelist 2: We have not made any changes recently.

Panelist 7: when aranesp came out in 500s

Panelist 2: We start at 40000 units of Procrit and increase to 60000 if response is suboptimal but never above that. rarely we use Aranesp which we start at 200 and increase to 300 q 2 weekly or change it to weekly schedule. No change in last 3 mnths.

Panelist 11: Start with 200 q 2 weeks or 300 q 3 weeks Aranesp, increase to 300-500 (max)q 2 weeks, depending on the results. No changes.

Panelist 11: No change except 300 q 3weeks.

Q4: Initiation Hb

What percentage of your patients on EPO are being initiated above 12 g/dL? Above 12.5 g/dL? Above 13 g/dL? Above 13.5 g/dL? Has this changed in the last 3 months? If so, how?

Panelist 9: None and this has not changed

Panelist 5: NONE. No indication for EPO above 12gm

Panelist 1: For pts with CIA at those levels I am not giving aranesp. No change.

Panelist 6: No patients initiated above 12 and no change.

Panelist 8: None. No change in this policy

Panelist 7: NO patients have ever been initiated above 12. No ins coverage for this where we are. Therefore no change

Panelist 4: 0%; no change.