Effects of Funding Policy Changes and Health Warnings on the Use of Erythropoiesis-Stimulating Agents [Original Contributions]

Effects of Funding Policy Changes and Health Warnings on the Use of Erythropoiesis-Stimulating Agents [Original Contributions]

Purpose:
To characterize the effects of formulary changes and governmental safety warnings on use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.

Patients and Methods:
We conducted a cross-sectional time-series analysis using health administrative data from Ontario, Canada. From January 1997 to December 2009 we identified all ESA initiations among patients diagnosed with cancer. We explored the effects of two formulary changes that progressively liberalized coverage for ESAs, first by rescinding the requirement for blood transfusion in 2003 and then by removing all restrictions in 2007. We also explored the effect of US Food and Drug Administration and Health Canada warnings issued in the second quarter of 2007. To assess regional variability in ESA use, we determined prescription rates for each of Ontario's 14 regional cancer centers.

Results:
After the first formulary change, the ESA initiation rate increased to 1.66 new users per 1,000 patients with cancer, 374% more than predicted (P < .001). After the second formulary change, the initiation rate increased to 3.97 new users per 1,000 patients with cancer, 73% more than predicted (P < .001). After the safety warnings, this rate declined 81% by study end (P < .001). We found significant regional variation in ESA use.

Conclusion:
Formulary access and safety warnings had significant impacts on the new use of ESA drugs in patients with cancer. This suggests that both are effective means of influencing the use of these drugs. Variable ESA prescription rates across our region may reflect a lack of consensus regarding their utility.

paywalled: Guideline-Based Peer-to-Peer Consultation Optimizes Pegfilgrastim Use With No Adverse Clinical Consequences [Original Contributions]

Guideline-Based Peer-to-Peer Consultation Optimizes Pegfilgrastim Use With No Adverse Clinical Consequences [Original Contributions]:

Purpose:
Practice guidelines do not recommend the routine use of colony-stimulating factors when there is a low risk (< 10%) of febrile neutropenia (FN). We prospectively determined whether expert peer-to-peer consultation with prescribing oncologists would improve adherence to guidelines and whether there would be any adverse events associated with that adherence.

Methods:
Commencing in March 2010, we reviewed requests for pegfilgrastim from 22 community oncology practices comprising 78 physicians providing service to approximately 97,000 Medicare members. Paid claims data on all chemotherapy and supportive care medications were reviewed from fourth quarter (Q4) 2009 through third quarter (Q3) 2010. In total, 82 patients received pegfilgrastim. If the prescribed chemotherapy was associated with a low risk (< 10%) for FN, then a peer review was initiated. The treating physician made the final decision to use, or not use, pegfilgrastim, and no denials were issued.

Results:
A total of 245 units (1 unit = 6 mg) of pegfilgrastim were administered during the four quarters analyzed. Use in the low-risk category decreased from 52 units in Q4 2009 to 15 units in Q3 2010. The per-member per-month (PMPM) cost of pegfilgrastim decreased across quarters, with an average cost of $1.07 PMPM for Q4 2009 and $0.57 PMPM for Q3 2010. No studied patient was admitted for neutropenic fever.

Conclusion:
Active expert peer-to-peer consultation with prescribing oncologists can promote adherence to guidelines and potentially lead to significant cost reductions without significant risk of neutropenic fever, with or without hospitalization, for patients with cancer.

Healthnewsreviews blog: The marketing of anemia drugs - a story we shouldn't forget (including comments)

The marketing of anemia drugs - a story we shouldn't forget

 "In an opinion piece on TheScientist.com, Daniel W. Coyne writes, “Amgen’s incomplete report on an early major trial of epoetin misled the medical community about the anemia drug’s risks and benefits—and helped make Amgen rich.”
In the book, “How We Do Harm,” Otis Brawley, MD, chief medical and scientific officer of the American Cancer Society, writes quite a bit about hemoglobin-building drugs.  He discusses:.....

paywalled: Treatment of Chemotherapy-Induced Anemia in Ovarian Cancer Patients: Does the Use of Erythropoiesis-Stimulating Agents Worsen Survival?

Treatment of Chemotherapy-Induced Anemia in Ovarian Cancer P... : International Journal of Gynecological Cancer

Abstract

Objective: 

Considering the paucity of data relating erythropoiesis-stimulating agent (ESA) use to ovarian cancer survival, our objective was to evaluate the effect of ESA as used for the treatment of chemotherapy-induced anemia (CIA) on survival in ovarian cancer patients.

Materials and Methods:  

A multi-institution retrospective chart review was performed on ovarian cancer patients. Data collection included patient demographic, surgicopathologic, chemotherapy, ESA, and survival data. Patients were stratified by ever-use of ESA and were compared using appropriate statistical methods.

Results: A total of 581 patients were eligible for analysis with 39% (n = 229) patients with ever-use of ESA (ESA-YES) and 61% (n = 352) never-use ESA (ESA-NO). Mean age was 60.4 years with most patients having stage IIIC (60%) of papillary serous histological diagnosis (64%) with an optimal cytoreduction (67%). Median follow-up for the cohort was 27 months. Both ESA-YES and ESA-NO groups were similar regarding age, body mass index, race, stage, histological diagnosis, and debulking status. Compared with the ESA-NO group, ESA-YES patients were significantly more likely to experience recurrence (56% vs 80%, P < 0.001) and death (46% vs 59%, P = 0.002). Kaplan-Meier curves demonstrated a significant reduction in progression-free survival for ESA-YES patients (16 vs 24 months, P < 0.001); however, overall survival was statistically similar between the 2 groups (38 vs 46 months, P = 0.10). When stratifying by ever experiencing a CIA, ESA-YES patients demonstrated a significantly worse progression-free survival (17 vs 24 months, P = 0.02) and overall survival (37 vs 146 months, P < 0.001).

Conclusions: 

Our data evaluating the use of ESA as a treatment of CIA in ovarian cancer patients are similar to reports in other tumor sites. Considering that patients who used ESA were more likely to experience recurrence and death and to have decreased survival, the use of ESA in ovarian cancer patients should be limited.

Prevalence and management of cancer-related anaemia, iron deficiency and the specific role of i.v. iron

Prevalence and management of cancer-related anaemia, iron deficiency and the specific role of i.v. iron

Background: Chronic diseases reduce the availability of iron for effective erythropoiesis. This review summarises clinical consequences of iron deficiency (ID) and anaemia in cancer patients, mechanisms how impaired iron homeostasis affects diagnosis and treatment of ID, and data from clinical trials evaluating i.v. iron with or without concomitant erythropoiesis-stimulating agents (ESAs).......

Blogger's Note: table includes solid tumors

Table 1.

Reported prevalence of iron deficiency in different cancer patient populations

"potential role for i.v. iron as first-line therapy for CIA?

Guidelines recommend treatment of underlying causes of anaemia such as ID before initiation of an ESA. However, studies examining i.v. iron as sole anaemia treatment in cancer patients are only just starting to emerge. Two relevant small (N = 44 and 75 patients), controlled, randomised clinical trials have been published. Both studies involved patients with gynaecologic cancers receiving chemotherapy or radiochemotherapy, and in both, i.v. iron supplementation significantly reduced the number of required blood transfusions [15, 16]. In one study, significantly higher Hb levels were observed in the i.v. iron compared with the oral iron group at the end of the study period, although mean Hb levels included data from patients who received transfusions as well as those who did not [15]. The other study, comparing i.v. iron versus no anaemia treatment, achieved a lower rate in transfusions despite a higher baseline proportion of anaemic patients in the study group [16]. Both studies missed to assess iron status parameters such as TSAT and serum ferritin; thus, the proportion of patients with either functional or absolute ID could not be determined."

cross references:

1. 15.↵
   1. Dangsuwan P,
   2. Manchana T

   . Blood transfusion reduction with intravenous iron in gynecologic cancer patients receiving chemotherapy. Gynecol Oncol 2010;116:522-525.

   CrossRefMedline

   1. 16.↵
      1. Kim YT,
      2. Kim SW,
      3. Yoon BS,
      4. et al

      . Effect of intravenously administered iron sucrose on the prevention of anemia in the cervical cancer patients treated with concurrent chemoradiotherapy. Gynecol Oncol 2007;105:199-204.

      CrossRefMedline

       Concluding remarks

      The high prevalence of ID and anaemia in cancer patients suggests that these complications may need more attention in clinical practice. Current guidelines for treating anaemic cancer patients recommend that ID should be considered as underlying cause of anaemia before initiating ESA treatment and acknowledge that i.v. iron supplementation is superior to oral iron. .....................Published randomised controlled trials show that i.v. iron enhances response rates to ESA therapy and may be effective in reducing ESA doses and blood transfusion requirements, even if long-term safety remains to be examined. Available early reports on the use of i.v. iron as first-line anaemia therapy suggest that some patients could benefit from i.v. iron even without concomitant ESA. However, larger randomised controlled studies with long-term follow-up are necessary to confirm long-term efficacy and safety.

abstract: Comparative cost efficiency across the European G5 countries of originators and a biosimilar erythropoiesis-stimulating agent to manage chemotherapy-induced anemia in patients with cancer

Comparative cost efficiency across the European G5 countries of originators and a biosimilar erythropoiesis-stimulating agent to manage chemotherapy-induced anemia in patients with cancer

Conclusion: Managing chemotherapy-induced anemia with biosimilar epoetin α is consistently cost efficient over treatment with originator epoetin α, epoetin β, and darbepoetin α under both fixed and weight-based dosing scenarios.

JCO: Are Hematopoietic Colony-Stimulating Factors Over- or Underused?

Are Hematopoietic Colony-Stimulating Factors
Over- or Underused?

"Since their introduction, there has been debate about the benefits,
risks, and costs of hematopoietic colony-stimulating factors
(CSFs). We suggest that the use of CSFs to allow dose maintenance of
chemotherapy for common metastatic solid tumors is unsupported
by evidence, and we should reconsider using a $3,500-per-cycle injection
for a supportive care drug without major benefit......."

Comments and Controversies -

  A Way Forward on the Medically Appropriate Use of White Cell Growth Factors

 JCO published online on February 27, 2012; DOI:10.1200/JCO.2011.39.9980.

[PDF]

Table 1. Comparison of Major Guidelines 

 

How Did We Arrive at Widespread Use Without
Clinical Trial Justification?

 

The Way Forward to Evidence-Based Use of CSFs

"Increased concern about escalating costs 46-48 should cause us to
examine each component of current care. Oncology professional societies have demanded some demonstrable improvement in an important outcome before adoption of a new technology.49 The lack of
proven benefit from CSFs in support of therapy in common advanced
solid tumors, the high cost, the disparate US and world use patterns
with no difference in mortality, 50 and the potential for or appearance
of economic self-interest should give the oncology community pause.
There are concrete steps the US oncology community can take to
foster more evidence-based care. The Quality Oncology Practice Initiative 51 could add overuse as a quality criterion 52 and report CSF use in palliative-intent regimens when there is less than a 20% risk of FN. The major guideline groups (European Organisation for Research and Treatment of Cancer,6 National Comprehensive Cancer Network,5
and ASCO4) should endorse dose modification as an equally appropriate and preferred strategy in the absence of proven benefit."

 

 

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours

Randomized Phase 2 Dose-finding Study of Weekly Administration of Darbepoetin Alfa in Anemic Patients with Lung or Ovarian Cancer Receiving Multicycle Platinum-containing Chemotherapy

ACS :: Possible Risks of Blood Product Transfusions

Comment: Before Erythropoiesis-stimulating agents were introduced, blood transfusions were widely used for the improvement of platelet counts etc. With recent negative research regarding Erythropoiesis-stimulating agents, blood transfusions will be a choice - seek professional/oncologist opinion. This article from the ACS describes some of the concerns with blood transfusions.