ESAs for Cancer-Related Anemia
Download
Report
Transcript ESAs for Cancer-Related Anemia
ESAs for CancerRelated Anemia
TMR Journal Club
Shuen Tan
October 6, 2009
Tonelli M, Hemmelgarn B, Reiman T, et
al. Benefits and harms of
erythropoiesis-stimulating agents for
anemia related to cancer: a metaanalysis. CMAJ 180(11): E62-71,
2009.
Anemia in Cancer
Related to cancer
Related to chemotherapy
Associated with:
quality of life
survival
ESAs: Benefit vs. Harm
Benefits
Improved QOL
Decreased
transfusions
? survival
Harm
Thromboembolism
HTN
Stimulate tumour
growth
(Cost)
? survival
Methods
Systematic review of ESAs for the
treatment of cancer-related anemia
Published and unpublished RCTs
Epoetin or darbepoetin vs. control
Adults age>18
Cancer-related anemia
>30 subjects in each group
English, French, Spanish, or Mandarin
“Any” Outcomes
Mortality
Cardiac events
Hospital admission
Quality of life
Hypertension
RBC transfusion
Adverse events
Subgroups
American Society of Clinical Oncology
criteria
Baseline hemoglobin
Chemotherapy (or not)
Target hemoglobin
Results
52 trials met criteria
4 trials in perioperative patients
30 trials in solid tumours
10 trials in hematologic cancer
11 trials included both
Mean duration 12 (2-28) weeks
Cardiovascular events
MI, stroke, CHF, revascularization
14 trials
RR 1.12 (0.83-1.5)
Hypertension
17 trials
RR 1.41 (0.94-2.12)
Tumour response
2 trials
No difference for complete response
• RR 0.88 (0.69-1.12)
No difference for partial response
• RR 0.70 (0.44-1.11)
Serious Adverse Events
21 trials
Increased risk in ESA groups
• RR1.16 (1.08-1.25)
Thrombotic events
13 trials
Increased risk in ESA groups
• RR 1.69 (1.27-2.24)
Sub-group analyses
No differences between any groups
and total study population
Do the American Society of Clinical
Oncology guidelines permit
identification of patients most likely to
benefit?
Validity
1. Did the authors ask a focused clinical
question?
For the most part, Yes
Well-defined patient group
Broad but reasonable disease
category
No specific outcomes stated
Included studies that “reported one or
more outcomes”
2. Were the criteria used to select articles
for inclusion appropriate?
Yes
Study type well-defined
Patients well-defined
Therapy well-defined
Outcomes not defined
Languages reasonably dealt with
Only 25/2025 studies could not be
assessed because of translation
3. Is it unlikely that important, relevant
studies were missed?
Yes
Very thorough search strategy
Multiple databases
ESAs extensively exploded
CancerLit?
Unpublished literature searched
Some papers included that were
published after search dates
3. Is it unlikely that important, relevant
studies were missed?
Very small percentage of citations
could not be retrieved (32/2025)
Abstracts screened by 2 reviewers
All flagged articles retrieved
Full text assessed by 2 reviewers for
inclusion
Disagreements resolved with a third
reviewer
4. Was the validity of the included studies
appraised (study quality)?
Yes
Chalmers index
More detailed version of the Jadad score
Randomization, blinding, and handling of
withdrawals
Rated statistical analysis, presentation of
results, and source of funding as well
Not entirely clear if the final rating was
subjective
Does not appear to have been incorporated
into the meta-analysis
5. Were assessments of studies
reproducible (data abstraction)?
Yes?
One reviewer abstracted data
A second reviewer checked for
accuracy
6. Were the results similar from study to
study (homogeneity)?
Yes
Random effects model
Quantified heterogeneity with the I2
statistic (=0% for all calculations)
Calculates proportion of total variation
in the estimates of treatment effects
that is due to heterogeneity between
studies
Issues related to the included studies
Overall, systematic review was well done
Limitations to applying results to patients
Short follow-up time (median 12 weeks)
Low-moderate quality scores
• Many had unblinded treatment groups
Majority were privately funded
Relevance
Will the results change my practice?
Are the outcomes important to my
patients?
Populations of Interest
Solid organ vs. hematologic cancer
Anemic (100 vs. 120) vs. very anemic
(<100)
Long-term (>12 weeks) vs. short-term
(<12 weeks) vs. really short-term (2-3
doses)
Chemo vs. no chemo
Shuen’s Thoughts -- Con
Increased reluctance to recommend use in
pre-op anemia
risk of thrombosis with surgical stress
response
Thoracic, bowel surgery not typically
associated with high blood loss
Lower targets, as few doses as possible
Anemia associated with survival, but does
treatment with ESA make a difference?
Shuen’s Thoughts -- Pro
Risk-benefit study of ESA vs. no ESA
but does not compare to other
treatments (e.g. transfusion)
Improved quality of life
? Uncertain diagnosis
Based on studies of low-moderate
quality
CancerCare’s Patients
Any changes in practice?
Is transfusion a “better” treament for
anemia than Epo?
Non-random oncologist #1
Following ASCO guidelines
Non-random oncologist #2
Rarely uses epo
Transfusion more common
Patients
Can a reasonable patient choose?
quality of life with survival
quality of life with survival
? quality of life with transfusion and ?
Survival
Cause of increased mortality unclear
Thromboembolism?
Tumour progression?
Something else?
Dose or duration-dependent?
Conclusion
The use of ESAs in cancer patients is
associated with increased mortality
and serious adverse events, but
improved quality of life and decreased
transfusions
The ASCO guidelines for the use of
ESAs do not appear to identify a
lower-risk, higher-benefit group
Conclusion
ESAs should be used cautiously in
any patient with a cancer diagnosis,
regardless of type of cancer,
chemotherapy, or degree of anemia
But are not contraindicated…
Questions?