This presentation aims at providing the oncologists with a well-organized, inclusive and updated evidence of the benefit of adding taxanes in the adjuvant settings of breast cancer. It will answer some questions like, what are the indications of adding taxanes for those patients, and which regimen is best to chose. It is directed mainly to clinical Oncologists, Medical Oncologists, Oncology residents and medical students who are interested in breast cancere.

1. The Magnitude of Benefit from
Adding Taxanes to Anthracyclines in
the Adjuvant Settings of Breast
Cancer:
Discussion of Large Trials and Meta­analyses
By
Osama Elzaafarany
Medical Oncologist
Alex. University. Egypt.
October 2018

2. Introduction
➢ Her2/neu is over-expressed in 25 -30 % of patients,
and those patients will get significant benefit from
Trastuzumab + chemotherapy in the adjuvant settings.
➢ How about those who did not over-express Her2/neu
( ≈ 70 %), how to achieve the best care for them in the
adjuvant settings ?

3. Questions to answer:
● What is the magnitude of benefit from adding
taxanes in terms of DFS and OS?
● Which patient will get the best benefit from
adding taxanes in their adjuvant treatment?
● Which taxanes’ regimen should we use?

4. First Question:
What is the magnitude of benefit from adding taxanes in
terms of DFS and OS?

5. Four trials showed OS benefit
CALGB
9344
BCIRG-
001
PACS-01 AGO
Regimen AC – P (3Ws)
Vs
4 X AC
TAC X6
Vs
FAC X6
FEC X 3 – D X3
Vs
FEC X 6
EC X4 – D X4
Vs
FEC X 6
5 ys DFS
(Absolute benefit)
5 % 7 % 5 % 2.5 %
5 ys OS
(Absolute benefit)
3 % 6 % 4 % 1.7 %
10 ys OS
8 %
+ve LNs

6. Three trials showed DFS benefit only
NSABP-B28 GEICAM-9906 GEICAM-9805
Regimen
AC – P
(P: 225 mg/m2
)
Vs: AC X4
FEC X4 – P X 8 Ws
Vs:
6 X FEC
TAC X 6
Vs:
FAC X 6
5 ys DFS
(absolute benefit)
4 % 6.4 % 4.8 %
High-risk node
negative
+ve LNs+ve LNs

7. Negative Taxanes Trials
E 2197
Intergroup trial
-MA 21 -UK TACT
Regimen 4 X AT
Doce: 60 mg/m2
Vs:
4 X AC
3 arms:
AC – P
DD-EC X6 – D X4
Vs:
CEF X 6
FEC X4 – D X4
Vs:
FEC X 8
Negative nodes
Included
Negative nodes
Included

8. Three Meta-analyses
Cochrane
2007
Italian
2008
EBCTCG
2012
Number of Trials 21,000 22,900 100,000
Number of Patients 12 13 123
Absolute OS benefit 5-years
5 %
5-years
3 %
8-years
3.2 %
Subgroup who
benefit ?
No benefit in
ER +ve
4 or more + LNs
All subgroups

9. 8­years OS in the EBCTCG 2012

10. Second Question:
Which patient will get the best benefit from adding
taxanes in their adjuvant treatment?

11. Those patients should be considered for adding
taxanes to anthracyclines in the adjuvant treatmnet:
● Based on phase-III trials:
– Node positive.
– High-risk node negative:
➢ Age < 30 ys.
➢ T > 2 cm.
➢ ER-negative.
➢ Grade II-III.
● Based on meta-analyses:
– All patients’ subgroups.

12. Third Question:
Which taxanes’ regimen should we use?

13. Options / Questions
1) AC-P vs TC regimen.
2) AC-P vs TAC regimen.
3) Dose-dense taxanes regimens.
Whats is the evidence?

14. AC-P vs TC regimen
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15. Her2 negative
TC X 6
standard AC and taxane
combination regimens:
i.e. TAC, AC-P.
● 2100 pts in each gp.
● Median FU 3.3 ys.
● 1ry end point: IDFS
Joint Analysis of the Anthracyclines in Early Breast Cancer (ABC) Trials
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16. Joint Analysis of the Anthracyclines in Early Breast Cancer (ABC) Trials
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17. Joint Analysis of the Anthracyclines in Early Breast Cancer (ABC) Trials
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18. ● This question was answered by the EBCTCG meta-
analysis which was published as an abstract in the San
Antonio Breast Cancer Symposium 2017.
● It examined the effect of sequential versus concurrent
anthracycline and taxane-based chemotherapy in 11,500
women enrolled in nine trials.
● Sequential regimens (eg, AC - P) was associated with
improvement in disease recurrence rates and OS
compared with concurrent regimens (eg, TAC).
● AC-P is better than TAC.
AC-P vs TAC regimen
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19. ● There are two important meta-analyses which examined this
issue:
● The first was published in the NCI journal in 2010 and
showed that Dose-dense chemotherapy results in better
overall and disease-free survival, particularly in women with
hormone receptor-negative breast cancer.
● The second is the previous EBCTCG in 2017 as abstract and
showed significant reduction in recurrence rate in both ER
+ve and -ve patients, and better OS.
● Also, the second meta-analysis showed that DD-chemo was
not associated with increased treatment-related toxicity.
Dose-dense taxanes regimens
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20. To answer the best regimen question:
● Based on these data, the best regimen to
consider for Her2 -ve patients is dose-dense
AC-P, followed by AC-P/3Ws then TAC.
1) DD AC-P.
2) AC-P / 3Ws.
3) TAC.

21. ● Non-anthracycline regimens (eg. TC X4 and CMF
X6) should be offered to those patients with one of the
following:
1) Low risk patients:
● Negative nodes + ER positive
● Negative nodes + ER -ve + T < 1 cm
2) History of cardiac failure and other cardiac issues
3) Patients refuse the anthracyclines risk, specially the
leukemia risk.
● Non-taxanes regimens should be considered when
there is peripheral neuropathy and contra-indications
for corticosteroids.

22. Conclusion
(Answers to our questions)
‫ــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ‬
● What is the magnitude of benefit from adding taxanes in
terms of DFS and OS?
Modest but significant OS benefit, which does nit
exceed 8 % over 10 years.
● Which patient will get the best benefit from adding
taxanes in their adjuvant treatment?
All patients’ subgroups
● Which taxanes’ regimen should we use?
DD-AC-P, then AC-P/3Ws, then TAC.