Taxane chemotherapy has been shown to improve outcomes for patients with breast cancer when added to standard anthracycline-based regimens either sequentially or concurrently in both the adjuvant and neoadjuvant settings. Several large clinical trials demonstrated that the addition of paclitaxel or docetaxel to doxorubicin and cyclophosphamide (AC) chemotherapy resulted in significant improvements in disease-free survival and overall survival rates compared to AC alone. Higher pathologic complete response rates were also observed with the incorporation of taxanes. Dose-dense regimens with shorter intervals between cycles further improved outcomes over conventionally dosed chemotherapy.

1. TAXANE CHEMOTHERAPY IN CA BREAST

2. Development of Chemotherapy
Breast Cancer
• Before anthracyclines
– CMF, CMFVP
• With anthracyclines
– Combinations: AC, FAC, AVCMF, FEC, CEF
– Sequence and Alternating (Milan A & B)
– Dose intensity,dose density, HDCT
• Taxanes (Paclitaxel/Docetaxel)
– Sequential: A T C or AC T
– Combinations: TA, TAC
• Biologic Modifiers (Herceptin)
– Integration in chemotherapy strategies
1970s
1980s
1990s
2000s

3. first report on adjuvant taxane
therapy
• The CALGB 9344 study
• n= 3121 women
• Age=>65
node-positive breast cancer
• four cycles of AC or four cycles of AC followed by four cycles
of paclitaxel (AC-T) with dose-escalated doxorubicin

8. • The addition of paclitaxel was associated with significant
5-year DFS (70% versus 65%)
OS (80% versus 77%)
• no benefit observed with dose escalation of doxorubicin
beyond 60 mg/m2/dose.
• Addition of taxane showed more benefit in hormone recptor
negative patients

9. • In a retrospective study of 1,500 pts on
• CALGB 9344, the benefit of taxol appeared to
be in HER2+ tumors
• not In HER2–/ER+ tumors

10. NSABP B-28 trial
• 3060 patients
• .

11. a median follow-up of 64.6 month

12. • Taxane improved DFS , but not os.

13. DOCETAXEL
• The efficacy of adjuvant docetaxel has also been evaluated in
several clinical trials.
• The BCIRG 001 study
• randomized 1491 women with axillary node-positive breast
cancer
• 1. six cycles of (TAC)
• 2. six cycles of (FAC) as adjuvant chemotherapy

16. • With a median follow-up of 55 months
• estimated DFS at 5 years was 75% for patients
receiving TAC 68% for those receiving FAC,
• representing a 28% reduction in the risk of
relapse in the TAC group.
• overall survival at 5 years were 87% for TAC and
81% for FAC
• representing a 30% reduction in the risk of
death with TAC

17. • Grade 3 or 4 neutropenia, febrile
neutropenia, and grade 3 or 4 infections were
significantly higher in the TAC group
• but no deaths occurred as a result of infection

18. 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
Hazard Ratio
TAC Better FAC Better
10+
4-9
1-3
All
Number of Positive Nodes
(N=149)
(N=420)
(N=922)
(N=1491)
BCIRG001 - DFS: Comparison by Nodal Status
Original Analysis: 1-3 versus 4+ Nodes
DFS Relative Risk Reduction by Nodal Status

19. Disease Free Survival by Hormonal Status
TAC
FAC
0 12 24 36 48
Months
N at Risk
TAC
FAC
231 217 188 47 0
228 202 158 34 0
50
60
70
80
90
100
%AliveandDiseaseFree
TAC
FAC
0 12 24 36 48
Months
N at Risk
TAC
FAC
514 493 466 105 1
518 497 447 116 0
50
60
70
80
90
100
Negative Positive
RR = 0.62
p = 0.005
RR = 0.68
p = 0.02
Nabholtz et al, ASCO 2002 (Abs 141)
BCIRG 001

20. TAC
FAC
0 12 24 36 48
Months
N at Risk
TAC
FAC
485 467 433 102 1
478 455 402 108 0
40
50
60
70
80
90
100
%AliveandDiseaseFree
TAC
FAC
0 12 24 36 48
Months
N at Risk
TAC
FAC
138 131 118 32 0
148 135 107 26 0
40
50
60
70
80
90
100
Disease Free Survival by HER2 status
Negative (FISH) Positive (FISH)
RR = 0.74
p = 0.06
RR = 0.59
p = 0.02
Nabholtz et al, ASCO 2002 (Abs 141)
BCIRG 001

21. Due to increased toxicity of tac

29. PACS 01 trial
• compared 6 cycles of fluorouracil, epirubicin,
and cyclophosphamide (FEC) with
• sequential regimen of 3 cycles of FEC followed
by 3 cycles of docetaxel (FEC-D) as adjuvant
treatment

32. median follow-up of 60 months,
• 5-year DFS rates were 73.2% with FEC and
78.4% with FEC-D
• Five-year OS rates were 86.7% with FEC and
90.7% with FEC-D,
== 27% reduction in the relative risk of death

34. The US Oncology 9735 trial

35. DOSE DENSITY
• another strategy to maximize benefit from adjuvant
chemotherapy
• smaller tumors grow faster and tumor re growth
between treatment cycles is more rapid when cell kill
is greatest
• dose density reduces the time available for tumor re
growth

36. CALGB 9741 trial
• Dose dense chemotherapy tested
• N= 2005 female patients
• Node positive, II-IIIA
• sequential Adriamycin for 4 doses followed by
paclitaxel - 4 doses followed by cyclophosphamide -4
doses with cycles either every 2 weeks or every 3 weeks
Or
• concurrent AC - 4 doses followed by paclitaxel - 4
doses with cycles every 2 weeks or every 3 weeks

40. relative reduction in risk of recurrence
• 55% for ER negative tumors
• 26% in ER positive tumors

41. • Severe neutropenia less frequent in patients
who received the dose-dense regimens, likely
due to support with filgrastim.
• anemia requiring transfusion was greater in
the dose-dense arms

42. ECOG E1199
• 4,950 stages II–IIIA BC pts
• NODE POSITIVE OR
• HIGH RISK(T2,T3) AXILLARY NODE NEGATIVE
Compared paclitaxel vs docetaxel
3wkly vs wkly
• effect was significant in all pts, including those with ER+/HER2–
tumors.

51. So in adjuant setting

52. NUMBER OF PATIENTS
NUMBR OF TRIAL
N
PATIENTS
TRIALS

53. NEOADJUANT

54. NSABP B 27
• established the role of adding a taxane after
an anthracycline based
• regimen in the neoadjuvant setting.
• N= 2,411 patient

55. B-27 Schema
Operable Breast Cancer
Randomization
I II III
AC x 4
Tam X 5 Yrs
AC x 4
Tam X 5 Yrs
AC x 4
Tam X 5 Yrs
Surgery Docetaxel x 4 Surgery
Surgery Docetaxel x 4
Mamounas, Dec 2001

56. B-27
Pathologic Response (pCR) in Breast
P < 0.001
AC Taxotere
(718 pts)
AC
(1,492 pts)
3.9%
9.8%
No Tumor Non-Invasive
6.9%
18.7%
13.7% 25.6%
20%
10%
0
30%
Mamounas, Dec 2001

57. addition of docetaxel to AC prior to surgery
resulted in a doubling of pCR rate
(26% vs. 13%; )
• no significant improvement in DFS or OS
with either preoperative or postoperative
docetaxel
• PCR- significant predictor of OS
regardless of treatment
(Os improved in those who had pcr)

58. • In a subset analysis, patients who achieved a
clinical partial response after AC had
• improved DFS with preoperative, but not
postoperative, docetaxel
• preferable to administer the entire
chemotherapy regimen prior to surgery if
possible

59. GEPARSEPTO
12 weeks of weekly paclitaxel (80 mg/m2)
weekly nab-paclitaxel(initially 150 mg/m2 but later
reduced to 125 mg/m2 because of toxicities)
• f/ by EC in neoadjuvant setting.
• higher pCR rate in the group receiving nab-pacli (38% vs.
29%)
• higher rate of grade 3 to 4 sensory neuropathy and anemia.
• not yet known whether improvement in pCR will translate
into a survival benefit.

60. Taxane in Metastatic ca breast

61. 8/8/2020 Dr.manu 61

62. 8/8/2020 Dr.manu 62

63. •THANK YOU