This slide was presented in an academic CME in Kolkata in Feb,2020. This presentation focus on recent evidences in the management of Breast cancer.

1. Dr. Abhishek Basu ( Jr )
MD , DNB ( Radiation Oncology )
Clinical Tutor, Medical College Kolkata

2.  Multicenter, open-label, randomized, phase 3 trial designed to evaluate the
efficacy and safety of adjuvant capecitabine monotherapy in
patients with HER2-negative primary breast cancer
who had residual invasive disease after the receipt of standard
neoadjuvant chemotherapy containing anthracycline, taxane, or both .

3. Trial Design
Her 2- neu negative Breast cancer
Age – 20-74 yrs
Stage – I –IIIB, ECOG PS – O-1
NACT – 3 FEC – 3 T
3 FEC – 3TC / 3TC – 3FEC
4 TC only
Surgery
No pathological CR or
Positive Nodes
Capecitabine 1250mg/m2 BD,
D 1-14 , Q3WK × 6-8# +
Standard Tx
Standard Therapy =
HRT +_ RT
5 yr accrual
( 2007-2012) , 5
yr follow up

4. Primary endpoint –
DFS
Time from
randomization to
recurrence
Secondary endpoint
– Overall survival
( Randomization to
death from any
cause )
HR for DFS in
capecitabine arm
assumed to be 0.74

5. Results
74.1 vs
67.6 % 89.2 vs
83.6%
69.8 vs
56.1 %
78.8 vs
70.3%
In hormone receptor +ve – 3 % DFS & 3.4 % OS
benefit only at 5 years.

6. Why Capecitabine ?
Anthracyclines
and taxanes are able to induce
thymidine phosphorylase,
An enzyme that activates
capecitabine .
MC toxicity with cape – HFM
syndrome, grade 3 in 11 %

7. Contemporary Evidence – GEICAM (2003-2010) & FinXX trials failed to show
any significant benefit of adjuvant capecitabine in terms of DFS but patients included
in these trial had a low risk of recurrence, as identified by estrogen receptor– positive
status and low Ki67 status. Also TNBC Accrual was way far less than CREATE- X (
12 % VS 30 %).
Ongoing trial on capecitabine in TNBC - CIBOMA/2004-01
CONCLUSION
Adjuvant capecitabine therapy prolonged DFS and OS among patients
with Her 2 neu negative , breast cancer who had a poor prognosis,
including those with TNBC.

8.  Single Institutional Phase 3 trial – Accrual period : June 2008 – June 2016
 Allowed to follow up till Aug 2017.
 Results Published in January 2019
Inclusion Criteria
1. T3,4 . > 4 LN
2. Stage III or pN + if NACT
3. 18-75 yrs, KPS >60
4. Mastectomy with ALND ,R0
Exclusion Criteria
1. SCV/IMN Mets
2. B/L breast Ca
3. Breast reconstruction
4. Previous RT
5. Distant Mets

9. Trial Design
CFRT : 50
Gy/ 25 # ,
n = 409
HFRT: 43.5
Gy/15 #,
n = 401
Primary Endpoint : Locoregional
Control
Secondary Endpoint : DFS & OS
Statistical consideration
5 yr LRR in CFRT arm was
expected to be 6 % on basis of
previous studies .
With a non inferior margin of 5
% , if the LR in hypo# does not
exceed 11 % then its non inferior .
This correlates with a hazard ratio
[HR] of <1·883).

10. RT techniques
 PMRT to Chest wall , SCV & level III
axillary node.
 CW - 6-9 Mev electron beam , dose
was prescribed at the point on the central
axis with maximum depth dose. A 5 mm
tissue equivalent bolus was applied up to a
median of 40% of the total prescribed dose.
 SCV – 2D ( 3 cm depth )
3DCRT / IMRT – 95 % coverage

12. Results
 Median FU was 58.5 months .
 The 5-year cumulative incidence
of locoregional recurrence was
8·3% (90% CI 5·8–10·7) in the
hypo# RT group compared with
8·1% (90% CI 5·4–10·6) in the
conventional fractionated RT
group .
 Absolute difference 0·2%, 90%
CI –3·0 to 2·6; HR 1·10, 90%
CI 0·72 to 1·69.
p < 0.001
 Hence Non inferiority proved.

13. HFRT arm VS CFRT arm
5 yr DFS 74 % 70 %
5 yr OS 84 % 86 %
Statistically non significant
OS
DFS

14. Toxicity profile
 The hypo # RT group had
less frequent grade 3
acute skin toxicity than
the CFRT group. 3 % vs
8 %
 Other Toxicities were
comparable & none was
fatal. ( Lymphedema ,
shoulder morbidity etc )

15. Contempory evidence & Conclusion
 START A & B
 Limitations - Mastectomy without breast reconstruction .
Exclusion of SCV / IMN mets at presentation .
Only half of the patients received anti Her 2 therapy .
 Conclusion - Hypo # PMRT can be safely advocated in high risk breast
cancer . 10 yr follow up data is awaited.

16. Primary results of NSABP B-39/RTOG 0413 (NRG Oncology) : A
randomized phase III study of conventional whole breast irradiation
(WBI) versus partial breast irradiation (PBI) for women with stage 0,
I, or II breast cancer
( Vicini et al )
 Standard breast-conservation approach consists of lumpectomy plus 5 to 7
weeks of WBI . Accelerated PBI targets and treats the tumor bed area rather
than the entire breast, as is done with WBI.
 PBI also reduces radiation treatment time from the 3 to 6 weeks needed with
WBI to just 5 to 8 days.
 This study ( Multicentre , 387 institutions ) is currently the largest clinical
trial evaluating PBI.

18. For Residents

19. Endpoints & Statistics
 The primary endpoint was IBTR, in both invasive and DCIS subgroups, as
a first recurrence.
 Secondary endpoints included distant disease-free interval (DDFI), RFI—
which was defined as the time from randomization to the development of
first event either local, regional, or distant recurrence, regardless of any
intervening contralateral or second breast cancer and overall survival ,
Patient reported QOL & Toxicity.
 In order to declare accelerated PBI and WBI equivalent in terms of IBTR
risk per a protocol-defined margin, the 90% confidence Interval had to
entirely lie between 0.667 and 1.5.

20. Results
 IBTRs were observed as first events in 161 participants, 90 of which had
received PBI, while 71 had received WBI (HR, 1.22; 90% CI, 0.94-1.58).
 There was an absolute difference of 0.7% (4.6% vs 3.9%) in the 10-year
cumulative incidence of IBTR between accelerated PBI and WBI,
respectively.
 Based on the upper limit of the hazard ratio confidence interval, accelerated
PBI did not meet the criteria for equivalence to WBI in controlling IBTR.
 Additionally, the 10-year RFI rate was higher with WBI at 93.4% compared
with accelerated PBI at 91.8% (HR, 1.33; 95% CI, 1.04-1.69; P = .02); this
1.6% difference was determined to be statistically significant.

21. At 10 yr WBI VS APBI
DDFI 97.1 % 96.7 %
OS 91.3 % 90.6 %
RFI 93.4 % 91.9 %
Grade 3 skin toxicity 7.1 % 9.6 %

22. Conclusion
 Accelerated partial breast irradiation (PBI) following
lumpectomy was marginally not found to be equivalent to
whole breast irradiation (WBI) to control ipsilateral breast
tumor recurrence (IBTR) .
 The trial population was heterogeneous, ranging from Stage 0-
2 breast cancer, and outcome by risk categories are being
analysed.
Thank You