1. CREATE-X: Adjuvant Capecitabine in HER2-Negative Breast Cancer
CCO Independent Conference Coverage*: The 2015 Annual Meeting of the CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2015
San Antonio, Texas
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from Genentech and Novartis.

2. CREATE-X: Background
Pts with pathologic residual disease after standard anthracycline/taxane neoadjuvant chemotherapy have a high risk of relapse
Adjuvant chemotherapy in pts who received neoadjuvant chemotherapy may not prolong survival
The phase III CREATE-X trial evaluated efficacy of adjuvant capecitabine for HER2-negative breast cancer pts with residual invasive disease (non-pCR, node positive) following anthracycline/taxane neoadjuvant chemotherapy
pCR, pathologic complete response.
Slide credit: clinicaloptions.com
Toi M, et al. SABCS Abstract S1-07.

3. CREATE-X: Study Design
Preplanned interim analysis of a randomized, open-label phase III study[1]
Stratified by ER status, age, neoadjuvant chemotherapy, use of 5-FU, institution, node status
Wk 24
Capecitabine
2500 mg/m²/day PO Days 1-14
Q3W for 8 cycles‡
Hormonal therapy if ER/PgR+
(n = 455)†
Pts yrs of age
with stage I-IIIB HER2- BC and residual disease
(non-pCR, N+) after neoadjuvant chemotherapy* and surgery;
ECOG PS 0 or 1;
no previous oral fluoropyrimidines
(N = 910)†
Hormonal therapy if ER/PgR+
No further therapy if ER/PgR-
(n = 455)†
Primary endpoint: DFS
Secondary endpoints: OS, time from first day of preoperative chemotherapy to recurrence or death, safety, cost-effectiveness
5-FU, 5-fluorouracil; BC, breast cancer; ECOG, Eastern Cooperative Oncology Group; ER, estrogen receptor; IDMC, Independent Data Monitoring Committee; N+, positive lymph nodes; pCR, pathologic complete response; PgR, progesterone receptor; PS, performance status.
*Anthracycline/taxane, anthracycline containing, or docetaxel/cyclophosphamide.
†25 pts were removed from treatment (n = 10) and control (n = 15) arms due to failure to meet eligibility criteria.
‡IDMC recommended extension to 8 cycles following interim safety analysis
of first 50 pts receiving 6 cycles.[2]
1. Toi M, et al. SABCS Abstract S1-07.
2. Ohtani S, et al. SABCS Abstract P
Slide credit: clinicaloptions.com

4. CREATE-X: Baseline Characteristics
Capecitabine
(n = 440)
No Capecitabine
(n = 445)
Age, median yrs (range)
48 (25-74)
Menopausal status, %
Pre
Post
59.3
40.7
56.0
44.0
Stage, %
I, IIA, IB
IIIA, IIIB
58.9
40.5
62.0
37.5
Hormonal receptor status, %
ER+ or PgR+
ER- and PgR-
63.9
33.4
62.9
33.5
Lymph nodes with metastatic disease, %
1-3
≥ 4
39.3
22.7
38.7
39.1
22.2
Histologic effect grading by NAC, %
0, 1a, 1b
2, 3
56.4
41.6
52.6
45.4
ER, estrogen receptor; NAC, neoadjuvant chemotherapy; PgR, progesterone receptor.
Slide credit: clinicaloptions.com
Toi M, et al. SABCS Abstract S1-07.

5. CREATE-X: Pt Treatment Status and Disposition
Characteristic
Capecitabine
(n = 440)
No Capecitabine
(n = 445)
Neoadjuvant chemotherapy, %
Anthracycline containing
Sequential anthracycline/taxane
Concurrent anthracycline/taxane
Docetaxel + cyclophosphamide
5-FU containing
4.1
81.1
13.6
1.1
59.1
3.6
83.4
11.9
0.7
60.4
Adjuvant endocrine therapy, %
Premenopausal
Postmenopausal
42.5
24.5
40.0
28.5
Previous RT, %
72.3
73.5
Measure, % (n = 439*)
6-Cycle Regimen
(n = 159)
8-Cycle Regimen
(n = 280)
Completed all cycles
58.0
37.9
Dose reduction
23.9
37.1
Discontinuation
18.2
25.0
Relative dose intensity, mean ( SD)
87.9 ( 21.6)
79.1 ( 29.0)
5-FU, 5-fluorouracil; RT, radiation therapy; SD, standard deviation.
*Pts who received capecitabine; data for 1 pt not reported.
Slide credit: clinicaloptions.com
Toi M, et al. SABCS Abstract S1-07.

6. CREATE-X: 5-Yr Efficacy
Capecitabine achieved significantly higher 5-yr DFS and OS in HER2- BC pts with residual disease
Characteristic, %
Capecitabine
(n = 440)
No Capecitabine
(n = 445)
HR (95% CI)
P Value
5-yr DFS
74.1
67.7
0.70
( )
.00524
5-yr OS
89.2
83.9
0.60
( )
< .01
BC, breast cancer; DFS, disease-free survival; OS, overall survival.
Slide credit: clinicaloptions.com
Toi M, et al. SABCS Abstract S1-07.

7. CREATE-X: DFS by SubgroupHR
(95% CI)
Total (N = 885)
0.70 ( )
Age
< 50 yrs (n = 531)
≥ 50 yrs (n = 354)
0.72 ( )
0.68 ( )
Hormone receptor status
Positive (n = 561)
Negative (n = 296)
0.84 ( )
0.58 ( )
Node stage
ypN0 (n = 345)
ypN1 (n = 339)
ypN2 or 3 (n = 199)
0.88 ( )
0.54 ( )
0.82 ( )
Path grade by NAC
0-1b (n = 482)
2-3 (n = 385)
0.63 ( )
0.84 ( )
Subgroup HR
(95% CI)
Total (N = 885)
0.70 ( )
Taxane-containing NAC
Yes (n = 849)
No (n = 36)
0.87 ( )
5-FU–containing NAC
Yes (n = 529)
No (n = 356)
0.74 ( )
0.65 ( )
Nationality
Japanese (n = 599)
Korean (n = 286)
0.74 ( )
0.63 ( )
5-FU, 5-fluorouracil; NAC, neoadjuvant chemotherapy; ypN, posttreatment pathologic node stage.
Slide credit: clinicaloptions.com
Toi M, et al. SABCS Abstract S1-07.

8. CREATE-X: Adverse Events
AE, %
Capecitabine
(n = 440)
No Capecitabine
(n = 445)
P Value
Neutropenia, grade ≥ 3
6.6
1.6
< .001
Diarrhea, grade ≥ 3
3.0
0.4
.004
Capecitabine hand–foot syndrome, grade: 1 2 3
27.7
36.4
25.0
10.9 --
All grade AEs that are significantly higher in capecitabine arm include:
Leukopenia, neutropenia, anemia, thrombocytopenia, elevated ALT/AST, total bilirubin, appetite loss, diarrhea, stomatitis, fatigue
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase.
Slide credit: clinicaloptions.com
Toi M, et al. SABCS Abstract S1-07.

9. CREATE-X: Conclusions
Adjuvant capecitabine significantly improved DFS and OS in HER2- breast cancer pts with pathologic residual disease following standard anthracycline/ taxane neoadjuvant chemotherapy
The authors concluded that the risk vs benefit of capecitabine therapy supports further investigation of its use as adjuvant therapy in this breast cancer population
Cost–benefit analysis of adjuvant capecitabine in this population is planned
DFS, disease-free survival; OS, overall survival.
Toi M, et al. SABCS Abstract S1-07.

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