1. Neoadjuvant Palbociclib + Anastrozole in ER+/HER2- 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.
ER, estrogen receptor.
This program is supported by educational grants from Genentech and Novartis.

2. Neoadjuvant Palbociclib + Anastrozole: Background
Standard of care therapy for pts with ER+ and/or PgR+ breast cancer includes selective ER modulators and aromatase inhibitors
Overexpression of CDK 4/6 associated with proliferation of ER+ and/or PgR+ breast cancer
Palbociclib, first-in-class oral selective CDK 4/6 inhibitor
Active in metastatic breast cancer in combination with aromatase inhibitor or fulvestrant[1-3]
Current study evaluates the combination of palbociclib + anastrozole as neoadjuvant therapy in pts with stage II/III ER+/HER2- breast cancer[4]
ER, estrogen receptor; PgR, progesterone receptor.
1. Cristofanilli M, et al. SABCS Abstract P Turner NC, et al. N Engl J Med. 2015;373: Finn RS, et al. Lancet Oncol. 2015;16: Ma CX, et al. SABCS Abstract S6-05.
Slide credit: clinicaloptions.com

3. Neoadjuvant Palbociclib + Anastrozole in ER+/HER2- BC: Trial Design
Pts with ER+/HER2-, stage II or III BC,
ECOG PS 0-2
(N = 50)
Anastrozole 1 mg QD x 28 days x 6 cycles*
Palbociclib 125 mg QD Days 1-21 of 28
Concurrent with anastrozole cycles 1-4
Surgery
*Cycle 0 with no palbociclib, cycles 1-4 with palbociclib, cycle 5 with palbociclib added for days prior to surgery only in the last 20 pts enrolled; to assess molecular changes with anastrozole ± palbociclib
Primary endpoint: complete cell cycle arrest, defined as Ki67 ≤ 2.7% on Day 15 after first 2 wks of the combination treatment.
Protocol calls for removal from study if Ki67 > 10% at biopsy
Secondary endpoints: clinical, radiologic, pathologic response, toxicity, rate of complete cell cycle arrest and rate of change in Ki67 by subtype and PIK3CA mutations; explore effect of palbociclib on molecular resistance mutations using next-generation sequencing on prespecified gene panel
BC, breast cancer; ECOG PS, Eastern Cooperative Oncology Group performance status; ER, estrogen receptor.
Slide credit: clinicaloptions.com
Ma CX, et al. SABCS Abstract S6-05.

4. Palbociclib + Anastrozole
Neoadjuvant Palbociclib + Anastrozole in ER+/HER2- BC: Baseline Characteristics
Characteristic
Palbociclib + Anastrozole
(N = 50)
Median age, yrs (range)
57 (34-79)
Premenopausal, % 36
Postmenopausal, % 64
Clinical stage, %
II/IIA
IIB
IIIA
IIIB/C 40 32 24 4
BC, breast cancer; ER, estrogen receptor.
Slide credit: clinicaloptions.com
Ma CX, et al. SABCS Abstract S6-05.

5. Palbociclib + Anastrozole
Neoadjuvant Palbociclib + Anastrozole in ER+/HER2- BC: Complete Cell Cycle Arrest
Primary endpoint of CCCA, defined as Ki67 ≤ 2.7% on Day 15 after first 2 wks of the combination treatment
Study objective: demonstrate a CCCA rate of 66%
Response, % (90% CI)
Palbociclib + Anastrozole
(n = 45)
Overall group (n = 45)
87 (75-94)
PIK3CA wild-type genotype (n = 28)
79 (62-90)
PIK3CA mutant genotype (n = 15)
100 (82-100)
PIK3CA genotype undetermined (n = 2)
100 (NE)
BC, breast cancer; CCCA, complete cell cycle arrest; ER, estrogen receptor; NE, not estimable.
Slide credit: clinicaloptions.com
Ma CX, et al. SABCS Abstract S6-05.

6. Palbociclib + Anastrozole
Neoadjuvant Palbociclib + Anastrozole in ER+/HER2- BC: CCCA by Tx Component
Response, n
Palbociclib + Anastrozole
(N = 43)
Ki67 < 2.7% with anastrozole alone 11
Ki67 < 2.7% with addition of palbociclib 26
Ki67 > 2.7% throughout treatment 6
BC, breast cancer; CCCA, complete cell cycle arrest; ER, estrogen receptor; Tx, treatment.
Slide credit: clinicaloptions.com
Ma CX, et al. SABCS Abstract S6-05.

7. Neoadjuvant Palbociclib + Anastrozole in ER+/HER2- BC: CCCA Subgroup Analyses
ΔKi67 Geometric Mean, P Value
Cycle 0 Day 1 vs
Cycle 1 Day 1
Cycle 1 Day 1 vs
Cycle 1 Day 15
Ki67 < 2.7% by PIK3CA genotype
Wild type, n = 28
Mutant, n = 15
< .001↓*
.002↓
< .001↓
Ki67 < 2.7% by intrinsic subtype
Luminal A, n = 18
Luminal B, n = 11
ΔKi67 Geometric Mean, P Value
Cycle 1 Day 1 vs
Surgery
Cycle 1 Day 15 vs
Palbociclib administration before surgery
4 wks washout, n = 26
Additional palbociclib days before surgery, n = 8
.0187↑
.0111↓
< .0001↑
.2885↑
BC, breast cancer; CCCA, complete cell cycle arrest; ER, estrogen receptor.
*Arrows indicate direction of change.
Slide credit: clinicaloptions.com
Ma CX, et al. SABCS Abstract S6-05.

8. Palbociclib + Anastrozole
Neoadjuvant Palbociclib + Anastrozole in ER+/HER2- BC: Clinical Response
Response assessed for all pts who completed at least 3 cycles (n = 41)
5 pts off study per protocol: > 10% Ki67, n = 4; goserelin failure, n = 1
Response, n (%)
Palbociclib + Anastrozole
(N = 46)
Overall response
31 (67; 95% CI: 54-79) CR
11 (24) PR
20 (43)
Stable disease
6 (13)
BC, breast cancer; ER, estrogen receptor.
Slide credit: clinicaloptions.com
Ma CX, et al. SABCS Abstract S6-05.

9. Palbociclib + Anastrozole Palbociclib + Anastrozole
Palbociclib + Anastrozole in ER+/HER2- BC: Grade 3/4 AEs and Dose Reductions
AE, %
Palbociclib + Anastrozole
(N = 50)
Neutropenia 26
ALT elevation 4*
AST elevation 2*
Hypertension
Cholecystitis
*All grade 3.
No deaths or febrile neutropenia reported
1-Level Dose Reduction by Related AE, n
Palbociclib + Anastrozole
(N = 50)
Grade 3 increase in ALT or AST 2
Grade 3 neutropenia 3
Grade 4 neutropenia 1
Grade 2 rash
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BC, breast cancer; ER, estrogen receptor.
Slide credit: clinicaloptions.com
Ma CX, et al. SABCS Abstract S6-05.

10. Neoadjuvant Palbociclib + Anastrozole in ER+/HER2- BC: Conclusions
In pts with ER+/HER2- BC treated with palbociclib and anastrozole in the neoadjuvant setting:
The combination improved cell cycle arrest over that seen with anastrozole alone
Benefit seen regardless of PIK3CA genotype or luminal A or B status
The combination was well tolerated with a low rate of grade 3/4 AEs, no deaths, and no febrile neutropenia
Rebound Ki67 level after washout indicates that palbociclib efficacy requires ongoing administration
The authors conclude that this study supports further evaluation of this combination in the adjuvant setting
AE, adverse event; BC, breast cancer; ER, estrogen receptor.
Slide credit: clinicaloptions.com
Ma CX, et al. SABCS Abstract S6-05.

11. Go Online for More CCO Coverage of SABCS 2015!
Short slideset summaries of all the key data Additional CME-certified slideset with expert faculty commentary on all the key studies
clinicaloptions.com/oncology