1. Fulvestrant ± Palbociclib in ER+/HER2- Breast Cancer: An Extended Follow-up of PALOMA-3
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. PALOMA-3: 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
PALOMA-3: randomized, double-blind, placebo-controlled phase III trial of fulvestrant + palbociclib vs fulvestrant + placebo in ER+/HER2- metastatic breast cancer after progression on endocrine therapy
Fulvestrant + palbociclib associated with significantly longer PFS than control arm; trial ended at interim analysis by DSMB[1]
Current report: longer-term safety, efficacy, and subgroup analyses from PALOMA-3[2]
DSMB, data and safety monitoring board; ER, estrogen receptor; PgR, progesterone receptor.
1. Turner NC, et al. N Engl J Med. 2015;373: Cristofanilli M, et al. SABCS Abstract P
Slide credit: clinicaloptions.com

3. PALOMA-3: Phase III Study Design
Stratified by visceral metastases (yes/no), sensitivity to previous endocrine therapy, menopausal status
Palbociclib 125 mg QD
3 wks on/1 wk off +
Fulvestrant 500 mg IM Q4W
(n = 347)
Pts with HR+/HER2- MBC; PD after endocrine therapy;
≤ 1 chemotherapy regimen for advanced BC
(N = 521)
Tx to PD, toxicity, or study withdrawal
Placebo 3 wks on/1 wk off +
Fulvestrant 500 mg IM Q4W
(n = 174)
BC, breast cancer; CBR, clinical benefit rate; CR, complete response; HR, hormone receptor; MBC, metastatic breast cancer; PD, disease progression SD, stable disease; Tx, treatment.
Primary endpoint: investigator-assessed PFS
Secondary endpoints: ORR, CBR (CR, PR, or SD for ≥ 24 wks), OS, pt-reported outcomes, safety
Slide credit: clinicaloptions.com
Cristofanilli M, et al. SABCS Abstract P

4. PALOMA-3: Baseline Characteristics
Baseline characteristics well balanced between arms; ~ 75% < 65 yrs of age
Characteristic
Palbociclib + Fulvestrant
(n = 347)
Placebo + Fulvestrant
(n = 174)
Median age, yrs (range)
57 (30-88)
56 (29-80)
ER+ and PgR+, %
68.6
63.8
ER+ and PgR-, %
26.2
27.6
Sensitive to prior hormonal Tx, %
79.0
78.2
Metastatic disease at study entry, %
85.3
83.9
Prior AI ± GnRH agonist, %
67.8
Prior tamoxifen ± GnRH agonist, %
18.2
17.2
Prior neo/adjuvant chemotherapy, %
41.5
43.1
Prior lines of tx for metastatic disease, % 1
38.0
40.2 2
25.9
24.7
≥ 3
11.8
9.2
AI, aromatase inhibitor; ER, estrogen receptor; GnRH, gonadotropin-releasing hormone; PgR, progesterone receptor; tx, treatment.
Cristofanilli M, et al. SABCS Abstract P Turner NC, et al. N Engl J Med. 2015;373:
Slide credit: clinicaloptions.com

5. PALOMA-3: PFS in Overall Population and Specific Pt Subgroups
Median follow-up: 8.9 mos
Median PFS, Mos (95% CI)
Palbociclib + Fulvestrant
(n = 345)
Placebo +
Fulvestrant
(n = 172) HR
(95% CI)
P Value
ITT population
9.5 ( )
4.6 ( )
0.45 ( )
< .0001
Pre-/perimenopausal pts
9.5 (7.4-NE)
5.6 ( )
0.50 ( )
.0065
Postmenopausal women
9.9 ( )
3.9 ( )
0.45 ( )
No earlier systemic therapy for metastatic disease
5.4 ( )
0.55 ( )
.0214
Disease responsive to earlier endocrine therapy
10.2 ( )
4.2 ( )
0.42 ( )
AIs as most recent therapy
3.7 ( )
0.42 ( )
AI, aromatase inhibitor; ITT, intent to treat; NE, not evaluable.
Slide credit: clinicaloptions.com
Cristofanilli M, et al. SABCS Abstract P

6. PALOMA-3: Response and Clinical Benefit Rates
Median follow-up: 8.9 mos
Outcome, % (95% CI)
Palbociclib + Fulvestrant
(n = 345)
Placebo +
Fulvestrant
(n = 172)
Odds Ratio
(95% CI)
P Value
ITT population
ORR
CBR
19.0 ( )
66.6 ( )
8.6 ( )
39.7 ( )
2.47 ( )
3.05 ( )
.0019
< .0001
Pts with measurable disease at BL
24.6 ( ) NR
10.9 ( )
2.69 ( )
3.10 ( )
.0012
BL, baseline; CBR, clinical benefit rate; ITT, intent to treat; NR, not reported.
Slide credit: clinicaloptions.com
Cristofanilli M, et al. SABCS Abstract P

7. Palbociclib + Fulvestrant Palbociclib + Fulvestrant
PALOMA-3: Grade 3/4 AEs
Nonhematologic AE, n
Palbociclib + Fulvestrant
(n = 345)
Placebo +
Fulvestrant
(n = 172)
Infections 6 1
Fatigue 8
Headache 2
Vomiting
Decreased appetite 3
Rash
Back pain 4
Arthralgia
Stomatitis
Dizziness
Dyspnea
Pyrexia
Insomnia
Hematologic Event, n (%)
Palbociclib + Fulvestrant
(n = 345)
Placebo +
Fulvestrant
(n = 172)
Neutropenia
223 (65)
1 (< 1)
Anemia
10 (3)
3 (2)
Leukopenia
93 (27)
2 (1)
Thrombocytopenia
6 (2)
Febrile neutropenia incidence was similar with palbociclib + fulvestrant and placebo + fulvestrant (0.9% vs 0.6%, respectively)
Discontinuations due to AEs were similar with palbociclib + fulvestrant and placebo + fulvestrant (4% vs 2%, respectively)
AE, adverse event.
Slide credit: clinicaloptions.com
Cristofanilli M, et al. SABCS Abstract P

8. PALOMA-3: Conclusions
In pts with ER+/HER2- breast cancer that has progressed after endocrine therapy
The significant improvement in efficacy with the addition of palbociclib to fulvestrant was maintained through longer follow-up
Benefit demonstrated across all subgroups
No new safety concerns were identified; certain hematologic AEs were more common with palbociclib than fulvestrant alone
The incidence of febrile neutropenia was similar for both treatment arms
AE, adverse event; ER, estrogen receptor.
Slide credit: clinicaloptions.com
Cristofanilli M, et al. SABCS Abstract P

9. Go Online for More CCO Coverage of SABCS 2015!
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