PALOMA-3: the first phase 3 trial to study FASLODEX (500 mg) in combination with palbociclib (125 mg)1,2

TRIAL SETUP

PALOMA-3

FASLODEX 500 mg was studied in combination with palbociclib 125 mg vs FASLODEX plus placebo,* the control arm, in PALOMA-3, a phase 3, international, randomized, double-blind, parallel-group, multicenter study in women (N=521) with HR-positive, HER2-negative ABC or mBC, regardless of their menopausal status, whose disease progressed on or after prior endocrine therapy.1,2

Patients were randomized 2:1 to FASLODEX plus palbociclib or the control arm, and stratified by documented sensitivity to prior hormonal therapy, menopausal status at study entry (pre/peri vs postmenopausal), and presence of visceral metastases.1

The primary endpoint was investigator-assessed PFS, evaluated according to RECIST v.1.1. A prespecified secondary endpoint was investigator-assessed overall survival.1

Prior therapy in PALOMA-3

  • All patients received prior systemic therapy1
  • 75% of patients received a previous chemotherapy regimen, 34% of which was in the metastatic setting.1,2 Patients were permitted to have 1 prior line of chemotherapy for advanced disease and/or multiple lines of prior endocrine therapy2

ABC=advanced breast cancer; HER2=human epidermal growth factor receptor 2; HR=hormone receptor; mBC=metastatic breast cancer; PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumors.

*Patients in both arms received FASLODEX 500 mg by intramuscular injection on Days 1, 15, and 29 of the first month, and every 28 (±3) days thereafter, and either oral palbociclib 125 mg or placebo for 21 consecutive days followed by 7 days off treatment.1

Women who were either premenopausal (meaning that they had not reached menopause) or perimenopausal (meaning that their bodies were approaching menopause) were therapeutically induced to become postmenopausal and represented 20.7% of the study population.1-4

Indication for FASLODEX

Combination Therapy
  • FASLODEX in combination with palbociclib or abemaciclib is indicated for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in women with disease progression after endocrine therapy

X

NCCN

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer recommend the use of fulvestrant (FASLODEX) as a Category 1 option*:

  • As first-line in combination with a CDK4/6 inhibitor6*
  • In combination with a CDK4/6 inhibitor after progression on endocrine therapy (ET)6
  • As monotherapy6

NCCN=National Comprehensive Cancer Network ® (NCCN ®).

 

*CDK4/6i in combination with fulvestrant may be considered as a treatment option for first-line therapy for women who are postmenopausal with hormone-receptor–positive, HER2-negative metastatic breast cancer. 6

 

FASLODEX is only indicated in combination with ribociclib as first-line therapy for patients without progression on prior endocrine therapy. FASLODEX in combination with ribociclib, palbociclib or abemaciclib is indicated for patients with disease progression after ET.

NCCNNCCN

 

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Phyllis M, age 60*

Patients like Phyllis may be appropriate for FASLODEX in combination with either abemaciclib or palbociclib1

  • Initial diagnosis: pT2N1M0
  • Site of metastasis: hip bone
  • Stage: IV
  • ECOG performance status: 1

 

*Individual results may vary. This is not a real patient. This representation was not designed to reflect efficacy for an individual patient subgroup.

When your patient is a woman with HR-positive, HER2-negative ABC or mBC with disease progression after endocrine therapy…

Events from initial diagnosis to metastatic progression

Original diagnosis

6 years ago, Phyllis’ original diagnosis was local ER+, HER2-negative breast cancer at age 54

  • Tumor profile: invasive ductal carcinoma with 75% ER positivity and 50% PgR positivity
  • Under her doctor’s care, Phyllis had a lumpectomy and radiation therapy, and she started adjuvant AI therapy
  • After 5 years with no signs of progression, her doctor chose to discontinue therapy

Failure after adjuvant AI

Approximately 10 months after discontinuing therapy, Phyllis saw her doctor for flank pain

  • Scans revealed abnormalities in her left hip bone
  • A subsequent biopsy confirmed the presence of malignant cells
  • If disease progression is confirmed, Phyllis’ doctor may consider trying a therapy with a different mechanism of action

Next steps

Now, metastatic progression is confirmed 

  • Phyllis’ doctor reviewed her pathology report, which confirmed that the cells were consistent with her primary tumor
  • Tumor profile: 60% ER positivity, 42% PgR positivity, HER2-negative
  • This will be Phyllis’ first therapy for metastatic cancer, so her doctor is looking for a potential treatment approach

Because Phyllis has ER+ disease, her doctor is interested in a potential treatment approach that addresses the estrogen receptor-dependent nature of her disease

ABC=advanced metastatic breast cancer; ECOG=Eastern Cooperative Oncology Group; ER+=estrogen receptor-positive; HER2=human epidermal growth factor receptor 2; HR=hormone receptor; mBC=metastatic breast cancer; PgR=progesterone receptor.

EFFICACY

FASLODEX in combination with palbociclib significantly increased PFS vs the control arm: median 9.5 months vs 4.6 months, respectively1

FASLODEX in combination with palbociclib significantly increased PFS vs control
FASLODEX in combination with palbociclib significantly increased PFS vs control

Objective response rate* for patients with measurable disease: 24.6% (95% CI: 19.6-30.2) for the FASLODEX plus palbociclib arm (n=267) and 10.9% (95% CI: 6.2-17.3) for the control arm (n=138)1

CI=confidence interval; HR=hazard ratio.

*Based on confirmed responses.

OS results: 34.9 months vs 28.0 months for FASLODEX + palbociclib vs control arm, respectively6

FASLODEX in combination with palbociclib OS results
FASLODEX in combination with palbociclib OS results
  • After a median follow-up duration of 44.8 months and 60% data maturity, there was no statistical difference in OS between the 2 treatment groups6
    • 57.9% (201/347) of patients in the FASLODEX + palbociclib group had died6
    • 62.6% (109/174) of patients in the FASLODEX + placebo group had died6

OS=overall survival.

*Stratification according to presence or absence of sensitivity to previous endocrine therapy and the presence or absence of visceral metastases at randomization in the intention-to-treat population.6

FASLODEX in combination with palbociclib showed consistent results across select subgroups1,2

FASLODEX in combination with palbociclib showed consistent results across select subgroups
FASLODEX in combination with palbociclib showed consistent results across select subgroups
  • Study was not powered to show statistical significance between or within individual subgroups

National Comprehensive Cancer Network® (NCCN®) recommends fulvestrant (FASLODEX) in combination with palbociclib

The NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) recommend the use of fulvestrant (FASLODEX) in combination with palbociclib as a Category 1 option for women with HR-positive, HER2-negative mBC that progressed on endocrine therapy.6

In patients with disease progression on or after prior endocrine therapy

PALOMA-3 phase 3 trial studied 521 women of any menopausal status1*

Patients received FASLODEX 500 mg + palbociclib 125 mg or FASLODEX + placebo, the control arm1

Number of prior treatments for metastatic disease
Number of prior treatments for metastatic disease
  • Approximately 25% of patients in the FASLODEX plus palbociclib arm (n=347) received this regimen as their first therapy for metastatic disease5
  • Approximately 75% of patients in the FASLODEX plus palbociclib arm received this regimen as their second or later therapy for metastatic disease5

A majority (66.6%) had more than 1 metastatic site, with levels of disease from non-visceral to visceral involvement1,2

PALOMA-3 Trial Metastatic Breast Cancer Disease Sites
PALOMA-3 Trial Metastatic Breast Cancer Disease Sites
PALOMA-3 Trial Metastatic Breast Cancer Disease Sites
PALOMA-3 Trial Metastatic Breast Cancer Disease Sites

Eastern Cooperative Oncology Group (ECOG) performance status requirement: 0 or 11,2

Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status

A majority were under 65 years of age1,5

PALOMA-3 Trial Median Age Range
PALOMA-3 Trial Median Age Range
  • Median age 57 years (range 29-88)

*A phase 3 international, randomized, double-blind, parallel-group, multicenter study. Patients in both arms received FASLODEX 500 mg by intramuscular injection on Days 1, 15, and 29 of the first month, and every 28 (±3) days thereafter, and either oral palbociclib 125 mg or placebo for 21 consecutive days followed by 7 days off treatment.1,2

Women who were either premenopausal (meaning that they had not reached menopause) or perimenopausal (meaning that their bodies were approaching menopause) were therapeutically induced to become postmenopausal and represented 20.7% of the study population.1-4

Per protocol, visceral refers to lung, liver, brain, pleural, and peritoneal involvement, and was a study stratification factor.2

SAFETY

Safety profile in PALOMA-31

Adverse Reactions (≥10%) in PALOMA-3

FASLODEX + palbociclib adverse reactions
FASLODEX + palbociclib adverse reactions

Grading according to Common Terminology Criteria for Adverse Events 4.0.

N/A=not applicable.

*Infections include all reported preferred terms (PTs) that are part of the System Organ Class Infections and infestations.1

Most common infections (≥1%) include: nasopharyngitis, upper respiratory infection, urinary tract infection, influenza, bronchitis, rhinitis, conjunctivitis, pneumonia, sinusitis, cystitis, oral herpes, respiratory tract infection, gastroenteritis, tooth infection, pharyngitis, eye infection, herpes simplex, and paronychia.1

Stomatitis includes: aphthous stomatitis, cheilitis, glossitis, glossodynia, mouth ulceration, mucosal inflammation, oral pain, oropharyngeal discomfort, oropharyngeal pain, stomatitis.1

§Grade 1 events - 17%; Grade 2 events - 1%.1

||Grade 1 events - 6%.1

Rash includes: rash, rash maculopapular, rash pruritic, rash erythematous, rash papular, dermatitis, dermatitis acneiform, toxic skin eruption.1

  • Permanent discontinuation associated with an adverse reaction occurred in 19 of 345 (6%) patients receiving FASLODEX plus palbociclib and in 6 of 172 (3%) patients within the control arm1
  • Adverse reactions leading to discontinuation for those patients receiving FASLODEX plus palbociclib included fatigue (0.6%), infections (0.6%), and thrombocytopenia (0.6%)1

References: 1. FASLODEX® (fulvestrant) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019. 2. Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17(4):425-439. 3. NCI Dictionary of Cancer Terms: premenopausal. National Cancer Institute website. https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45268. Accessed July 6, 2017. 4. NCI Dictionary of Cancer Terms: perimenopausal. National Cancer Institute website. https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45826. Accessed July 7, 2017. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed February 26, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 6. Turner NC, Ro J, André F, et al. Palbociclib in hormone-receptor positive advanced breast cancer. N Engl J Med. 2015;373(3):209-219.

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MONARCH 2