MONARCH 2: FASLODEX 500 mg in combination with abemaciclib 150 mg in patients with disease progression in the neoadjuvant, adjuvant, or early-line metastatic setting1,2*

TRIAL SETUP

MONARCH 2

FASLODEX 500 mg was studied in combination with abemaciclib 150 mg vs FASLODEX plus placebo,* the control arm, in MONARCH 2, a phase 3, randomized, double-blind, placebo-controlled, multicenter, international study in 669 women of any menopausal status with HR-positive, HER2-negative advanced breast cancer (ABC) or mBC that progressed while receiving prior endocrine therapy in the neoadjuvant, adjuvant, or early-line metastatic setting.1,2‡

Patients were randomized 2:1 to FASLODEX plus abemaciclib or the control arm, and stratified according to 2 factors1,2:

MONARCH 2 trial design key inclusion and exclusion criteria
MONARCH 2 trial design key inclusion and exclusion criteria

The primary endpoint was investigator-assessed PFS.2

MONARCH 2 trial design key inclusion and exclusion criteria
MONARCH 2 trial design key inclusion and exclusion criteria

FASLODEX with or without abemaciclib was the first endocrine therapy received by a majority of patients (59.2%) for ABC2

59.2% received as 1st endocrine therapy and 38.3% received as their 2nd endocrine therapy
59.2% received as 1st endocrine therapy and 38.3% received as their 2nd endocrine therapy

CDK4/6i=cyclin-dependent kinase 4/6 inhibitor; ECOG=Eastern Cooperative Oncology Group; 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 and 15 of the first cycle, and on Day 1 of subsequent cycles (every 28 days), and either oral abemaciclib 150 mg or placebo twice daily during each 28-day cycle.1,2

Pre- or perimenopausal women received a gonadotropin-releasing hormone agonist prior to treatment.2

Patients were permitted to have had only 1 prior endocrine therapy for ABC and no prior chemotherapy.2

§Primary endocrine resistance includes patients whose disease relapsed while receiving the first 2 years of neoadjuvant or adjuvant endocrine therapy or progressed while receiving the first 6 months of endocrine therapy for ABC.2

||Secondary endocrine resistance includes patients who were not considered to have primary endocrine therapy resistance.2

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

The ONLY therapy for postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer to receive NCCN Category 1 recommendation as:

  • Combination therapy with palbociclib* and abemaciclib3†
  • Monotherapy3

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

*For postmenopausal women or for premenopausal women receiving ovarian suppression with an LHRH agonist, with hormone receptor-positive and HER2-negative metastatic breast cancer that has progressed after endocrine therapy. 3

Indicated after progression on prior endocrine therapy. 3

NCCNNCCN

 

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Veronica M, age 58*

Patients like Veronica may be appropriate for FASLODEX in combination with abemaciclib1

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

 

*Individual results may vary. 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

8 months ago, Veronica’s original diagnosis was local ER+, HER2-negative breast cancer at age 58  

  • Tumor profile: invasive ductal carcinoma with 62% ER positivity and 40% PgR positivity 
  • Under her doctor’s care, Veronica had a lumpectomy and radiation therapy, and she started adjuvant endocrine therapy 

Failure during adjuvant endocrine therapy 

8 months into adjuvant endocrine therapy, Veronica saw her doctor for chest pain and difficulty breathing 

  • Scans revealed abnormalities in her lungs
  • A subsequent biopsy confirmed the presence of malignant cells
  • Veronica’s disease appears to have potentially progressed quickly, raising concerns about endocrine therapy resistance

Next steps

Now, metastatic progression is confirmed 

  • Veronica’s doctor reviewed her pathology report, which confirmed that the cells were consistent with her primary tumor
  • Tumor profile: 45% ER positivity, 30% PgR positivity, HER2-negative
  • This will be Veronica’s first therapy for metastatic cancer, so her doctor is looking for a potential treatment approach

Because Veronica experienced disease progression within the first 2 years of her adjuvant endocrine therapy, her doctor now considers her to be endocrine therapy-resistant

  • Her doctor is also looking for a potential treatment approach that addresses the ER+ nature of her disease and is proven after endocrine therapy resistance develops 

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. 

Primary endocrine resistance includes patients whose disease relapsed while receiving the first 2 years of neoadjuvant or adjuvant endocrine therapy or progressed while receiving the first 6 months of endocrine therapy for ABC. 1

EFFICACY

FASLODEX in combination with abemaciclib improved median PFS by 76%: 16.4 months vs 9.3 months in the control arm1

Early separation between the curves was observed within 2 months of treatment initiation and continued throughout study assessment.1

  • Investigator-assessed PFS was the primary endpoint of the MONARCH 2 Trial2
  • Objective response rate* in patients with measurable disease more than doubled in the FASLODEX plus abemaciclib arm (n=318): 48.1% (95% CI: 42.6-53.6) and 21.3% (95% CI: 15.1-27.6) in the control arm (n=164)1
    • In the FASLODEX plus abemaciclib arm, complete response was observed in 14 patients (3.1%) and partial response in 143 patients (32.1%). For the control arm, complete and partial responses were observed in 1 patient (0.4%) and 35 patients (15.7%), respectively2

*Objective response rate: Complete response + partial response.

FASLODEX in combination with abemaciclib improved median PFS by 76%
FASLODEX in combination with abemaciclib improved median PFS by 76%

FASLODEX in combination with abemaciclib demonstrated consistent results across patient subgroups2

FASLODEX in combination with abemaciclib demonstrated consistent results across patient subgroups
FASLODEX in combination with abemaciclib demonstrated consistent results across patient subgroups
  • This representation was not designed to assess efficacy in individual subgroups

PgR=progesterone receptor.

In patients with disease progression in the neoadjuvant, adjuvant, or early-line metastatic setting

MONARCH 2 studied 669 women of any
menopausal status11,2*†

Nearly all patients in MONARCH 2 had disease progression on neoadjuvant endocrine therapy, shortly after adjuvant endocrine therapy, or while receiving endocrine therapy for ABC2

Patients developed primary or secondary endocrine therapy resistance during or after previous endocrine therapy.
Patients developed primary or secondary endocrine therapy resistance during or after previous endocrine therapy.
  • 25.2% displayed primary endocrine therapy resistance
  • 73.1% displayed secondary endocrine therapy resistance

All patients had an ECOG performance status of 0 or 12

Eastern Cooperative Oncology Group (ECOG) status for patients
Eastern Cooperative Oncology Group (ECOG) status for patients

The majority of patients were white (56%) and 31.9% were Asian1,2

The majority of patients (72%) had measurable disease2

The median age of patients was 601

Patients with visceral metastases and patients with non-visceral metastases were represented1

In MONARCH 2 Trial patients with visceral metastases and patients with bone-only metastases were represented.
In MONARCH 2 Trial patients with visceral metastases and patients with bone-only metastases were represented.

A majority of patients in both arms had disease progression in the neoadjuvant or adjuvant setting on or after prior aromatase inhibition or chemotherapy2

Prior Aromatase Inhibition and Prior Chemotherapy
Prior Aromatase Inhibition and Prior Chemotherapy

*Pre- or perimenopausal women received a gonadotropin-releasing hormone agonist prior to treatment.2

Criteria included disease progression during neoadjuvant or adjuvant endocrine therapy or ≤12 months after adjuvant endocrine therapy, or while receiving first-line endocrine therapy for metastatic disease.2

In patients with disease progression in the neoadjuvant, adjuvant, or early-line metastatic setting

MONARCH 2 studied 669 women of any menopausal status1,2*†

Nearly all patients in MONARCH 2 had disease progression on neoadjuvant endocrine therapy, shortly after adjuvant endocrine therapy, or while receiving endocrine therapy for ABC2

  • 25.2% displayed primary endocrine therapy resistance
  • 73.1% displayed secondary endocrine therapy resistance

Patients with visceral metastases and patients with non-visceral metastases were represented1

All patients had an ECOG performance status of 0 or 12

Pre or perimenopausal women received a gonadotropin-releasing hormone agonist prior to treatment.2
Criteria included disease progression during neoadjuvant or adjuvant endocrine therapy or ≤12 months after adjuvant endocrine therapy, or while receiving first-line endocrine therapy for metastatic disease.2

A majority of patients in both arms had disease progression in the neoadjuvant or adjuvant setting on or after prior aromatase inhibition or chemotherapy2

The majority of patients were white (56%) and 31.9% were Asian1,2

The majority of patients (72%) had measurable disease2

The median age of patients was 601

SAFETY

Safety profile in MONARCH 21

Adverse reactions ≥10% in FASLODEX + abemaciclib and ≥2% higher than FASLODEX + placebo (control arm)

FASLODEX in combination with abemaciclib adverse reactions
FASLODEX in combination with abemaciclib adverse reactions
  • The most frequent adverse reactions of any grade in the safety population (FASLODEX plus abemaciclib [n=441]; control arm [n=223]) were diarrhea, neutropenia, nausea, fatigue, and abdominal pain. These predominantly occurred at Grade 1 or 22
  • Grade 1 or 2 diarrhea occurred in 322 patients (73.0%) in the FASLODEX plus abemaciclib arm vs 54 patients (24.2%) in the control arm. Grade 3 diarrhea occurred in 59 patients (13.4%) in the FASLODEX plus abemaciclib arm vs 1 patient (0.4%) in the control arm2
  • Serious adverse reactions were reported in 22.4% of patients in the FASLODEX plus abemaciclib arm and 10.8% of patients in the control arm2
  • Venous thromboembolic events (deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, subclavian vein thrombosis, and deep vein thrombosis inferior vena cava) were reported in 5% of patients treated with FASLODEX plus abemaciclib as compared to 0.9% of patients in the control arm.1 Of the patients in the former arm, 4 experienced pulmonary embolism, none of which resulted in death2

Laboratory abnormalities ≥10% in FASLODEX + abemaciclib and ≥2% higher than Control Arm

FASLODEX laboratory abnormalities in MONARCH 2
FASLODEX laboratory abnormalities in MONARCH 2

*Includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, abdominal tenderness.1

Includes upper respiratory tract infection, urinary tract infection, lung infection, pharyngitis, conjunctivitis, sinusitis, vaginal infection, sepsis.1

Includes neutropenia, neutrophil count decreased.1

§Includes anemia, hematocrit decreased, hemoglobin decreased, red blood cell count decreased.1

||Includes leukopenia, white blood cell count decreased.1

Includes platelet count decreased, thrombocytopenia.1

#Includes asthenia, fatigue.1

  • The most frequent adverse reactions of any grade in the safety population (FASLODEX plus abemaciclib [n=441]; control arm [n=223]) were diarrhea, neutropenia, nausea, fatigue, and abdominal pain. These predominantly occurred at Grade 1 or 22
  • Grade 1 or 2 diarrhea occurred in 322 patients (73.0%) in the FASLODEX plus abemaciclib arm vs 54 patients (24.2%) in the control arm. Grade 3 diarrhea occurred in 59 patients (13.4%) in the FASLODEX plus abemaciclib arm vs 1 patient (0.4%) in the control arm2
  • Serious adverse reactions were reported in 22.4% of patients in the FASLODEX plus abemaciclib arm and 10.8% of patients in the control arm2
  • Venous thromboembolic events (deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, subclavian vein thrombosis, and deep vein thrombosis inferior vena cava) were reported in 5% of patients treated with FASLODEX plus abemaciclib as compared to 0.9% of patients in the control arm.1 Of the patients in the former arm, 4 experienced pulmonary embolism, none of which resulted in death2

References: 1. FASLODEX® (fulvestrant) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018. 2. Sledge GW Jr, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35(25):2875-2884. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed April 23, 2018. 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.