MONALEESA-3: the first Phase 3 trial to study FASLODEX (500 mg) in combination with ribociclib (600 mg)

TRIAL SETUP

MONALEESA-3

FASLODEX 500 mg was studied in combination with ribociclib 600 mg vs FASLODEX plus placebo, the control arm, in MONALEESA-3, a Phase 3, randomized, double-blind study of postmenopausal women (N=726) with HR-positive, HER2-negative advanced breast cancer who were treatment naïve or who had progressed after 1 line of prior ET for advanced disease.1

Patients were randomized 2:1 to FASLODEX plus ribociclib or the control arm. Random assignment was stratified by the presence or absence of lung or liver metastases and prior endocrine therapy.1

The primary endpoint was locally assessed PFS. To evaluate this endpoint, a BIRC performed a central assessment of PFS in a random subgroup of patients.

The major efficacy outcome measure was investigator-assessed PFS using RECIST v.1.1.1

FASLODEX MONALEESA-3 clinical trial design
FASLODEX MONALEESA-3 clinical trial design

CDK4/6i=cyclin-dependent kinase 4/6 inhibitor; ET=endocrine therapy; HER2=human epidermal growth factor receptor 2; HR=hormone receptor; 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, 29, and once monthly thereafter, with either oral ribociclib 600 mg once daily or placebo once daily for 21 consecutive days followed by 7 days off.1

In the metastatic setting.

§Fourteen patients not included because of missing data or criteria not being met.

Indication for FASLODEX

Combination Therapy

FASLODEX is indicated for the treatment of:

  • HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine-based therapy or following disease progression on 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 inhibitor2*
  • In combination with a CDK4/6 inhibitor after progression on endocrine therapy (ET)2
  • As monotherapy2

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. 2

 

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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Lisa, age 65*

Patients like Lisa may be appropriate for FASLODEX in combination with ribociclib1

  • Recurrence >2 years after
    cessation of adjuvant ET
  • Site of metastasis: bone and liver
  • 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 postmenopausal woman with HR-positive, HER2-negative ABC or mBC with disease progression after endocrine therapy…

Events from initial diagnosis to late recurrence

Original diagnosis

8 years ago, Lisa’s original diagnosis was early ER+, HER2-negative breast cancer at age 58.

  • Tumor profile: invasive ductal carcinoma with 80% ER positivity 
  • Under her doctor’s care, Lisa 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

Recurrence after adjuvant AI

After 2 years of completing adjuvant AI therapy, Lisa saw her doctor for lower-back pain.

  • Scans revealed abnormalities in a lower vertebra and a single lesion in her liver
  • Subsequent biopsy confirmed cells were consistent with primary tumor

Next steps

Now, Lisa has been diagnosed with mBC.

  • Tumor profile: 70% ER positivity, HER2-negative
  • Lisa and her doctor plan to discuss her initial endocrine therapy for mBC

Because Lisa has ER+ disease that has recurred following adjuvant endocrine therapy on an AI, her doctor is interested in a potential treatment approach that addresses the estrogen-receptor–dependent nature of her disease.

ABC=advanced breast cancer; AI=aromatase inhibitor; ECOG=Eastern Cooperative Oncology Group; ER=estrogen receptor; ET=endocrine therapy; mBC=metastatic breast cancer.

EFFICACY

FASLODEX in combination with ribociclib significantly increased PFS vs the control arm: median 20.5 months vs 12.8 months, respectively1

Overall response rate* in patients with measurable disease at baseline:
40.9% (95% CI: 35.9-45.8) for the FASLODEX plus ribociclib arm (n=379) and 28.7% (95% CI: 22.1- 35.3) for the control arm (n=181)1

At the time of the PFS analysis, 17% of patients had died and overall survival data were immature.1

CI=confidence interval; HR=hazard ratio.

*Based on confirmed responses.

FASLODEX in combination with ribociclib improved median PFS vs control
FASLODEX in combination with ribociclib improved median PFS vs control
Overall response rate* in patients with measurable disease at baseline:
40.9% (95% CI: 35.9-45.8) for the FASLODEX plus ribociclib arm (n=379) and 28.7% (95% CI: 22.1- 35.3) for the control arm (n=181)1

At the time of the PFS analysis, 17% of patients had died and overall survival data were immature.1

CI=confidence interval; HR=hazard ratio.

FASLODEX in combination with ribociclib showed consistent results across select subgroups1

FASLODEX in combination with ribociclib showed consistent results across patient subgroups
FASLODEX in combination with ribociclib showed consistent results across patient subgroups
  • Study was not powered to show statistical significance between or within individual subgroups
  • Due to both the small sample size and limited number of events, the hazard ratio for the Asian subgroup of patients should be interpreted cautiously1

AI=aromatase inhibitor; CI=confidence interval; ECOG PS=Eastern Cooperative Oncology Group Performance Status; ET=endocrine therapy; HR=hormone receptor.

 

*Prior ET for advanced disease; 14 patients were not included in the prior ET subgroup analysis because of missing data or criteria not being met.

In patients who were treatment naïve or had up to 1 line of prior ET in the advanced setting

MONALEESA-3 phase 3 trial studied 726 postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer1

Patients received FASLODEX 500 mg + ribociclib 600 mg or FASLODEX + placebo, the control arm1

Prior treatment

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.

 

 

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.

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

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

 

 

A majority were under 65 years of age3

 

ABC=advanced breast cancer; ET=endocrine therapy.

  • Median age 63 years (range 31-89)

In patients who were treatment naïve or had up to 1 line of prior ET in the advanced setting

MONALEESA-3 phase 3 trial studied 726 postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer1

ABC=advanced breast cancer; ET=endocrine therapy.


Patients received FASLODEX 500 mg + ribociclib 600 mg or FASLODEX + placebo, the control arm1

Prior treatment

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.

 

 

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.

 

 

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

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

 

 

A majority were under 65 years of age3

  • Median age 63 years (range 31-89)

SAFETY

Safety profile in MONALEESA-3

Adverse Reactions Occurring in ≥10% and ≥2% Higher Than Control Arm in MONALEESA-3 (All Grades)3

FASLODEX + ribociclib adverse reactions
FASLODEX + ribociclib adverse reactions
  • Among patients receiving FASLODEX plus ribociclib, 8% were reported to have permanently discontinued both FASLODEX and ribociclib, and 9% were reported to have discontinued ribociclib alone due to adverse reactions
  • Among patients receiving FASLODEX plus placebo, 4% were reported to have permanently discontinued both FASLODEX and placebo, and 2% were reported to have discontinued placebo alone due to adverse reactions
  • Adverse reactions leading to treatment discontinuation of FASLODEX plus ribociclib (as compared to FASLODEX plus placebo) were ALT increased (5% vs 0%), AST increased (3% vs 0.6%), and vomiting (1% vs 0%)

Laboratory Abnormalities Occurring in ≥10% of Patients in MONALEESA-3

FASLODEX + ribociclib laboratory abnormalities
FASLODEX + ribociclib laboratory abnormalities
  • Among patients receiving FASLODEX plus ribociclib, 8% were reported to have permanently discontinued both FASLODEX and ribociclib, and 9% were reported to have discontinued ribociclib alone due to adverse reactions
  • Among patients receiving FASLODEX plus placebo, 4% were reported to have permanently discontinued both FASLODEX and placebo, and 2% were reported to have discontinued placebo alone due to adverse reactions
  • Adverse reactions leading to treatment discontinuation of FASLODEX plus ribociclib (as compared to FASLODEX plus placebo) were ALT increased (5% vs 0%), AST increased (3% vs 0.6%), and vomiting (1% vs 0%)

ALT=alanine aminotransferase; AST=aspartate aminotransferase.

 

*Infections; urinary tract infections; respiratory tract infections; gastroenteritis; sepsis (<1%).

 

References: 1. Slamon DJ, Neven P, Chia S, et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2–negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 2018;36(24):2465-2472. 2. 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. 3. FASLODEX® (fulvestrant) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.