Study of Efficacy and Safety in Premenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer (MONALEESA-7)

Novartis

Status and phase: Completed; Phase 3

Conditions: Advanced Metastatic Breast Cancer

Treatments: Drug: Tamoxifen; Drug: Ribociclib; Drug: Goserelin; Drug: Letrozole; Drug: Anastrozole; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02278120

2014-001931-36 (EudraCT Number)

CLEE011E2301

Details and patient eligibility

About

The purpose of this study was to determine whether treatment with tamoxifen or a non-steroidal aromatase inhibitors (NSAI) + goserelin + LEE011 prolonged progression-free survival (PFS) compared to treatment with tamoxifen or a NSAI + goserelin + placebo in premenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer.

Full description

This was a randomized, Phase III, double-blind, global study comparing the treatment efficacy and safety of ribociclib + goserelin + tamoxifen or a NSAI (letrozole or anastrozole) versus placebo + goserelin + tamoxifen or a NSAI in premenopausal women with HR+, HER2- advanced breast cancer.

Eligible participants were randomized in a 1:1 ratio to either the ribociclib arm or the placebo arm. Study treatment continued until disease progression, unacceptable toxicity, death, or discontinuation for any other reason.

Participants who discontinued treatment due to reasons other than disease progression or withdrawal of consent for efficacy follow-up continued to be monitored until disease progression, death, withdrawal of consent, loss to follow-up, or subject/guardian decision (post-treatment efficacy follow-up).

All participants who discontinued treatment were followed for survival until the predetermined number of overall survival (OS) events was reached.

Following the final OS analysis (performed when approximately 189 deaths were recorded) and with protocol amendment 6 (dated 18-Jul-2019), participants and investigators were unblinded and those participants in the placebo arm had the opportunity to cross-over to the ribociclib arm to receive ribociclib + goserelin + NSAI. Cross-over was optional and was conducted at the investigator's discretion and upon participant consent.

Enrollment: 672 patients

Sex: Female

Ages: 18 to 59 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key inclusion criteria:

• Patients had advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy
• Patients were premenopausal or perimenopausal at the time of study entry
• Patients who had received (neo) adjuvant therapy for breast cancer were eligible
• Patients had a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer
• Patients had HER2-negative breast cancer
• Patients must have either had measurable disease or If no measurable disease was present, then at least one predominantly lytic bone lesion
• Patients had an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Patients had adequate bone marrow and organ function

Key exclusion criteria:

• Patients who had received a prior CDK4/6 inhibitor
• Patients were postmenopausal
• Patients who currently had inflammatory breast cancer at screening.
• Patients who had received any prior hormonal anti-cancer therapy for advanced breast cancer, except for ≤ 14 days of tamoxifen or NSAI ± goserelin for advanced breast cancer prior to randomization.
• Patients had a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated basal cell skin carcinoma, squamous cell skin carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• Patients with CNS metastases.
• Patients had active cardiac disease or a history of cardiac dysfunction
• Patients were currently using other antineoplastic agents
• Patients were pregnant or nursing or physiologically capable of becoming pregnant and not using highly effective contraception.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

672 participants in 2 patient groups, including a placebo group

Ribociclib + NSAI/tamoxifen + goserelin

Experimental group

Description:

Ribociclib 600 mg daily oral (3 weeks on/ 1 week off) in combination with NSAI or tamoxifen (tamoxifen 20 mg daily oral or letrozole 2.5 mg daily oral or anastrozole 1 mg daily oral) and goserelin 3.6 mg subcutaneous injection (once every 28 days)

Treatment:

Drug: Ribociclib

Drug: Tamoxifen

Drug: Anastrozole

Drug: Goserelin

Drug: Letrozole

Placebo + NSAI/tamoxifen + goserelin

Placebo Comparator group

Description:

Placebo daily oral (3 weeks on/ 1 week off) in combination with NSAI or tamoxifen (tamoxifen 20 mg daily oral or letrozole 2.5 mg daily oral or anastrozole 1 mg daily oral) and goserelin 3.6 mg subcutaneous injection (once every 28 days). Participants were unblinded once the final OS analysis was conducted and after the implementation of protocol amendment 6 (16-Jul-2019) and were given the option to crossover to treatment with ribociclib +NSAI/tamoxifen + goserelin.

Treatment:

Drug: Tamoxifen

Drug: Anastrozole

Drug: Placebo

Drug: Goserelin

Drug: Letrozole