A Study of Everolimus Plus Exemestane in Chinese Postmenopausal Women With Estrogen Receptor Positive, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Non-steroidal Aromatase Inhibitor (BOLERO-5)

Novartis

Status and phase: Completed; Phase 2

Conditions: Advanced Breast Cancer

Treatments: Drug: Exemestane; Drug: Everolimus; Drug: Everolimus Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03312738

CRAD001Y2202

Details and patient eligibility

About

This study aimed at evaluating the safety and efficacy of everolimus plus exemestane in Chinese postmenopausal women with ER+ HER2- locally advanced, recurrent, or metastatic breast cancer after recurrence or progression on letrozole or anastrozole.

Full description

This was a multicenter, double-blind, randomized, placebo-controlled, phase II study evaluating treatment with everolimus (10 mg daily) in combination with exemestane (25 mg daily) vs placebo in combination with exemestane (25 mg daily) in Chinese postmenopausal women with locally advanced, recurrent or metastatic ER+ HER2- breast cancer refractory to non-steroidal aromatase inhibitors.

Randomized participants started the study treatment at Cycle 1 Day 1, and were treated continuously until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from treatment for any other reason.

After end of treatment, all participants were followed up for safety up to 30 days after last dose of study treatment (exemestane and/or everolimus/placebo). All participants were followed for survival status at least every 3 months after treatment discontinuation unless they discontinued due to death, consent withdrawal or lost to follow-up

If a participants permanently discontinued study treatment for reasons other than disease progression, death, lost to follow-up, or withdrawal of consent to efficacy follow-up then they entered the post-treatment efficacy follow-up period until disease progression, death, lost to follow-up or withdrawal of consent for efficacy follow-up.

Enrollment: 159 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Chinese Postmenopausal women with ER+ HER2- locally advanced, recurrent, or metastatic breast cancer. Locally advanced breast cancer must not be amenable to curative treatment by surgery or radiotherapy.

• Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer

• Postmenopausal women. Postmenopausal status was defined either by:

  • Prior bilateral oophorectomy
  • Or age ≥60
  • Or age < 60 and amenorrhea for 12 or more months

• Recurrence or progression on prior NSAI was defined as:

  • Recurrence while on, or within one year (12 months) of end of adjuvant treatment with letrozole or anastrozole
  • Or Progression while on or within one month (30 days) of the end of prior treatment with letrozole or anastrozole

• Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment

• Patient had as per RECIST 1.1

  • measurable disease or non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
  • non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.

• Patient was able to swallow and retain oral medication

• Patient met the hematologic and biochemistery laboratory values at the screening visit

• Patient had a WHO performance status ≤2

• Written informed consent obtained prior to any screening procedures

Exclusion Criteria:

• HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive), based on the most recent test.
• Patients who had received more than one chemotherapy line for ABC
• Patients with symptomatic visceral disease and candidates to chemotherapy
• Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis (e.g. pleural effusion, ascites etc.)
• Patients receiving concomitant immunosuppressive agents or chronic corticosteroids used at the time of study entry except topical applications, inhaled sprays, eye drops or local injections.
• Uncontrolled diabetes mellitus as defined by HbA1c >7% despite adequate therapy.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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159 participants in 2 patient groups

Everolimus + Exemestane

Experimental group

Description:

Participants received everolimus as a continuous oral daily dose of 10 mg and exemestane as a continuous oral daily dose of 25 mg

Treatment:

Drug: Everolimus

Drug: Exemestane

Placebo + Exemestane

Active Comparator group

Description:

Participants received placebo as a continuous oral daily dose and exemestane as a continuous oral daily dose of 25 mg

Treatment:

Drug: Everolimus Placebo

Drug: Exemestane