A Phase 2 interventional study of Everolimus and Exemestane in Advanced Breast Cancer, sponsored by Novartis Pharmaceuticals. Completed at 15 sites in China. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-01-23.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 2, Interventional, and Treatment
Among 78 studies testing everolimus in Breast Neoplasms — 7 open to participants now, 10 under way, 6 of them phase 3. Everolimus · Breast Neoplasms.
Among the 78 studies testing everolimus in Breast Neoplasms, this one is the 22nd largest by enrollment, is one of 3 that started in 2017, is one of 40 in phase 2, and was the 68th registered.
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's enrollment of 159 is above the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →7 of the 78 studies testing everolimus in Breast Neoplasms are open now, in 12 countries. Each count lists the studies.
Everolimus: first FDA approval 2009 (AFINITOR), first EMA approval 2009. What it is approved for, and how studies give it, is on its page →
Of the 2,400 Breast Neoplasms studies recruiting now, 1,572 (66%) set no upper age limit and 591 (25%) stop at 75 or younger; 103 take children under 18; 214 take healthy volunteers.
This study: 18 Years and older · female · no healthy volunteers.
The full table on the hub →78 studies; the count open now beside each. This study's row is marked.
First in 2005; this study’s year is marked. 3 started in 2017.
Median enrollment 55 across the 78 interventional studies. Of the 57 that completed or were terminated, 35 (61%) have results posted.
17 of 78 have an industry lead sponsor. The 10 most frequent:
Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
178 studies in Breast Neoplasms by Novartis Pharmaceuticals: 18 open now, 32 under way, 4 of them phase 3. Of 141 finished, 66 (47%) have results posted.
Among the 178 studies in Breast Neoplasms by Novartis Pharmaceuticals, this one is the 61st largest by enrollment of the 141 interventional ones, is one of 6 that started in 2017, is one of 35 in phase 2, and was the 116th registered.
Novartis Pharmaceuticals’s Breast Neoplasms studies by the year they started, since 1998.
2 of the studies testing everolimus in Breast Neoplasms that are under way reach primary completion within a year, 2 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT07062965Phase 3PfizerA Study to Learn About the Study Medicine Called PF-07248144 in Combination With Fulvestrant in People With HR-positive, HER2-negative Advanced or Metastatic Breast Cancer Who Progressed After a Prior Line of Treatment. | 2027-07-22 |
| NCT06382948Phase 3MedSIRElacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i. | 2027-09 |
Among the 78 studies testing everolimus in Breast Neoplasms, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among Novartis Pharmaceuticals’s 178 in Breast Neoplasms:
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.
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.
Key Inclusion Criteria:
Postmenopausal women. Postmenopausal status was defined either by:
Recurrence or progression on prior NSAI was defined as:
Patient had as per 1.1
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants received everolimus as a continuous oral daily dose of 10 mg and exemestane as a continuous oral daily dose of 25 mg
Drug: Everolimus · Drug: Exemestane
Participants received placebo as a continuous oral daily dose and exemestane as a continuous oral daily dose of 25 mg
Drug: Exemestane · Drug: Everolimus Placebo
Everolimus was formulated as tablets of 5 mg strength and was packaged into blister packs . Everolimus (two 5 mg tablets daily) was administered in a blinded manner by continuous oral daily dosing.
Also known as: RAD001
Commercially available exemestane was supplied as 25 mg tablets. Exemestane was administered as continuous oral daily dose of 25 mg tablets.
Placebo was formulated to be indistinguishable from the everolimus tablets. Matching placebo (two tablets daily) was administered in a blinded manner by continuous oral daily dosing.
Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessment
PFS was defined as time from the date of randomization to the date of first documented progression or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. Disease progression was assessed using the local investigator's tumor assessment per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. The distribution of PFS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of PFS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
Time frame: From randomization up to date of first documented progression or death, assessed up to approximately 3.5 years
Progression-free Survival (PFS) Based on Blinded Independent Review Committee (BIRC) Assessment
PFS was defined as time from the date of randomization to the date of first documented progression or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. Disease progression was assessed using the BIRC tumor assessment per RECIST 1.1. The distribution of PFS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of PFS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
Time frame: From randomization up to date of first documented progression or death, assessed up to approximately 1.8 years
Overall Survival (OS)
OS was defined as the time from date of randomization to date of death due to any cause. If the participant was alive at the date of the analysis cut-off or lost to follow-up, then OS was censored at the last contact date prior to data cutoff date. The distribution of OS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of OS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
Time frame: From randomization to date of death, up to approximately 3.8 years
Overall Response Rate (ORR) Based on Local Radiology Review of Tumor Assessment
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR) according to RECIST using local radiologist's/investigator's tumor assessment. ORR was estimated and the exact binomial 90% CI was reported by treatment arm. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to approximately 3.5 years
Overall Response Rate (ORR) Based on BIRC Assessment
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR) according to RECIST using BIRC assessment. ORR was estimated and the exact binomial 90% CI was reported by treatment arm. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to approximately 1.8 years
Clinical Benefit Rate (CBR) Based on Local Radiology Review of Tumor Assessment
CBR was defined as the percentage of patients with best overall response of CR, PR or an overall lesion response of stable disease (SD) or Non-CR/Non-progressive disease with duration of 24 weeks or longer according to RECIST 1.1 using local radiologist's/investigator's tumor assessment. CBR was estimated and the exact binomial 90% CI was reported by treatment arm. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Time frame: Up to approximately 3.5 years
Clinical Benefit Rate (CBR) Based on BIRC Assessment
CBR was defined as the percentage of patients with best overall response of CR, PR or an overall lesion response of stable disease (SD) or Non-CR/Non-progressive disease with duration of 24 weeks or longer according to RECIST 1.1 using BIRC assessment. CBR was estimated and the exact binomial 90% CI was reported by treatment arm. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Time frame: Up to approximately 1.8 years
Time to Response (TTR) Based on Local Radiology Review of Tumor Assessment
TTR was defined as the time between date of randomization until first documented response (CR or PR) according to RECIST 1.1 using local radiologist's/investigator's tumor assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to approximately 3.5 years
Time to Response (TTR) Based on BIRC Assessment
TTR was defined as the time between date of randomization until first documented response (CR or PR) according to RECIST 1.1 using BIRC assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to approximately 1.8 years
Duration of Response (DOR) Based on Local Radiology Review of Tumor Assessment
DOR was defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause, according to RECIST 1.1 using local radiologist's/investigator's tumor assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: From date of first documented response to date of first documented disease progression or death, assessed up to approximately 3.5 years
Duration of Response (DOR) Based on BIRC Assessment
DOR was defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause, according to RECIST 1.1 using BIRC assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: From date of first documented response to date of first documented disease progression or death, assessed up to approximately 1.8 years
Time to Definitive Deterioration of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score From Baseline
ECOG PS is a measure of functional status with scores ranging from 0 (fully active) to 5 (dead). Deterioration was considered definitive if no improvements in the ECOG PS status were observed after an instance of deterioration. Death was considered as worsening of the ECOG PS if it occurred close to the last assessment, where "close" is defined as twice the planned period between two assessments. Participants who died after more than twice the planned period between two assessments were censored at the date of their last assessment before the cut-off. Participants receiving any further anticancer therapy prior to definitive worsening were censored at their date of last assessment prior to start of therapy. Participants that had not worsened were censored at the date of last assessment prior to cut off. Time to definitive deterioration was estimated using the Kaplan-Meier method.
Time frame: From randomization up to definitive deterioration of the ECOG PS by one categotu of the score, assessed up to approximately 3.5 years
Everolimus Predose Concentration (Cmin)
Blood samples were collected to assess everolimus predose concentration (Cmin) at steady state at Cycle 1 Week 4 (any day during week 4). Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection. Everolimus concentrations were determined in the whole blood by a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The method has a lower limit of quantitation (LLOQ) of 0.3 ng/mL for everolimus. Values below the LLOQ were set to 0.
Time frame: Predose on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Everolimus Concentration at 2 Hours Post Dose (C2h)
Blood samples were collected to assess everolimus concentration at 2 hours post dose (C2h) at steady state at Cycle 1 Week 4 (any day during week 4) Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection. Everolimus concentrations were determined in the whole blood by a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The method has a LLOQ of 0.3 ng/mL for everolimus. Values below the LLOQ were set to 0.
Time frame: Two hours post everolimus administration on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Exemestane Predose Concentration (Cmin)
Blood samples were collected to assess exemestane predose concentration (Cmin) at steady state at Cycle 1 Week 4 (any day during week 4). Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection. Exemestane concentrations were determined in the whole blood by a liquid chromatography with LC-MS/MS method. The method has a LLOQ of 20 pg/mL for exemestane. Values below the LLOQ were set to 0.
Time frame: Predose of exemestane on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Exemestane Concentration at 2 Hours Post Dose (C2h)
Blood samples were collected to assess exemestane concentration at 2 hours post dose (C2h) at steady state at Cycle 1 Week 4 (any day during week 4) Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection. Exemestane concentrations were determined in the whole blood by a liquid chromatography with LC-MS/MS method. The method has a LLOQ of 20 pg/mL for exemestane. Values below the LLOQ were set to 0.
Time frame: Two hours post exemestane administration on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
Estradiol Levels After 4 Weeks of Study Treatment
Blood samples were collected to assess estradiol levels after 4 weeks of study treatment. Estradiol was determined in plasma using competitive immunoassay. The method has a LLOQ of 1.952 pg/mL for estradiol. Values below the LLOQ were set to 0.
Time frame: Baseline, and at Cycle 1 Week 4 prior to any study drug (each cycle is defined as 4 weeks)
Participants took part in 15 investigative sites in China
| Milestone | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Started | 80 | 79 |
| Completed | 0 | 0 |
| Not completed | 80 | 79 |
| Withdrew: Progressive disease | 58 | 67 |
| Withdrew: Patient/guardian decision | 13 | 5 |
| Withdrew: Adverse event | 5 | 3 |
| Withdrew: Protocol deviation | 2 | 0 |
| Withdrew: Technical problems | 0 | 1 |
| Withdrew: Physician decision | 2 | 3 |
PFS was defined as time from the date of randomization to the date of first documented progression or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. Disease progression was assessed using the local investigator's tumor assessment per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. The distribution of PFS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of PFS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
| Months | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessment | 7.4 (5.5 to 9.2) | 2.0 (1.9 to 3.6) |
PFS was defined as time from the date of randomization to the date of first documented progression or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. Disease progression was assessed using the BIRC tumor assessment per RECIST 1.1. The distribution of PFS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of PFS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
| Months | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Progression-free Survival (PFS) Based on Blinded Independent Review Committee (BIRC) Assessment | 7.4 (5.5 to 9.3) | 3.1 (1.9 to 3.7) |
OS was defined as the time from date of randomization to date of death due to any cause. If the participant was alive at the date of the analysis cut-off or lost to follow-up, then OS was censored at the last contact date prior to data cutoff date. The distribution of OS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of OS, along with 90% CI. As this was an estimation based approach, no p-value was provided.
| Months | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Overall Survival (OS) | 26.1 (20.2 to 33.7) | 22.7 (18.6 to 37.8) |
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR) according to RECIST using local radiologist's/investigator's tumor assessment. ORR was estimated and the exact binomial 90% CI was reported by treatment arm. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
| Percentage of participants | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Overall Response Rate (ORR) Based on Local Radiology Review of Tumor Assessment | 10.0 (5.1 to 17.3) | 2.5 (0.5 to 7.8) |
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR) according to RECIST using BIRC assessment. ORR was estimated and the exact binomial 90% CI was reported by treatment arm. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
| Percentage of participants | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Overall Response Rate (ORR) Based on BIRC Assessment | 8.8 (4.2 to 15.8) | 2.5 (0.5 to 7.8) |
CBR was defined as the percentage of patients with best overall response of CR, PR or an overall lesion response of stable disease (SD) or Non-CR/Non-progressive disease with duration of 24 weeks or longer according to RECIST 1.1 using local radiologist's/investigator's tumor assessment. CBR was estimated and the exact binomial 90% CI was reported by treatment arm. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
| Percentage of participants | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Clinical Benefit Rate (CBR) Based on Local Radiology Review of Tumor Assessment | 42.5 (33.1 to 52.3) | 16.5 (10.0 to 24.9) |
CBR was defined as the percentage of patients with best overall response of CR, PR or an overall lesion response of stable disease (SD) or Non-CR/Non-progressive disease with duration of 24 weeks or longer according to RECIST 1.1 using BIRC assessment. CBR was estimated and the exact binomial 90% CI was reported by treatment arm. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
| Percentage of participants | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Clinical Benefit Rate (CBR) Based on BIRC Assessment | 31.3 (22.7 to 40.8) | 11.4 (6.1 to 19.0) |
TTR was defined as the time between date of randomization until first documented response (CR or PR) according to RECIST 1.1 using local radiologist's/investigator's tumor assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
| Days | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Time to Response (TTR) Based on Local Radiology Review of Tumor Assessment | 84.5 (51 to 162) | 53.0 (52 to 54) |
TTR was defined as the time between date of randomization until first documented response (CR or PR) according to RECIST 1.1 using BIRC assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
| Days | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Time to Response (TTR) Based on BIRC Assessment | 57.0 (15 to 224) | 81.5 (52 to 111) |
DOR was defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause, according to RECIST 1.1 using local radiologist's/investigator's tumor assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
| Days | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Duration of Response (DOR) Based on Local Radiology Review of Tumor Assessment | 243.5 (110 to 624) | 561.5 (282 to 841) |
DOR was defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause, according to RECIST 1.1 using BIRC assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
| Days | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Duration of Response (DOR) Based on BIRC Assessment | 148.0 (57 to 281) | 279.0 (221 to 337) |
ECOG PS is a measure of functional status with scores ranging from 0 (fully active) to 5 (dead). Deterioration was considered definitive if no improvements in the ECOG PS status were observed after an instance of deterioration. Death was considered as worsening of the ECOG PS if it occurred close to the last assessment, where "close" is defined as twice the planned period between two assessments. Participants who died after more than twice the planned period between two assessments were censored at the date of their last assessment before the cut-off. Participants receiving any further anticancer therapy prior to definitive worsening were censored at their date of last assessment prior to start of therapy. Participants that had not worsened were censored at the date of last assessment prior to cut off. Time to definitive deterioration was estimated using the Kaplan-Meier method.
| Months | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Time to Definitive Deterioration of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score From Baseline | NA (NA to NA) | NA (NA to NA) |
Blood samples were collected to assess everolimus predose concentration (Cmin) at steady state at Cycle 1 Week 4 (any day during week 4). Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection. Everolimus concentrations were determined in the whole blood by a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The method has a lower limit of quantitation (LLOQ) of 0.3 ng/mL for everolimus. Values below the LLOQ were set to 0.
| nanogram/mililiter (ng/mL) | Everolimus + Exemestane |
|---|---|
| Everolimus Predose Concentration (Cmin) | 16.5 ± 59.1 |
Blood samples were collected to assess everolimus concentration at 2 hours post dose (C2h) at steady state at Cycle 1 Week 4 (any day during week 4) Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection. Everolimus concentrations were determined in the whole blood by a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The method has a LLOQ of 0.3 ng/mL for everolimus. Values below the LLOQ were set to 0.
| ng/mL | Everolimus + Exemestane |
|---|---|
| Everolimus Concentration at 2 Hours Post Dose (C2h) | 44.2 ± 57.8 |
Blood samples were collected to assess exemestane predose concentration (Cmin) at steady state at Cycle 1 Week 4 (any day during week 4). Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection. Exemestane concentrations were determined in the whole blood by a liquid chromatography with LC-MS/MS method. The method has a LLOQ of 20 pg/mL for exemestane. Values below the LLOQ were set to 0.
| picogram/mililiter (pg/mL) | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Exemestane Predose Concentration (Cmin) | 737 ± 74.2 | 502 ± 48.7 |
Blood samples were collected to assess exemestane concentration at 2 hours post dose (C2h) at steady state at Cycle 1 Week 4 (any day during week 4) Steady-state was defined as having no dose adjustment/interruption of everolimus and exemestane in the previous 4 days prior to the day of the pre-dose PK sample collection. Exemestane concentrations were determined in the whole blood by a liquid chromatography with LC-MS/MS method. The method has a LLOQ of 20 pg/mL for exemestane. Values below the LLOQ were set to 0.
| pg/mL | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Exemestane Concentration at 2 Hours Post Dose (C2h) | 20500 ± 97.1 | 14300 ± 71.6 |
Blood samples were collected to assess estradiol levels after 4 weeks of study treatment. Estradiol was determined in plasma using competitive immunoassay. The method has a LLOQ of 1.952 pg/mL for estradiol. Values below the LLOQ were set to 0.
| pg/mL | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| Baseline | 5.98 ± 10.5 | 5.38 ± 10.4 |
| Week 4 | 3.98 ± 7.77 | 3.77 ± 6.80 |
On-treatment deaths were collected from first dose of study medication to 30 days after the last dose of study medication for a maximum duration of approximately 3.5 years Post-treatment survival follow-up deaths were collected after 30 days post-treatment, for a maximum duration of approximately 3.8 years All deaths refer to the sum of on-treatment and post-treatment deaths
| Participants | Everolimus + Exemestane | Placebo + Exemestane |
|---|---|---|
| On-treatment deaths | 3 | 2 |
| Post-treatment survival follow-up deaths | 41 | 43 |
| All deaths | 44 | 45 |
Collected over Adverse events were collected from first dose of study treatment to 30 days after last dose of study medication (on-treatment), up to approx. 3.5 years. Deaths were collected in the post treatment survival follow up from 31 days after last dose of study medication until the end of the study, up to approx. 3.8 years. These are not considered AEs. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Everolimus + Exemestane (On-treatment) | 3/80 (3.8%) | 18/80 (22.5%) | 79/80 (98.8%) |
| Placebo + Exemestane (On-treatment) | 2/79 (2.5%) | 10/79 (12.7%) | 62/79 (78.5%) |
| Everolimus + Exemestane (Post-treatment Survival Follow-up) | 41/73 (56.2%) | — | — |
| Placebo + Exemestane (Post-treatment Survival Follow-up) | 43/75 (57.3%) | — | — |
| Event | Everolimus + Exemestane (On-treatment) | Placebo + Exemestane (On-treatment) | Everolimus + Exemestane (Post-treatment Survival Follow-up) | Placebo + Exemestane (Post-treatment Survival Follow-up) |
|---|---|---|---|---|
| PneumoniaInfections and infestations | 6/80 | 0/79 | — | — |
| Bone painMusculoskeletal and connective tissue disorders | 0/80 | 2/79 | — | — |
| Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders | 2/80 | 0/79 | — | — |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/80 | 1/79 | — | — |
| CholecystitisHepatobiliary disorders | 0/80 | 1/79 | — | — |
| Hepatic function abnormalHepatobiliary disorders | 0/80 | 1/79 | — | — |
| Pain in extremityMusculoskeletal and connective tissue disorders | 0/80 | 1/79 | — | — |
| Pathological fractureMusculoskeletal and connective tissue disorders | 0/80 | 1/79 | — | — |
| CoughRespiratory, thoracic and mediastinal disorders | 1/80 | 1/79 | — | — |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 0/80 | 1/79 | — | — |
| Event | Everolimus + Exemestane (On-treatment) | Placebo + Exemestane (On-treatment) | Everolimus + Exemestane (Post-treatment Survival Follow-up) | Placebo + Exemestane (Post-treatment Survival Follow-up) |
|---|---|---|---|---|
| Aspartate aminotransferase increasedInvestigations | 38/80 | 15/79 | — | — |
| HyperglycaemiaMetabolism and nutrition disorders | 36/80 | 6/79 | — | — |
| StomatitisGastrointestinal disorders | 28/80 | 5/79 | — | — |
| Alanine aminotransferase increasedInvestigations | 28/80 | 14/79 | — | — |
| AnaemiaBlood and lymphatic system disorders | 26/80 | 10/79 | — | — |
| Weight decreasedInvestigations | 23/80 | 3/79 | — | — |
| HypercholesterolaemiaMetabolism and nutrition disorders | 21/80 | 0/79 | — | — |
| Mouth ulcerationGastrointestinal disorders | 19/80 | 3/79 | — | — |
| Decreased appetiteMetabolism and nutrition disorders | 17/80 | 4/79 | — | — |
| White blood cell count decreasedInvestigations | 16/80 | 5/79 | — | — |
| Age, Continuous(Years) | Everolimus + Exemestane | Placebo + Exemestane | Total |
|---|---|---|---|
| Mean | 56.6 ± 9.14 | 56.3 ± 8.43 | 56.4 ± 8.77 |
| Sex: Female, Male(Participants) | Everolimus + Exemestane | Placebo + Exemestane | Total |
|---|---|---|---|
| Female | 80 | 79 | 159 |
| Male | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Everolimus + Exemestane | Placebo + Exemestane | Total |
|---|---|---|---|
| Asian | 80 | 79 | 159 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Ran from Sep 2017 to primary completion in Apr 2022, 55 months.
Results were first posted in Jan 2024, 1 year 8 months after primary completion.
Of 232 industry-sponsored phase 2 interventional studies under Breast Neoplasms, half reached primary completion within 34 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 53. This study's 55 months is above that.
Counting every sponsor, half of 1,302 studies reached it within 51 months; a quarter within 30 and three quarters within 82.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Apr 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Everolimus