Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication Monotherapy FASLODEX is indicated for the treatment of: • Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or • HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. FDA label
Also known as Standard Arm - Fulvestrant, Fulvestrant injection, Faslodex, ZD9238
Fulvestrant · 23 trials · 16 indications
Time to next treatment (TTNT1 is defined as the time from the date of first dose of capivasertib+fulvestrant until the first subsequent anti-cancer therapy after discontinuation of study treatment or death due to any cause).
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Participants who discontinue treatment prior to progression should continue to be scanned until progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s).
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Kaplan-Meier estimate was used.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause.
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause Kaplan-Meier estimate was used.
PFS was defined as the time from randomisation until objective disease progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), surgery or radiotherapy to manage worsening of disease or death by any cause (in the absence of progression). Outcome measure is reported as median time from randomisation to PFS, calculated using the Kaplan-Meier technique.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or unequivocal progression of existing non-target lesions, or the appearance of new lesions, or death (by any cause in the absence of progression). The primary analysis for PFS was the log rank test stratified by last endocrine therapy received prior to fulvestrant (AO vs. AI). The treatment effect was estimated using the HR of 500 mg fulvestrant to 250 mg fulvestrant together with the corresponding 95% CI and p value.
Median time (in months) from randomisation until objective disease progression or death (in the absence of objective progression).
Number of subjects with serum PSA reduction ≥ 50% at 3 months
Objective response rate was defined as percentage of patients with either complete response (CR - disappearance of all target lesions) or partial response (PR - at least 30% decrease in the sum of diameters of target lesions). All patients were to be followed up every 12 weeks for progression, defined by response evaluation criteria in solid tumors (RECIST v1.1).
Number of patients event-free
An objective response (OR) is defined as a patient having a best overall response of either complete response (CR) or partial response (PR). A patient has best overall response of CR if she had overall response of CR or PR on one visit and met the confirmation criteria per RECIST. ORR is defined as percentage of patients with objective response. Each patient with measurable disease at baseline was assessed for OR from the sequence of Response Evaluation Criteria in Solid Tumors (RECIST) scan data up to data cut-off. RECIST scans were performed every 12 weeks (+/- 2weeks) from randomization
A Clinical Benefit (CB) responder is defined as a patient having a best overall response of either complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks evaluated according to modified RECIST. The Clinical Benefit Rate is the percentage of patients with CB.
Vaginal bleeding days are defined as the number of days in which vaginal bleeding, (including spotting) occurred. In order to annualize, a 12-month period is defined as 360 days and a 6-month period is defined as 180 days. Frequency of annualized vaginal bleeding days = \[(number of vaginal bleeding days)/(total number of days of the time interval under consideration)\] multiplied by 360. Change in frequency is equal to the on-treatment frequency minus the baseline frequency. Diary cards will capture days of vaginal bleeding during the 12-month treatment period. Change in the frequency of annualized days of vaginal bleeding during the 12-month treatment period compared to the 6-month baseline period, based on a worst-case scenario calculation (ie, missing diary card days counted as bleeding days) are reported.
The percentage change in frequency is defined as 100% times the difference (the on-treatment period frequency minus the baseline period frequency), divided by the baseline period frequency. The percentage of participants with baseline vaginal bleeding days who experienced ≥ 50% reduction in the number of vaginal bleeding days during the 12 month treatment period compared to the 6 month baseline period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.
Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding days over a 6-month treatment period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.
Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding days over a 12-month treatment period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.
Change in rate of BA advancement over first 6-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in chronological age (CA) (years). Change in rate of increase in BA from baseline period to on-treatment period is defined as increase in BA divided by change in CA (in fractional years) between BA radiograph dates. It is calculated as \[(BA6 - BA0)/(CA6 - CA0)\] - \[(BA0 - BA\*)/(CA0 - CA\*)\], where 6, 0, \* stand for first Month 6 Visit, Month 0 Visit, and the 6-month retrospective visit, respectively.
Change in rate of BA advancement over second 6-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in CA (years). Change in rate of increase in BA from baseline period to on-treatment period is defined as increase in BA divided by change in CA (in fractional years) between the BA radiograph dates. It is calculated as \[(BA6 - BA0)/(CA6 - CA0)\] - \[(BA0 - BA\*)/(CA0 - CA\*)\], where 6, 0, \* stand for second Month 6 Visit, Month 0 Visit, and the 6-month retrospective visit, respectively.
Change in rate of BA advancement over whole 12-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in CA (years). Change in rate of increase in BA from baseline period to on-treatment period is defined as increase in BA divided by change in CA (in fractional years) between the BA radiograph dates. It is calculated as \[(BA12 - BA0) / (CA12 - CA0)\] - \[(BA0 - BA\*) / (CA0 - CA\*)\], where 12, 0, \* stand for Month 12 Visit, Month 0 Visit, and the 6-month retrospective visit, respectively.
Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to first 6-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.
Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to second 6-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.
Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to the 12-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.
Change in growth velocity (Z-score) from baseline period to the first 6 months of treatment period is reported. The Z-score (also known as Standard Deviation Score \[SDS\]) is defined as \[(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by standard deviation (SD)\], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Z-score of 0 represents the population mean for growth velocity. For McCune-Albright Syndrome, Z-score below mean is a better outcome.
Change in growth velocity (Z-score) from baseline period to the second 6 months of treatment period is reported. The Z-score (also known as SDS) is defined as \[(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by SD\], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Z-score of 0 represents the population mean for growth velocity. For McCune-Albright Syndrome, Z-score below mean is a better outcome.
Change in growth velocity (Z-score) from baseline period to 12 months of treatment period is reported. The Z-score (also known as SDS) is defined as \[(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by SD)\], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Z-score of 0 represents the population mean for growth velocity. For McCune-Albright Syndrome, Z-score below mean is a better outcome.
Uterine volume was calculated via ultrasound using the formula: 0.5 multiplied by (longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated. Change in uterine volume from baseline to Month 6 was calculated as Month 6 volume (by ultrasound) minus screening visit volume (by ultrasound). Baseline (screening visit) is the pre-treatment baseline visit.
Uterine volume was calculated via ultrasound using the formula: 0.5 multiplied by (longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated. Change in uterine volume from Month 6 to Month 12/final visit was calculated as Month 12/finial visit volume (by ultrasound) minus Month 6 volume (by ultrasound).
Uterine volume was calculated via ultrasound using the formula: 0.5 multiplied by (longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated. Change in uterine volume from baseline to Month 12/final visit was calculated as End of Study volume (by ultrasound) minus Screening Visit volume (by ultrasound). Baseline (screening visit) is the pre-treatment baseline visit.
The mean ovarian volume was the average of both ovaries. Average volume was calculated as 0.5 multiplied by (volume of left ovary plus volume of right ovary) if both volumes were calculated; otherwise, average ovarian volume was considered missing. The volume of each ovary was calculated via ultrasound using the formula: 0.5 multiplied by longitudinal dimension multiplied by anterior-posterior dimension multiplied by transverse dimension. Change in mean ovarian volume from baseline to Month 6 was calculated as Month 6 mean volume minus Screening Visit mean volume. Baseline (screening visit) is the pre-treatment baseline visit.
The mean ovarian volume was the average of both ovaries. Average volume was calculated as 0.5 multiplied by (volume of left ovary plus volume of right ovary) if both volumes were calculated; otherwise, average ovarian volume was considered missing. The volume of each ovary was calculated via ultrasound using the formula: 0.5 multiplied by longitudinal dimension multiplied by anterior-posterior dimension multiplied by transverse dimension. Change in mean ovarian volume from Month 6 to Month 12/final visit was calculated as Month 12/final visit mean volume minus Month 6 mean volume.
The mean ovarian volume was the average of both ovaries. Average ovarian volume was calculated as 0.5 multiplied by (volume of left ovary plus volume of right ovary) if both volumes were calculated; otherwise, average ovarian volume was considered missing. The volume of each ovary was calculated via ultrasound using the formula: 0.5 multiplied by longitudinal dimension multiplied by anterior-posterior dimension multiplied by transverse dimension. Change in mean ovarian volume from baseline to the end of the study was calculated as End of Study mean volume minus Screening Visit mean volume. Baseline (screening visit) is the pre-treatment baseline visit.
Mean clearance of fulvestrant is reported.
Total apparent volume of distribution (Vss/F) is the total apparent volume in the body into which Fulvestrant distributes at equilibrium. Vss/F = V1/F + V2/F. V1/F is the volume of the first compartment and V2/F is the volume of the second compartment. V1/F of fulvestrant is reported. The measure of variability presented is the inter-individual error.
Total apparent volume of distribution (Vss/F) is the total apparent volume in the body into which Fulvestrant distributes at equilibrium. Vss/F = V1/F + V2/F. V1/F is the volume of the first compartment and V2/F is the volume of the second compartment. V2/F of fulvestrant is reported. The measure of variability presented is the inter-individual error.
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Clinical laboratory parameter analysis included hematology and clinical chemistry.
Number of participants with compliance to study treatment are reported. Treatment compliance was ensured at each treatment visit whether each participant received all protocol-defined injections up until the point they either withdrew from the study or completed the main study period. Compliance with study treatment for each participant for the 12-month treatment period was calculated as total number of injections divided by number of visits between first injection (Month 0) and last injection (at Month 11).
Number of participants with withdrawals from study treatment due to TEAE are reported.
Serum oestradiol level at Month 12 (final visit) is reported.
Serum LH level collected at Month 12 (final visit) is reported.
Serum FSH level collected at Month 12 (final visit) is reported.
Serum testosterone level at Month 12 (final visit) is reported.
For each sample, the ER H-score is calculated from the percentage of cells staining very weak (+/-); weak (+); moderate (++); or strong (+++) as follows: H-score = \[(0.5 x percent +/-) + (1 x percent +) + (2 x percent ++) + (3 x percent +++)\]. Range 0-300. The greater the change from baseline (randomization) in ER H-score, the greater the blockage of ER expression and the greater the potential anti-tumour activity. Percentage change from baseline=\[(SRG - BL)/BL\]x100
For each sample, the PgR H-score is calculated from the percentage of cells staining very weak (+/-); weak (+); moderate (++); or strong (+++) as follows: H-score = \[(0.5 x percent+/-) + (1 x percent+) + (2 x percent++) + (3 x percent+++)\]. Range 0-300. The greater the change from baseline (randomization in PgR H-score, the greater the blockage of PgR expression and the greater the potential anti-tumour activity. Percentage change from baseline=\[(SRG - BL)/BL\]x100
For each sample, the Ki67 labelling index is calculated as the percentage of cells stained positive for Ki67. Range 0-100. The greater the change from baseline (randomization) in Ki67 labelling index, the greater the blockage of Ki67 expression and the greater the potential anti-tumour activity. Percentage change from baseline=\[(SRG - BL)/BL\]x100
Number of patients with Complete Remission (CR) and Partial Response (PR), as determined by an independent expert panel according to the WHO response criteria.
Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. ER expression
| Arm | Type | Description |
|---|---|---|
| Capivasertib + fulvestrant | EXPERIMENTAL | Fulvestrant: 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. Capivasertib: 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle. |
| Placebo + fulvestrant | PLACEBO_COMPARATOR | Fulvestrant: 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. Placebo: 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle. |
| faslodex+placebo | EXPERIMENTAL | Blinded: Fulvestrant 500mg intramuscular injection (2x250mg) plus dummy Anastrozole tablets |
| arimidex +placebo | ACTIVE_COMPARATOR | Blinded: Anastrozole 1mg tablets plus dummy Fulvestrant intramuscular injection (2x0mg) |
| Fulvestrant 500mg | EXPERIMENTAL | Fulvestrant 500mg (2 syringes of Fulvestrant 250mg), Fulvestrant 500 mg i.m. every 28 (+/- 3) days plus an additional 500 mg on day 14 (+/-3) of first month only |
| Fulvestrant 250mg | ACTIVE_COMPARATOR | Fulvestrant 250mg (1 syringe of fulvestrant 250mg + 1 syringe matching placebo), Fulvestrant 250 mg and matching placebo i.m. every 28 (+/- 3) days plus an additional 2 placebo syringes on day 14 (+/-3) of first month only |
| 1 | EXPERIMENTAL | fulvestrant and anastrozole |
| 2 | EXPERIMENTAL | fulvestrant and placebo |
| 3 | ACTIVE_COMPARATOR | exemestane alone |
| Fulvestrant | EXPERIMENTAL | - |
| Standard arm | ACTIVE_COMPARATOR | Fulvestrant, 500 mg |
| AZD9496 | EXPERIMENTAL | 250 mg bd taken orally for 5-14 days |
| Name | Type | Description |
|---|---|---|
| Fulvestrant | DRUG | 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. |
| Capivasertib | DRUG | 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle |
| Placebo | DRUG | Placebo to match 400 mg BD (2 tablets of placebo to match 200 mg taken twice daily = placebo to match total daily dose of 800 mg) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle |
| faslodex 500mg | DRUG | 2 x intramuscular injections at day 1, 14, 28 and every 28 days thereafter |
| arimidex 1mg | DRUG | oral tablet 1 daily |
| faslodex dummy | DRUG | 2 x intramuscular injections at day 1, 14, 28 and every 28 days thereafter |
| arimidex dummy | DRUG | oral tablet 1 daily |
| anastrozole | DRUG | Tablet, oral, once daily until disease progression. |
| exemestane | DRUG | Tablet, oral, once daily until disease progression. |
| Tamoxifen | DRUG | 20 mg oral tablet |
| Anastrazole | DRUG | oral tablet |
| Standard Arm - Fulvestrant | DRUG | 500 mg Fulvestrant administered as two consecutive 5 ml intramuscular injections on Day 1, one in each buttock |
| AZD9496 | DRUG | Administered at 250 mg bd orally for 5-14 days commencing on Day 1, and continuing up to the day of biopsy |
Key Inclusion Criteria Histologically confirmed HR+/HER2- breast cancer (primary or metastatic): * HR+ defined as ER+ with or without PRg+ * HER2- defined as IHC 0 or 1+, or IHC 2+/ISH- Patient with tumours harbouring at least one PIK3CA/AKT1/PTEN qualifying alteration detected by a validated tes...
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Fulvestrant is used to treat advanced breast cancer, including locally advanced (inoperable) or metastatic breast cancer, and breast neoplasms. It is also being studied in endometrial carcinoma. It is an oncology drug developed by AstraZeneca PLC and is given as an injection.
Fulvestrant targets ESR1, the estrogen receptor, and acts as an antagonist. By binding and blocking this receptor, it interferes with estrogen-driven signaling in breast cancer cells. This target class and mechanism underlie its use in hormone receptor positive breast cancer, including HR+/HER2- disease.
Fulvestrant is developed by AstraZeneca PLC, which trades under the ticker AZN. The company sponsors the clinical trial program evaluating fulvestrant in breast cancer, including combination studies with capivasertib and comparisons against other endocrine therapies.
Fulvestrant is in Phase 3 clinical development. It is an investigational small molecule studied in controlled, randomized, double-blind trials, with biomarker-selected patient populations. Seven trials are listed in its program, of which six are completed and one is active but not recruiting.
Fulvestrant trials include NCT06764186, a Phase 3b study of capivasertib plus fulvestrant in advanced breast cancer in Spain, and NCT04305496, a Phase 3 trial of capivasertib plus fulvestrant versus placebo plus fulvestrant in HR+/HER2- breast cancer. Other studies include NCT03236974 and NCT01300351.
Yes. Fulvestrant is also known as Fulvestrant injection, Standard Arm - Fulvestrant, and Standard Arm- Fulvestrant. These names refer to the same AstraZeneca drug, which is administered as an injection and studied across breast cancer and endometrial carcinoma indications.