Drug Trials Snapshots: ORSERDU
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the ORSERDU Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
ORSERDU (elacestrant)
or-SER-doo
Stemline Therapeutics, Inc
Approval date: January 27, 2023
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ORSERDU is a drug for the treatment of postmenopausal females and adult males with a specific form of advanced breast cancer that progressed after previous treatment with endocrine therapy.
It is to be used in patients whose cancer:
- is estrogen receptor (ER)-positive
- is human epidermal growth factor receptor 2 (HER2)-negative
- contains an abnormal (mutated) ESR1 gene, and
- is advanced or has spread to other parts of the body (metastatic)
How is this drug used?
ORSERDU is a tablet. It is taken orally once daily with food.
Who participated in the clinical trials?
The FDA approved ORSERDU based primarily on evidence from one clinical trial (NCT03778931) of 478 patients with ER-positive, HER2-negative, advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Of these 478 patients, 228 had ESR1 mutations (efficacy population). The safety population consisted of 467 patients who received at least one dose of clinical trial drug. The trial was conducted in 150 sites in 17 countries across Asia, Australia, Canada, Europe, Latin America, and the United States.
How were the trials designed?
The benefit and side effects of ORSERDU were evaluated in postmenopausal females and adult males with advanced or metastatic ER-positive, HER2-negative breast cancer that had progressed following treatment with endocrine therapy. About half of the patients enrolled in the clinical trial had an abnormal (mutated) ESR1 gene.
Patients received either ORSERDU as a tablet by mouth daily or a standard of care treatment consisting of either fulvestrant or an aromatase inhibitor, which was decided by their oncologist. The treatment continued until their disease progressed or the side effects became too toxic.
The benefit was assessed by measuring the length of time tumors did not grow after treatment (progression-free survival [PFS]).
How were the trials designed?
The efficacy and safety of ORSERDU were evaluated in one clinical trial.
The trial was a randomized, open-label, active-controlled, multicenter trial evaluating ORSERDU in 478 postmenopausal females and adult males with ER-positive, HER2 negative advanced or metastatic breast cancer of which 228 patients had ESR1 mutations (efficacy population). The safety population consisted of 467 patients who received at least one dose of trial drug. Patients were required to have disease progression on one or two prior lines of endocrine therapy, including one line containing a CDK4/6 inhibitor. ESR1 mutational status was determined by blood circulating tumor deoxyribonucleic acid (ctDNA) using the Guardant360 CDx assay.
Patients were randomized to receive ORSERDU or investigator’s choice of endocrine therapy (fulvestrant or an aromatase inhibitor). Patients were treated until disease progression or unacceptable toxicity.
The primary efficacy endpoint was PFS determined by a blinded imaging review committee (BIRC). An additional efficacy outcome measure was overall survival (OS).
DEMOGRAPHICS SNAPSHOT
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2. Baseline Demographics by Race1,2
Source: Adapted from FDA Review
1 Patients could select more than one race.
2 Missing information from patients on race.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1 summarizes the demographics of patients in the clinical trial.
Table 1. Demographics of the Safety Population
|
Demographic |
ORSERDU |
Fulvestrant or an |
|---|---|---|
|
Age group, years |
||
|
<65 |
134 (56.5) |
120 (52.2) |
|
≥65 |
103 (43.5) |
110 (47.8) |
|
Race1,2 |
||
|
Asian |
16 (8.5) |
15 (8.1) |
|
Black or African American |
5 (2.6) |
8 (4.3) |
|
White |
167 (88.4) |
162 (87.1) |
|
Other |
1 (0.5) |
1 (0.5) |
|
Gender |
||
|
Female |
231 (97.5) |
229 (99.6) |
|
Male |
6 (2.5) |
1 (0.4) |
|
Ethnicity |
||
|
Hispanic or Latino |
19 (8) |
17 (7.4) |
|
Not Hispanic or Latino |
193 (81.4) |
184 (80 |
|
Unknown |
25 (10.5) |
29 (12.6) |
Source: Adapted from FDA Review
1 Patients may select more than one race.
2 Missing information from patients on race.
What are the benefits of this drug?
In patients with an abnormal (mutated) ESR1 gene, those who received ORSERDU experienced a longer period without tumor growth compared to those who received fulvestrant or an aromatase inhibitor.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 summarizes efficacy results based on PFS by BIRC and OS.
Table 2. Efficacy Results (Patients With ESR1 Mutations)
|
Parameter |
ORSERDU |
Fulvestrant or an |
|---|---|---|
|
Progression-free survivala |
||
|
Number of PFS events, n (%) |
62 (54) |
78 (69) |
|
Median PFS monthsb (95% CI) |
3.8 (2.2, 7.3) |
1.9 (1.9, 2.1) |
|
Hazard ratioc (95% CI) |
0.55 (0.39, 0.77) |
|
|
p-valued |
0.0005 |
|
|
Overall survival |
||
|
Number of OS events, n (%) |
61 (53) |
60 (53) |
|
Hazard ratioc (95% CI) |
0.90 (0.63, 1.30) |
|
|
p-valued |
NS |
|
Source: ORSERDU Prescribing Information
a PFS results based on BIRC.
b Kaplan-Meier estimate; 95% CI based on the Brookmeyer-Crowley method using a linear transformation.
c Cox proportional hazards model stratified by prior treatment with fulvestrant (yes vs no) and visceral metastasis (yes vs no).
d Stratified log-rank test two-sided p-value.
Abbreviations: CI, confidence interval; ESR1, estrogen receptor 1; NS, not statistically significant; OS, overall survival; PFS, progression-free survival
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: All patients in the clinical trial with an ESR1 mutation were female; therefore, differences in how ORSERDU worked among sex could not be determined.
- Race: The majority of patients in the clinical trial were White. The number of patients in other races was limited; therefore, differences in how ORSERDU worked among races could not be determined.
- Age: ORSERDU worked similarly in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3 shows the efficacy results by demographic and geographic subgroups based on PFS in patients with ESR1 mutations.
Table 3. PFS per Blinded Imaging Review Committee in Different Subgroups (Patients With ESR1 Mutations)
|
Subgroup |
N |
HR |
CI |
|---|---|---|---|
|
Race1,2 |
|||
|
White |
164 |
0.404 |
0.267, 0.606 |
|
Asian |
13 |
0.891 |
0.122, 4.652 |
|
Other |
9 |
0.289 |
0.040, 1.503 |
|
Age, years |
|||
|
<65 |
124 |
0.572 |
0.363, 0.898 |
|
≥65 |
104 |
0.499 |
0.295, 0.831 |
|
Geographic region |
|||
|
Europe |
113 |
0.624 |
0.386, 1.011 |
|
North America |
75 |
0.410 |
0.221, 0.736 |
|
Asia |
26 |
0.552 |
0.149, 1.678 |
Source: Adapted from FDA Review
1 Patients could select more than one race.
2 Missing information from patients on race.
Abbreviations: CI, confidence interval; ESR1, estrogen receptor 1; HR, hazard ratio; PFS, progression-free survival
What are the possible side effects?
ORSERDU may cause serious side effects, including increased fat (lipid) levels in your blood (hypercholesterolemia and hypertriglyceridemia) as well as harm to a fetus.
The most common side effects of ORSERDU include muscle and joint (musculoskeletal) pain, nausea, increased cholesterol and triglyceride levels in your blood, increased liver enzymes, tiredness, decreased hemoglobin, vomiting, decreased sodium levels in your blood, increased blood creatinine level, decreased appetite, diarrhea, headache, constipation, stomach-area (abdominal) pain, hot flush, and heartburn or indigestion.
What are the possible side effects (results of trials used to assess safety)?
Table 4 summarizes common adverse reactions based on the safety population of patients with ER-positive, HER2-negative advanced or metastatic breast cancer who received at least one dose of trial drug.
Table 4. Adverse Reactions (≥10%) in Patients With ER-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer Who Received ORSERDU in EMERALDa
|
Adverse Reaction |
ORSERDU |
Fulvestrant or an |
||
|---|---|---|---|---|
|
All Grades |
Grade 3 or 4c |
All Grades |
Grade 3 or 4c |
|
|
Musculoskeletal and connective tissue disorders |
||||
|
Musculoskeletal painb |
41 |
7 |
39 |
1 |
|
Gastrointestinal disorders |
||||
|
Nausea |
35 |
2.5 |
19 |
0.9 |
|
Vomitingb |
19 |
0.8 |
9 |
0 |
|
Diarrhea |
13 |
0 |
10 |
1 |
|
Constipation |
12 |
0 |
6 |
0 |
|
Abdominal painb |
11 |
1 |
10 |
0.9 |
|
Dyspepsia |
10 |
0 |
2.6 |
0 |
|
General disorders |
||||
|
Fatigueb |
26 |
2 |
27 |
1 |
|
Metabolism and nutrition disorders |
||||
|
Decreased appetite |
15 |
0.8 |
10 |
0.4 |
|
Nervous system |
||||
|
Headache |
12 |
2 |
12 |
0 |
|
Vascular disorders |
||||
|
Hot flush |
11 |
0 |
8 |
0 |
Source: ORSERDU Prescribing Information
a Adverse reactions were graded using NCI CTCAE version 5.0.
b Includes other related terms
c Only includes Grade 3 adverse reactions.
Clinically relevant adverse reactions in < 10% of patients who received ORSERDU included rash, insomnia, dyspnea, cough, dizziness, stomatitis and gastroesophageal reflux disease.
Abbreviations: ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events
Table 5 summarizes laboratory abnormalities.
Table 5. Select Laboratory Abnormalities (≥10%) That Worsened From Baseline in Patients With ER-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer a
|
Laboratory Abnormality |
ORSERDUa |
Fulvestrant or an |
||
|---|---|---|---|---|
|
All Grades |
Grade 3 or 4 |
All Grades |
Grade 3 or 4 |
|
|
Chemistry |
||||
|
Cholesterol increased |
30 |
1 |
17 |
0 |
|
Aspartate aminotransferase increased |
29 |
0 |
34 |
1 |
|
Triglycerides increased |
27 |
2 |
15 |
1 |
|
Alanine aminotransferase increased |
17 |
0 |
24 |
1 |
|
Sodium decreased |
16 |
1 |
15 |
0 |
|
Creatinine increased |
16 |
0 |
6 |
0 |
|
Hematology |
||||
|
Hemoglobin decreased |
26 |
1 |
20 |
2 |
Source: ORSERDU Prescribing Information
a The denominator used to calculate the rate varied from 29 to 236 for ORSERDU and from 37 to 225 for fulvestrant or an aromatase inhibitor based on the number of patients with a baseline value and at least one post-treatment value.
Abbreviations: ER, estrogen receptor; HER2, human epidermal growth factor receptor 2
Were there any differences in side effects of the clinical trials among sex, race, and age?
- Sex: The majority of patients in the clinical trial were female; therefore, differences in the occurrence of side effects among sex could not be determined.
- Race: The majority of patients were White. The number of patients in other races was limited; therefore, differences in the occurrence of side effects among other races could not be determined.
- Age: The incidence of overall side effects was similar in patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Analysis of side effects by subgroup was limited to age since nearly all of patients in the trial were female and the vast majority were White. Table 6 summarizes all treatment-emergent adverse events (TEAEs) and grade 3 to 4 TEAEs by age subgroup.
Table 6. Summary of Treatment-Emergent Adverse Events by Age
|
Parameter |
|
Fulvestrant or an |
||
|---|---|---|---|---|
|
<65 Years |
≥65 Years |
<65 Years |
≥65 Years |
|
|
Any TEAEs1 |
122 (91) |
96 (93.2) |
101 (84.2) |
97 (88.2) |
|
Grade 3 or 4 TEAEs2 |
41 (31) |
21 (20) |
25 (21) |
22 (20) |
Source: Adapted from FDA Review
1 Number of patients with at least one TEAE
2 Any treatment-related CTCAE grade 3 and grade 4 TEAEs
Abbreviations: CTCAE, Common Terminology Criteria for Adverse Events; TEAE, treatment-emergent adverse event
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.