Elinzanetant reduces the frequency of vasomotor symptoms by approximately 2–3 episodes per day compared with placebo, the magnitude exceeds the minimally important difference (MID). It also appears to decrease symptom severity by about 0.3–0.4 points, a magnitude that meets or slightly exceeds the MID.
We downgraded the level of the evidence due to study limitations (moderate dropout rate), imprecision, indirectness, and possible publication bias.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| «Pinkerton JV, Simon JA, Joffe H, et al. Elinzaneta...»1 | 2xRCT (OASIS 1 and OASIS 2) | Postmenopausal participants (mean age 54.6 years) experiencing moderate to severe vasomotor symptoms (OASIS 1: 77 sites in the US, Europe, and, and OASIS 2: 77 sites in the US, Canada, and Europe). | Elinzanetant 120 mg per orally once a day vs placebo | Primary outcome: mean change in frequency and severity of moderate to severe vasomotor symptoms measured
by the electronic hot flash daily diary Secondary outcome: changes in sleep disturbance and the effect on menopause-related quality of life. |
moderate |
| «Panay N, Joffe H, Maki PM, et al. Elinzanetant for...»2 | RCT | OASIS 3: Postmenopausal women (mean age, 54.6 years) who were seeking treatment for moderate to severe VMS (no requirement for a minimum number of VMS events per week), 83 sites in North America and Europe | Elinzanetant 120 mg per orally once a day vs placebo | Primary outcome: mean change in the frequency of daily moderate to severe VMS. Secondary outcome: changes in sleep disturbance and the effect on menopause-related quality of life. |
moderate |
| «Cardoso F, Parke S, Brennan DJ, et al. Elinzanetan...»3 | RCT | OASIS 4: Women 18 to 70 years of age with moderate to-severe vasomotor symptoms associated with endocrine therapy for HR-positive breast cancer or its prevention |
Elinzanetant 120 mg per orally once a day vs placebo | Primary outcomes: change in the mean daily frequency of moderate-to-severe vasomotor symptoms | |
| RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis, VMS=vasomotor symptoms | |||||
| Reference | Comments |
|---|---|
| «Pinkerton JV, Simon JA, Joffe H, et al. Elinzaneta...»1 | Inclusion citeria: OASIS 1 and 2 included naturally or surgically (bilateral oophorectomy with or without
hysterectomy) postmenopausal participants, aged 40 to 65 years and experiencing 50
or more moderate to severe VMS over 7 days during screening. Exclusion criteria: abnormal liver parameters (including alanine aminotransferase or asp artate aminotransferase
>2 × upper limit of normal), disordered proliferative endometrium, endometrial hyperplasia
or polyps, and current or history of malignancy within the last 5 years (except basal
and squamous cell skin tumors). We did not detect factors in original trials that can reduce the quality of evidence such as sequence (randomisation), concealment, blinding (participants/personnel), incomplete data, selective outcome reporting, other limitations for RCTs but the dropout rate was moderate (~15%). |
| «Panay N, Joffe H, Maki PM, et al. Elinzanetant for...»2 | Inclusion citeria: naturally or surgically postmenopausal women aged 40 to 65 years who were seeking
treatment for moderate to severe VMS.23 Surgical menopause was defined as bilateral
oophorectomy with or without hysterectomy at least6weeks before signing of informed
consent. There was no requirement for a minimum number ofV MS events per week. Exclusion criteria: abnormal liver parameters; disordered proliferative endometrium; endometrial polyp,
hyperplasia, or malignant neoplasm; and current or history of cancer within the last
5 years (except basal and squamous cell skin tumors). We did not detect factors in these two trials that can reduce the quality of evidence such as sequence (randomisation), concealment, blinding (participants/personnel), incomplete data, selective outcome reporting, and other limitations for RCTs but the dropout rate was moderate (~15%). |
| «Cardoso F, Parke S, Brennan DJ, et al. Elinzanetan...»3 | Inclusion criteria: women 18 to 70 years of age who were receiving endocrine therapy (tamoxifen or aromatase inhibitors with or without GnRH analogues) for HR-positive breast cancer or its prevention among those at high risk for breast cancer and had at least 35 moderate-to-severe vasomotor symptoms per week that were associated with endocrine therapy. The trial was designed to enroll at least 40% of participants receiving tamoxifen and at least 40% receiving aromatase inhibitors.Exclusion criteria: an initial diagnosis of metastatic HR-positive breast cancer or a recurrence of HR-positive breast cancer while receiving endocrine therapy; surgical or nonsurgical treatment for breast cancer (with the exception of tamoxifen, aromatase inhibitors, and GnRH analogues) within 3 months before signing informed consent; surgery, chemotherapy, radiotherapy, or immunotherapy that was scheduled to take place during the trial; or concomitant administration of certain medications |
Results
| Reference | Number of studies and number of patients: I/C | Follow-up time | Change in VMS frequency (SD/95% CI), I | Change in VMS frequency (SD1. 95% CI(2., 3.)) | Least square mean change (95% CI) |
|---|---|---|---|---|---|
| «Pinkerton JV, Simon JA, Joffe H, et al. Elinzaneta...»1 | 2 RCTs; OASIS 1: 199/197; OASIS 2: 200/200 | 12 weeks | OASIS 1: −8.7 (6.7) OASIS 2: −10.0 (10.3) |
OASIS 1: −5.5 (10.2), OASIS 2: −7.2 (8.5) |
OASIS 1: −3.2 (−4.8 to −1.6) OASIS 2: −3.2 (−4.6 to −1.9) |
| «Panay N, Joffe H, Maki PM, et al. Elinzanetant for...»2 | OASIS 3: 313/315 | 12 weeks | OASIS 3: −5.4 (−6.3 to −4.5) | OASIS 3: −3.5 (−4.1 to −2.9) | OASIS 3: −1.6 (−2.0 to −1.1) |
| «Cardoso F, Parke S, Brennan DJ, et al. Elinzanetan...»3 | OASIS 4: 316/158 | 12 weeks | −7.8 ( −8.5 to −7.1) | −4.2 ( −5.2 to −3.2) | −3.4 (−4.2 to −2.5) |
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations, indirectness, and possible publication bias. I= intervention; C=comparison; CI=confidence interval, VMS=vasomotor symptoms |
|||||
| Reference | Number of studies and number of patients: I/C | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Least square mean change (95% CI) |
|---|---|---|---|---|---|
| «Pinkerton JV, Simon JA, Joffe H, et al. Elinzaneta...»1 | 2 RCTs; OASIS 1: 199/197; OASIS 2: 200/200 | 12 weeks | - | - | OASIS 1: −0.4 (95% CI −0.5 to −0.3); OASIS 2: −0.3 (95% CI−0.4 to −0.1) |
| «Panay N, Joffe H, Maki PM, et al. Elinzanetant for...»2 | OASIS 3: 313/315 | 12 weeks | - | - | - |
| «Cardoso F, Parke S, Brennan DJ, et al. Elinzanetan...»3 | OASIS 4: 316/158 | 12 weeks | - | - | - |
| Level of evidence: moderate The quality of evidence is downgraded due to study limitations, imprecision and possible publication bias. I= intervention; C=comparison; CI=confidence interval |
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