Breast Cancer
Conditions
Keywords
Breast Cancer, Gadobutrol-enhanced MRI, Mammography, Diagnostic Imaging
Brief summary
The purpose of this study is to look at the efficacy (how does it work) and safety of gadobutrol when used for obtaining MR images of both breasts.Women with a recent diagnosis of breast cancer by mammogram (X-ray examination of the breasts) may benefit from MRI of the breasts as MRI may detect additional breast cancers
Interventions
A single bolus injection of gadobutrol 1.0 M; 0.1 mmol/kg body weight
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Recent histologically proven diagnosis of breast cancer after having obtained X-Ray Mammography (XRM) of both breasts (according to American College of Radiology \[ACR\] and performed no longer than 6 weeks prior to enrollment into the study) and has been referred for a contrast-enhanced Magnetic Resonance Mammography (MRM) prior to surgery of the breast. * if female, a digital XRM is required if any of the following criteria is met: * a. patient is younger than 50 years; * b. patient has heterogeneously or extremely dense breasts; * c. is not post-menopausal (post-menopause defined as at least 12 months prior to inclusion without menstruation). * if female of childbearing potential, MRM should be performed on the 7-14th day of the menstrual cycle. * has an estimated glomerular filtration rate (eGFR) value \>/= 60 mL/min/1.73m\^2 derived from a serum creatinine result within 2 weeks prior to study enrollment.
Exclusion criteria
* is a female patient who is pregnant or lactating * has any contraindication to the MRM examination (e.g. metal implants, phobia) or the use of gadolinium-containing contrast agents. * has received any contrast agent within 24 hours prior to the study MRM, or is scheduled to receive any contrast agent within 24 hours after the study MRM. * has severe cardiovascular disease (e.g., known long QT syndrome, acute myocardial infarction \[\< 14 days\], unstable angina, congestive heart failure New York Heart Association class IV) or acute stroke (\< 48 hours)). * has acute renal insufficiency of any severity due to hepato-renal syndrome or in the peri-operative liver transplantation period or who has acute or chronic moderate or severe renal insufficiency (glomerular filtration rate \< 60 mL/min/1.73m\^2). * has received chemotherapy or hormonal therapy for breast cancer within 6 months. * has received hormone replacement therapy within 4 weeks prior to study drug administration. * is scheduled or likely to require a surgery and/or biopsy in the time period up to 24 hours following study drug application * has prior excisional biopsy or breast surgery less than 6 months before enrollment and between XRM and study MRM
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Immediately before injection and after injection | For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the clinical investigators and the 3 blinded readers using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. The difference was calculated as CMRM value minus UMRM value. For ease of expression, the following abbreviations will be used: Magnetic Resonance Mammography (MRM), Unenhanced MRM (UMRM), combined unenhanced and contrast (gadobutrol)-enhanced MRM (CMRM), X-ray mammography (XRM). |
| Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Immediately before injection and after injection | For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the clinical investigators and the 3 blinded readers using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. |
| Breast Level Specificity of CMRM for Non-malignant Breasts by Reader | Immediately before injection and after injection | A non-malignant breast was defined as false positive (FP), when the reader assessed at least one breast region as malignant. When all breast regions were assessed as non-malignant, the breast was defined as true negative (TN). Breast level specificity was first defined in participant as number of TN-breasts in participant divided by number of non-malignant breasts in participant. Subsequently the specificity percentage was calculated based on the mean of the specificities across all participants who contributed with at least one non-malignant breast. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Breast Level Specificity of CMRM Based on Malignant Breasts | Immediately before injection and after injection | A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). |
| Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level | Immediately before injection and after injection | The investigator and the blinded readers each recorded his/her confidence in diagnosis for each breast region based on a 4-point scale (1 = not confident, 2 = somewhat confident, 3 = confident, and 4 = very confident). For each participant, the mean of the confidence responses for the diagnosed breast regions was calculated, and rounded to the nearest 0.5. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively. |
| Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Immediately before injection and after injection | Index cancer was defined as the cancer confirmed by histology prior to inclusion which made the participants eligible for the study. The difference in percentage of participants was calculated as CMRM value minus UMRM value, CMRM value minus XRM value, CMRM value minus CMRM+XRM value respectively. |
| Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Immediately before injection and after injection | Additional cancer was defined as cancer which was present according to SoT, but which was not defined as index cancer, i.e. was not known when the participant was enrolled into the study. The difference in percentage of participants was calculated as CMRM value minus UMRM value, CMRM value minus XRM value, CMRM value minus CMRM+XRM value respectively. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Immediately before injection and after injection | A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively. |
| Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Immediately before injection and after injection | A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively. |
| Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Immediately before injection and after injection | A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively. |
| Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Immediately before injection and after injection | For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively. |
| Accuracy Difference of Presence of Bilateral Malignant Disease Verified by SoT by Clinical Investigator, Participant Level | Immediately before injection and after injection | The disease state bilateral malignant disease was derived from the assessment of the different regions for each breast (right and left) for investigators for each imaging modality (UMRM, CMRM, XRM, UMRM+XRM, and CMRM+XRM) based on the following rule: If the participant had at least one breast with no malignant region , the assessment of bilateral malignant disease was categorized as No. If the participant had at least one malignant lesion in both breasts, the assessment of bilateral malignant disease was categorized as Yes. The proportion of correct matches of each different image set to the SoT for the existence of bilateral malignant disease were derived. The analysis was based on the difference in accuracy for the evaluation of bilateral malignant disease for the following image comparisons on a participant level. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively. |
| Blinded Readers: Inter-reader Agreement on Sensitivity Based on Assessment for UMRM vs CMRM - Breast Region Level | Immediately before injection and after injection | Inter-reader agreement was assessed by considering each breast region to have 2 possibilities (malignant disease / no malignant disease) for an assessment by the 2 image sets (UMRM and CMRM). Kappa value varies from 0 (no agreement) to 1 (perfect agreement). |
| Blinded Reader 1: Intra-reader Variability Based on Assessment for CMRM - Breast Level | Immediately before injection and after injection | Intra-reader variability was assessed using a kappa on the match to SoT for the different regions within each participant (match, no match SoT). For each of the 3 readers, intra-reader agreement was assessed by considering each breast region to have 2 possibilities for an assessment by CMRM: matched SoT or did not match SoT. Kappa value varies from 0 (no agreement) to 1 (perfect agreement). |
| Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Immediately before injection and after injection | A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). |
| Blinded Reader 3: Intra-reader Variability Based on Assessment for CMRM - Breast Level | Immediately before injection and after injection | Intra-reader variability was assessed using a kappa on the match to SoT for the different regions within each participant (match, no match SoT). For each of the 3 readers, intra-reader agreement was assessed by considering each breast region to have 2 possibilities for an assessment by CMRM: matched SoT or did not match SoT. Kappa value varies from 0 (no agreement) to 1 (perfect agreement). |
| Categorical Accuracy Difference of Extent of Malignant Disease Verified by SoT by Majority Reader, Breast Region Level | Immediately before injection and after injection | — |
| Categorical Accuracy Difference of Extent of Malignant Disease Verified by Histopathology by Majority Reader, Breast Region Level | Immediately before injection and after injection | — |
| Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Systolic and Diastolic Blood Pressure | Baseline, 24 hours post injection | Systolic and diastolic blood pressure were measured in a supine position. Blood pressure was not to be measured on the arm used for the injection. |
| Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Heart Rate | Baseline, Follow-up visit (24 hours post injection) | Heart rate was measured in a supine position. |
| Number of Participants With at Least One Laboratory Parameter Change From Low or Normal at Baseline to Abnormally High at Follow-up 24 Hours Post Injection | Baseline, Follow-up visit (24 hours post injection) | Number of participants with at least one occurrence of changing from low or normal at baseline to high at follow-up. |
| Blinded Reader 2: Intra-reader Variability Based on Assessment for CMRM - Breast Level | Immediately before injection and after injection | Intra-reader variability was assessed using a kappa on the match to SoT for the different regions within each participant (match, no match SoT). For each of the 3 readers, intra-reader agreement was assessed by considering each breast region to have 2 possibilities for an assessment by CMRM: matched SoT or did not match SoT. Kappa value varies from 0 (no agreement) to 1 (perfect agreement). |
| Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Immediately before injection and after injection | For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. |
| Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Immediately before injection and after injection | A non-malignant breast was defined as false positive (FP), when the reader assessed at least one breast region as malignant. When all breast regions were assessed as non-malignant, the breast was defined as true negative (TN). Breast level specificity was first defined in participant as number of TN-breasts in participant divided by number of non-malignant breasts in participant. Subsequently the specificity percentage was calculated based on the mean of the specificities across all participants who contributed with at least one non-malignant breast. |
| Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Immediately before injection and after injection | A non-malignant breast was defined as FP when the reader assessed at least one breast region as malignant. A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as (N-FP)/N, where N was total number of breasts. |
| Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Immediately before injection and after injection | For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. Regions with malignant disease verified by SoT comprise unifocal and multifocal regions. Difference in sensitivity is calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively. |
| Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Immediately before injection and after injection | For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. The difference in sensitivity is calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively. |
| Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Immediately before injection and after injection | For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. The difference in sensitivity is calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively. |
Countries
Argentina, Canada, Germany, India, Netherlands, Poland, Spain, Taiwan, United States
Participant flow
Recruitment details
Recruitment period: 16 May 2010 - 27 Sep 2011
Participants by arm
| Arm | Count |
|---|---|
| Gadobutrol (Gadavist, BAY86-4875) Participants first received an unenhanced MRM, followed by a gadobutrol-enhanced MRM. Gadobutrol was administered at the standard dose of 0.1 mmol/kg bw \[0.1 ml/kg bw\] as an i.v. injection at a rate of 2 ml/sec. UMRM and CMRM image sets were evaluated in a randomized fashion. After the evaluation of the UMRM or CMRM the respective XRM was added and evaluated together with the UMRM images. | 439 |
| Total | 439 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study drug never administered | 21 |
| Overall Study | Study prematurely discontinued | 2 |
Baseline characteristics
| Characteristic | Gadobutrol (Gadavist, BAY86-4875) |
|---|---|
| Age, Continuous | 57.1 years STANDARD_DEVIATION 10.7 |
| Country Argentina | 19 participants |
| Country Canada | 33 participants |
| Country Germany | 91 participants |
| Country India | 63 participants |
| Country Poland | 70 participants |
| Country Spain | 66 participants |
| Country Taiwan | 36 participants |
| Country United States | 61 participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 1 participants |
| Race/Ethnicity, Customized Asian | 104 participants |
| Race/Ethnicity, Customized Black | 17 participants |
| Race/Ethnicity, Customized Missing | 7 participants |
| Race/Ethnicity, Customized White | 310 participants |
| Sex: Female, Male Female | 438 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 439 |
| serious Total, serious adverse events | 0 / 439 |
Outcome results
Primary
Breast Level Specificity of CMRM for Non-malignant Breasts by Reader
A non-malignant breast was defined as false positive (FP), when the reader assessed at least one breast region as malignant. When all breast regions were assessed as non-malignant, the breast was defined as true negative (TN). Breast level specificity was first defined in participant as number of TN-breasts in participant divided by number of non-malignant breasts in participant. Subsequently the specificity percentage was calculated based on the mean of the specificities across all participants who contributed with at least one non-malignant breast.
Time frame: Immediately before injection and after injection
Population: The analyses were based on 367 participants in FAS; evaluable for specificity were breasts without malignant disease as verified by Standard of Truth (SoT) for which a CMRM assessment was available.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Breast Level Specificity of CMRM for Non-malignant Breasts by Reader | Reader 1 | 91.8 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity of CMRM for Non-malignant Breasts by Reader | Reader 2 | 83.9 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity of CMRM for Non-malignant Breasts by Reader | Reader 3 | 82.8 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity of CMRM for Non-malignant Breasts by Reader | Investigator | 95.4 specificity (%) |
Primary
Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the clinical investigators and the 3 blinded readers using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. The difference was calculated as CMRM value minus UMRM value. For ease of expression, the following abbreviations will be used: Magnetic Resonance Mammography (MRM), Unenhanced MRM (UMRM), combined unenhanced and contrast (gadobutrol)-enhanced MRM (CMRM), X-ray mammography (XRM).
Time frame: Immediately before injection and after injection
Population: The analyses were based on 390 participants in the Full Analysis Set (FAS) who had regions with malignant disease verified by Standard of Truth (SoT).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Reader 3 | 30.4 difference in sensitivity (%) |
| CMRM Versus UMRM | Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Reader 1 | 15.2 difference in sensitivity (%) |
| CMRM Versus UMRM | Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Reader 2 | 31.9 difference in sensitivity (%) |
| CMRM Versus UMRM | Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Investigator | 15.9 difference in sensitivity (%) |
Primary
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the clinical investigators and the 3 blinded readers using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants.
Time frame: Immediately before injection and after injection
Population: The analyses were based on 390 participants in the Full Analysis Set (FAS) who had regions with malignant disease verified by Standard of Truth (SoT).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Reader 1 | 88.6 sensitivity (%) |
| CMRM Versus UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Reader 2 | 89.0 sensitivity (%) |
| CMRM Versus UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Reader 3 | 85.5 sensitivity (%) |
| CMRM Versus UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Investigator | 95.5 sensitivity (%) |
| UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Investigator | 79.5 sensitivity (%) |
| UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Reader 1 | 73.3 sensitivity (%) |
| UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Reader 3 | 55.1 sensitivity (%) |
| UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader | Reader 2 | 57.0 sensitivity (%) |
Secondary
Breast Level Specificity of CMRM Based on Malignant Breasts
A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP).
Time frame: Immediately before injection and after injection
Population: The analyses were based on 390 participants in FAS; evaluable for specificity were breasts with malignant disease verified by SoT for which an assessment by the imaging modality was available.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Breast Level Specificity of CMRM Based on Malignant Breasts | Reader 1 | 54.9 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity of CMRM Based on Malignant Breasts | Reader 2 | 47.2 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity of CMRM Based on Malignant Breasts | Reader 3 | 55.5 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity of CMRM Based on Malignant Breasts | Investigator | 93.8 specificity (%) |
Secondary
Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level
The investigator and the blinded readers each recorded his/her confidence in diagnosis for each breast region based on a 4-point scale (1 = not confident, 2 = somewhat confident, 3 = confident, and 4 = very confident). For each participant, the mean of the confidence responses for the diagnosed breast regions was calculated, and rounded to the nearest 0.5. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level | Reader 2 | 0.95 difference of scores on a scale |
| CMRM Versus UMRM | Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level | Reader 1 | 0.97 difference of scores on a scale |
| CMRM Versus UMRM | Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level | Reader 3 | 1.73 difference of scores on a scale |
| UMRM | Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level | Reader 2 | 0.74 difference of scores on a scale |
| UMRM | Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level | Reader 1 | 1.25 difference of scores on a scale |
| UMRM | Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level | Reader 3 | 1.64 difference of scores on a scale |
| CMRM vs CMRM+XRM | Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level | Reader 1 | -0.23 difference of scores on a scale |
| CMRM vs CMRM+XRM | Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level | Reader 3 | 0.67 difference of scores on a scale |
| CMRM vs CMRM+XRM | Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level | Reader 2 | 0.04 difference of scores on a scale |
Secondary
Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Additional cancer was defined as cancer which was present according to SoT, but which was not defined as index cancer, i.e. was not known when the participant was enrolled into the study. The difference in percentage of participants was calculated as CMRM value minus UMRM value, CMRM value minus XRM value, CMRM value minus CMRM+XRM value respectively.
Time frame: Immediately before injection and after injection
Population: The evaluation was based on the 84 participants in the FAS who had at least one additional cancer region according to SoT.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CMRM Versus UMRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 1 | 23.8 difference in percentage of participants |
| CMRM Versus UMRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 2 | 44.0 difference in percentage of participants |
| CMRM Versus UMRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 3 | 34.5 difference in percentage of participants |
| CMRM Versus UMRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Investigator | 35.7 difference in percentage of participants |
| UMRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Investigator | 40.5 difference in percentage of participants |
| UMRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 1 | 42.9 difference in percentage of participants |
| UMRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 3 | 26.2 difference in percentage of participants |
| UMRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 2 | 48.8 difference in percentage of participants |
| CMRM vs CMRM+XRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Investigator | -1.2 difference in percentage of participants |
| CMRM vs CMRM+XRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 2 | 0.0 difference in percentage of participants |
| CMRM vs CMRM+XRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 3 | -2.4 difference in percentage of participants |
| CMRM vs CMRM+XRM | Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 1 | 0.0 difference in percentage of participants |
Secondary
Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Index cancer was defined as the cancer confirmed by histology prior to inclusion which made the participants eligible for the study. The difference in percentage of participants was calculated as CMRM value minus UMRM value, CMRM value minus XRM value, CMRM value minus CMRM+XRM value respectively.
Time frame: Immediately before injection and after injection
Population: The analyses were based on 388 participants in FAS; index cancer was defined as the cancer confirmed by histology prior to inclusion which made the participant eligible for the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CMRM Versus UMRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 2 | 30.2 difference in percentage of participants |
| CMRM Versus UMRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 1 | 15.5 difference in percentage of participants |
| CMRM Versus UMRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Investigator | 14.2 difference in percentage of participants |
| CMRM Versus UMRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 3 | 30.9 difference in percentage of participants |
| UMRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 1 | 19.8 difference in percentage of participants |
| UMRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Investigator | 2.3 difference in percentage of participants |
| UMRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 3 | 12.9 difference in percentage of participants |
| UMRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 2 | 13.9 difference in percentage of participants |
| CMRM vs CMRM+XRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Investigator | -0.5 difference in percentage of participants |
| CMRM vs CMRM+XRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 3 | -2.6 difference in percentage of participants |
| CMRM vs CMRM+XRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 2 | -1.3 difference in percentage of participants |
| CMRM vs CMRM+XRM | Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM | Reader 1 | -1.0 difference in percentage of participants |
Other Pre-specified
Accuracy Difference of Presence of Bilateral Malignant Disease Verified by SoT by Clinical Investigator, Participant Level
The disease state bilateral malignant disease was derived from the assessment of the different regions for each breast (right and left) for investigators for each imaging modality (UMRM, CMRM, XRM, UMRM+XRM, and CMRM+XRM) based on the following rule: If the participant had at least one breast with no malignant region , the assessment of bilateral malignant disease was categorized as No. If the participant had at least one malignant lesion in both breasts, the assessment of bilateral malignant disease was categorized as Yes. The proportion of correct matches of each different image set to the SoT for the existence of bilateral malignant disease were derived. The analysis was based on the difference in accuracy for the evaluation of bilateral malignant disease for the following image comparisons on a participant level. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Time frame: Immediately before injection and after injection
Population: The analyses were based on 380 participants in FAS; evaluable subjects with at least one region verified by SoT in each breast with available CMRM, UMRM, CMRM+XRM, UMRM+XRM and XRM assessment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CMRM Versus UMRM | Accuracy Difference of Presence of Bilateral Malignant Disease Verified by SoT by Clinical Investigator, Participant Level | 0.5 difference in accuracy (%) |
| UMRM | Accuracy Difference of Presence of Bilateral Malignant Disease Verified by SoT by Clinical Investigator, Participant Level | -0.3 difference in accuracy (%) |
| CMRM vs CMRM+XRM | Accuracy Difference of Presence of Bilateral Malignant Disease Verified by SoT by Clinical Investigator, Participant Level | -0.8 difference in accuracy (%) |
Other Pre-specified
Blinded Reader 1: Intra-reader Variability Based on Assessment for CMRM - Breast Level
Intra-reader variability was assessed using a kappa on the match to SoT for the different regions within each participant (match, no match SoT). For each of the 3 readers, intra-reader agreement was assessed by considering each breast region to have 2 possibilities for an assessment by CMRM: matched SoT or did not match SoT. Kappa value varies from 0 (no agreement) to 1 (perfect agreement).
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CMRM Versus UMRM | Blinded Reader 1: Intra-reader Variability Based on Assessment for CMRM - Breast Level | 0.25 Kappa |
Other Pre-specified
Blinded Reader 2: Intra-reader Variability Based on Assessment for CMRM - Breast Level
Intra-reader variability was assessed using a kappa on the match to SoT for the different regions within each participant (match, no match SoT). For each of the 3 readers, intra-reader agreement was assessed by considering each breast region to have 2 possibilities for an assessment by CMRM: matched SoT or did not match SoT. Kappa value varies from 0 (no agreement) to 1 (perfect agreement).
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CMRM Versus UMRM | Blinded Reader 2: Intra-reader Variability Based on Assessment for CMRM - Breast Level | 0.23 Kappa |
Other Pre-specified
Blinded Reader 3: Intra-reader Variability Based on Assessment for CMRM - Breast Level
Intra-reader variability was assessed using a kappa on the match to SoT for the different regions within each participant (match, no match SoT). For each of the 3 readers, intra-reader agreement was assessed by considering each breast region to have 2 possibilities for an assessment by CMRM: matched SoT or did not match SoT. Kappa value varies from 0 (no agreement) to 1 (perfect agreement).
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CMRM Versus UMRM | Blinded Reader 3: Intra-reader Variability Based on Assessment for CMRM - Breast Level | 0.21 Kappa |
Other Pre-specified
Blinded Readers: Inter-reader Agreement on Sensitivity Based on Assessment for UMRM vs CMRM - Breast Region Level
Inter-reader agreement was assessed by considering each breast region to have 2 possibilities (malignant disease / no malignant disease) for an assessment by the 2 image sets (UMRM and CMRM). Kappa value varies from 0 (no agreement) to 1 (perfect agreement).
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CMRM Versus UMRM | Blinded Readers: Inter-reader Agreement on Sensitivity Based on Assessment for UMRM vs CMRM - Breast Region Level | 0.47 Kappa |
Other Pre-specified
Breast Level Specificity for All Breasts by Imaging Modality and by Reader
A non-malignant breast was defined as FP when the reader assessed at least one breast region as malignant. A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as (N-FP)/N, where N was total number of breasts.
Time frame: Immediately before injection and after injection
Population: The analyses were based on 395 participants in FAS; evaluable for specificity were breasts with or without malignant disease verified by SoT with available assessments by the imaging modality.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 1 | 83.0 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Investigator | 96.6 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 3 | 86.5 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 2 | 86.1 specificity (%) |
| UMRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Investigator | 94.1 specificity (%) |
| UMRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 1 | 73.0 specificity (%) |
| UMRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 2 | 64.9 specificity (%) |
| UMRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 3 | 68.6 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 1 | 89.7 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 3 | 77.6 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 2 | 83.0 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Investigator | 97.1 specificity (%) |
| UMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 3 | 75.9 specificity (%) |
| UMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 2 | 77.8 specificity (%) |
| UMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 1 | 81.3 specificity (%) |
| UMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Investigator | 96.2 specificity (%) |
| CMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 3 | 68.1 specificity (%) |
| CMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 1 | 72.0 specificity (%) |
| CMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Reader 2 | 64.3 specificity (%) |
| CMRM+XRM | Breast Level Specificity for All Breasts by Imaging Modality and by Reader | Investigator | 94.0 specificity (%) |
Other Pre-specified
Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP).
Time frame: Immediately before injection and after injection
Population: The analyses were based on 390 participants; evaluable for specificity were breasts with malignant disease verified by SoT for which an assessment by the imaging modality was available.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 2 | 76.2 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 3 | 77.6 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Investigator | 96.2 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 1 | 71.9 specificity (%) |
| UMRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Investigator | 97.7 specificity (%) |
| UMRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 1 | 86.8 specificity (%) |
| UMRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 2 | 75.8 specificity (%) |
| UMRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 3 | 69.4 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Investigator | 93.8 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 1 | 52.7 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 2 | 46.5 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 3 | 54.5 specificity (%) |
| UMRM+XRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Investigator | 96.0 specificity (%) |
| UMRM+XRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 1 | 69.1 specificity (%) |
| UMRM+XRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 3 | 66.9 specificity (%) |
| UMRM+XRM | Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 2 | 65.4 specificity (%) |
Other Pre-specified
Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
A non-malignant breast was defined as false positive (FP), when the reader assessed at least one breast region as malignant. When all breast regions were assessed as non-malignant, the breast was defined as true negative (TN). Breast level specificity was first defined in participant as number of TN-breasts in participant divided by number of non-malignant breasts in participant. Subsequently the specificity percentage was calculated based on the mean of the specificities across all participants who contributed with at least one non-malignant breast.
Time frame: Immediately before injection and after injection
Population: The analyses were based on 367 participants; evaluable for specificity were breasts with no malignant disease verified by SoT for which an assessment of the imaging modality was available.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 3 | 95.9 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Investigator | 98.1 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 1 | 94.4 specificity (%) |
| CMRM Versus UMRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 2 | 96.6 specificity (%) |
| UMRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 2 | 90.3 specificity (%) |
| UMRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 1 | 92.6 specificity (%) |
| UMRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Investigator | 97.8 specificity (%) |
| UMRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 3 | 86.1 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 2 | 83.1 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Investigator | 95.1 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 1 | 92.2 specificity (%) |
| CMRM vs CMRM+XRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 3 | 83.0 specificity (%) |
| UMRM+XRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 2 | 91.0 specificity (%) |
| UMRM+XRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Investigator | 97.5 specificity (%) |
| UMRM+XRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 3 | 85.1 specificity (%) |
| UMRM+XRM | Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader | Reader 1 | 94.3 specificity (%) |
Other Pre-specified
Categorical Accuracy Difference of Extent of Malignant Disease Verified by Histopathology by Majority Reader, Breast Region Level
Time frame: Immediately before injection and after injection
Population: The Statistical Analysis Plan (SAP) amendment re-defined study objectives and replaced protocol-defined parameters such as categorical accuracy prior to database closure and breaking the blind. The SAP amendment is based upon review of results of an identical clinical study within the GEMMA program and also includes advice from the FDA.
Other Pre-specified
Categorical Accuracy Difference of Extent of Malignant Disease Verified by SoT by Majority Reader, Breast Region Level
Time frame: Immediately before injection and after injection
Population: The Statistical Analysis Plan (SAP) amendment re-defined study objectives and replaced protocol-defined parameters such as categorical accuracy prior to database closure and breaking the blind. The SAP amendment is based upon review of results of an identical clinical study within the GEMMA program and also includes advice from the FDA.
Other Pre-specified
Number of Participants With at Least One Laboratory Parameter Change From Low or Normal at Baseline to Abnormally High at Follow-up 24 Hours Post Injection
Number of participants with at least one occurrence of changing from low or normal at baseline to high at follow-up.
Time frame: Baseline, Follow-up visit (24 hours post injection)
Population: Safety Analysis Set (SAF): The analysis of safety data was performed using all available data from all participants who administered any amount of gadobutrol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CMRM Versus UMRM | Number of Participants With at Least One Laboratory Parameter Change From Low or Normal at Baseline to Abnormally High at Follow-up 24 Hours Post Injection | Urinalysis | 144 Participants |
| CMRM Versus UMRM | Number of Participants With at Least One Laboratory Parameter Change From Low or Normal at Baseline to Abnormally High at Follow-up 24 Hours Post Injection | Hematology | 41 Participants |
| CMRM Versus UMRM | Number of Participants With at Least One Laboratory Parameter Change From Low or Normal at Baseline to Abnormally High at Follow-up 24 Hours Post Injection | Clinical chemistry | 107 Participants |
Other Pre-specified
Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. Regions with malignant disease verified by SoT comprise unifocal and multifocal regions. Difference in sensitivity is calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | 17.5 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | 34.9 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | 32.1 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | 19.0 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | 6.7 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | 10.0 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | 9.5 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | 12.5 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | 24.3 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | 21.3 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | 10.5 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | 16.5 difference in sensitivity (%) |
Other Pre-specified
Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. The difference in sensitivity is calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | 25.4 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | 31.7 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | 51.7 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | 46.7 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | 21.7 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | 35.0 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | 21.7 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | 40.0 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | 46.7 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | 36.7 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | 65.0 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | 11.7 difference in sensitivity (%) |
Other Pre-specified
Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. The difference in sensitivity is calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -5.8 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | 4.6 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | 19.5 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | 12.0 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -12.3 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | -1.9 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -12.6 difference in sensitivity (%) |
| UMRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | 0.2 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | 6.9 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -12.0 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | 2.3 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -10.2 difference in sensitivity (%) |
Other Pre-specified
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants.
Time frame: Immediately before injection and after injection
Population: The analyses were performed for a total number of 390 participants who had regions with malignant disease verified by SoT with available assessment by the imaging modality.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Reader 1 | 69.6 sensitivity (%) |
| CMRM Versus UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Reader 2 | 72.9 sensitivity (%) |
| CMRM Versus UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Reader 3 | 73.2 sensitivity (%) |
| CMRM Versus UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Investigator | 89.1 sensitivity (%) |
| UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Investigator | 96.0 sensitivity (%) |
| UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Reader 1 | 89.6 sensitivity (%) |
| UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Reader 3 | 88.0 sensitivity (%) |
| UMRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Reader 2 | 90.3 sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Investigator | 92.1 sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Reader 2 | 80.9 sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Reader 3 | 80.1 sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader | Reader 1 | 82.5 sensitivity (%) |
Other Pre-specified
Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Reader 1 | 47.7 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Reader 3 | 47.7 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Reader 2 | 56.8 difference in sensitivity (%) |
| CMRM Versus UMRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Investigator | 34.1 difference in sensitivity (%) |
| UMRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Reader 1 | 38.6 difference in sensitivity (%) |
| UMRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Investigator | 31.8 difference in sensitivity (%) |
| UMRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Reader 3 | 31.8 difference in sensitivity (%) |
| UMRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Reader 2 | 40.9 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Investigator | 52.3 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Reader 3 | 43.2 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Reader 2 | 61.4 difference in sensitivity (%) |
| CMRM vs CMRM+XRM | Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level | Reader 1 | 75.0 difference in sensitivity (%) |
Other Pre-specified
Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -4.1 difference in specificity (%) |
| CMRM Versus UMRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -8.4 difference in specificity (%) |
| CMRM Versus UMRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | -6.1 difference in specificity (%) |
| CMRM Versus UMRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | -1.0 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | -0.9 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -3.9 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | -2.0 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -5.7 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | -1.3 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -7.5 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | -3.2 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -6.7 difference in specificity (%) |
Other Pre-specified
Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -4.4 difference in specificity (%) |
| CMRM Versus UMRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -6.5 difference in specificity (%) |
| CMRM Versus UMRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | -2.3 difference in specificity (%) |
| CMRM Versus UMRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | 1.1 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | -0.7 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -5.3 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | -2.0 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -6.7 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | -0.7 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -8.2 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | -1.9 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -7.5 difference in specificity (%) |
Other Pre-specified
Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Time frame: Immediately before injection and after injection
Population: All participants in the FAS with assessments for this outcome measure
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CMRM Versus UMRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -3.2 difference in specificity (%) |
| CMRM Versus UMRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -7.3 difference in specificity (%) |
| CMRM Versus UMRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | -5.4 difference in specificity (%) |
| CMRM Versus UMRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | -0.4 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | -0.4 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -3.1 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | -1.6 difference in specificity (%) |
| UMRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -5.0 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Investigator | -0.5 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 2 | -6.6 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 3 | -3.1 difference in specificity (%) |
| CMRM vs CMRM+XRM | Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level | Reader 1 | -5.6 difference in specificity (%) |
Other Pre-specified
Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Heart Rate
Heart rate was measured in a supine position.
Time frame: Baseline, Follow-up visit (24 hours post injection)
Population: Safety Analysis Set (SAF): The analysis of safety data was performed using all available data from all participants who administered any amount of gadobutrol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CMRM Versus UMRM | Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Heart Rate | -1.7 beats/min | Standard Deviation 10.1 |
Other Pre-specified
Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Systolic and Diastolic Blood Pressure
Systolic and diastolic blood pressure were measured in a supine position. Blood pressure was not to be measured on the arm used for the injection.
Time frame: Baseline, 24 hours post injection
Population: Safety Analysis Set (SAF): The analysis of safety data was performed using all available data from all participants who administered any amount of gadobutrol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CMRM Versus UMRM | Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Systolic and Diastolic Blood Pressure | Systolic blood pressure | -2.7 mmHg | Standard Deviation 15.2 |
| CMRM Versus UMRM | Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Systolic and Diastolic Blood Pressure | Diastolic blood pressure | -2.3 mmHg | Standard Deviation 9.7 |