Breast Cancer
Conditions
Keywords
Metastatic breast cancer, HER2 negative breast cancer, locally recurrent breast cancer
Brief summary
The objective of this study is to compare the progression-free survival (PFS) of the drug combination ramucirumab plus docetaxel to placebo plus docetaxel in previously untreated participants with human epidermal growth factor receptor 2 (HER2)-negative, unresectable, locally-recurrent or metastatic breast cancer.
Detailed description
Female participants at least 18 years of age with histologically or cytologically confirmed, human epidermal growth factor receptor 2 (HER2) negative breast adenocarcinoma that is metastatic or locally-recurrent and inoperable with curative intent will be randomized. Participants may not have received chemotherapy for metastatic or locally-recurrent, inoperable breast cancer. It is anticipated that 1113 participants will be randomized with 371 participants in the docetaxel plus placebo arm and 742 participants in the docetaxel plus ramucirumab (IMC-1121B) arm. There will be approximately 250 centers in North and South America, Europe, Asia, Middle East, Africa, Australia, and New Zealand. On Day 1 of each 21-day cycle, participants will receive docetaxel 75 mg/m² as a one-hour I.V. infusion followed by either ramucirumab (IMC-1121B) 10 mg/kg or placebo 10 mg/kg as a one-hour I.V. infusion. Each cycle is repeated every 21 days. Treatment will continue until there is evidence of progressive disease, unacceptable toxicity, or other withdrawal criteria are met. Participants who discontinue study treatment with either ramucirumab (IMC-1121B) or placebo may continue to receive docetaxel.
Interventions
BIOLOGICALramucirumab (IMC-1121B)
Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
DRUGdocetaxel
Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
OTHERPlacebo
Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is able to provide signed informed consent * Participant is female and ≥ 18 years of age or older if required by local laws or regulations * Participant has histologically or cytologically confirmed adenocarcinoma of the breast that is now metastatic or locally-recurrent and inoperable with curative intent. Every effort should be made to make paraffin-embedded tissue or slides from the diagnostic biopsy or surgical specimen available for confirmation of diagnosis * Participant has measurable and/or non-measurable disease * Participants' primary and/or metastatic tumor is human epidermal growth factor receptor 2 (HER2)-negative by fluorescence in-situ hybridization (FISH) or chromogenic in-situ hybridization (CISH) or 0, 1+ overexpression by immunohistochemistry (IHC) * Participant has not received prior chemotherapy for metastatic or locally-recurrent and inoperable breast cancer * Participant completed (neo) adjuvant taxane therapy at least 6 months prior to randomization * Participant completed (neo) adjuvant biologic therapy at least 6 weeks prior to randomization * Participant completed all prior radiotherapy with curative intent ≥ 3 weeks prior to randomization * Participant may have received prior hormonal therapy for breast cancer in the (neo) adjuvant and/or the metastatic setting ≥ 2 weeks prior to randomization * Participant's left ventricular ejection fraction is within normal institutional ranges * Participant has resolution to grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI-CTCAE v 3.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy which must have resolved to grade ≤ 2 * Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Participant is amenable to compliance with protocol schedules and testing * Participant has adequate hematological functions \[absolute neutrophil count (ANC) ≥ 1500 cells/microliter (mcL), hemoglobin ≥ 9 grams/deciliter (g/dL), and platelets ≥ 100,000 cells/mcL and ≤ 850,000 cells/mcL\] * Participant has adequate hepatic function \[bilirubin within normal limits (WNL), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times the upper limit of normal (ULN), or ≤ 5.0 times the ULN if the transaminase elevation is due to liver metastases, and alkaline phosphatase ≤ 5.0 times the ULN\] * Participant has serum creatinine ≤ 1.5 x ULN. If serum creatinine \> 1.5 x ULN the calculated creatinine clearance should be \> 40 milliliters/minute (mL/min) * Participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA); if urine protein ≥ 2+, a 24-hour urine collection must demonstrate \< 1000 milligrams (mg) of protein in 24 hours to allow participation in the study * Participant must have adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 1.5 X ULN if not receiving anticoagulation therapy. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin and if on warfarin must have a INR between 2 and 3 and have no active bleeding (defined as within 14 days of randomization) or pathological condition that carries a high risk of bleeding (such as, tumor involving major vessels or known varices) * Women of childbearing potential must implement adequate contraception in the opinion of the investigator * Participant has not received prior biologic therapy for metastatic or locally recurrent and inoperable breast cancer
Exclusion criteria
* Participant has a concurrent active malignancy other than breast adenocarcinoma, adequately treated non melanomatous skin cancer, or other non-invasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that she has been disease free for \> 3 years * Participant has a known sensitivity to docetaxel or other drugs formulated with polysorbate 80 * Participant has a known sensitivity to agents of similar biologic composition as ramucirumab or other agents that specifically target vascular endothelial growth factor (VEGF) * Participant has a history of chronic diarrheal disease within 6 months prior to randomization * Participant has received irradiation to a major bone marrow area as defined as \> 25% of bone marrow (such as, pelvic or abdominal radiation) within 30 days prior to randomization * Participant has participated in clinical trials of experimental agents within 4 weeks prior to randomization * Participant has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders * Participant has active, high risk bleeding (such as, via gastric ulcers or gastric varices) within 14 days prior to randomization * Participant has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy * Participant has uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator * Participant has brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease * Participant has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness * Participant has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen. * Participant is pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months) | PFS was defined as time from randomization until the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter of target lesions taking as reference the smallest sum longest diameter since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). Participants who neither progressed nor died were censored the day of their last radiographic tumor assessment if available or date of randomization if no post initiation radiographic assessment was available. If death or PD occurred after ≥2 missing radiographic visits, censoring occurred at date of the last radiographic visit prior to the missed visits. The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months) | TTP was defined as the time from the date of randomization to the first documented date of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). Participants who did not progress were censored at the last radiographic tumor assessment. If no post-baseline assessment was available censoring occurred at the date of randomization. If PD occurred after 2 or more missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits. The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression. |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate) | Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months) | Objective response rate (ORR) was defined as the percentage of randomized participants achieving a best confirmed overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), based on the achievement of both measurement and confirmation criteria; by Investigator assessment. CR was defined as the disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum LD and no progression in non-target lesions. |
| Duration of Response | Date of first CR or PR to PD or death or until data cutoff date of 31-Mar-2013 (up to 56 months) | Duration of complete response (CR) or partial response (PR) measured from time criteria were first met for CR or PR until first date of progressive disease (PD) or death from any cause defined using Response Evaluation Criteria in Solid Tumor (RECIST 1.0); by Investigator assessment. CR defined as disappearance of all target and non-target lesions. PR defined as ≥30% decrease in sum of longest diameter (LD) of target lesions and no progression in non-target lesions. PD defined as ≥20% increase in LD sum of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of ≥1 new lesion(s). Participants who did not relapse or die censored at day of last radiographic tumor assessment. If death or PD was after ≥2 missing radiographic visits, censoring was at date of last radiographic visit prior to missed visits. Symptomatic/clinical disease progression without documented radiologic progression did not constitute progression. |
| Overall Survival (OS) | Randomization to death or until data cutoff of 29-May-2015 (up to 82 months) | OS was defined as the duration from randomization to death from any cause. Participants who were alive at data cut-off for the OS analysis or lost to follow-up were censored on the last date the participant was known to be alive. |
| Number of Participants With Adverse Events | First dose to study completion (up to 12.3 years) | Clinically significant events were defined as serious adverse events (SAE) and other treatment-emergent non-serious adverse events (NSAE). A summary of SAEs and other NSAEs is located in the Reported Adverse Event module. |
| Immunogenicity: Percentage of Participants With Treatment Emergent Anti-Ramucirumab Antibodies Until Primary Data Cutoff of 31-Mar-2013 | Baseline, prior to cycle 3 infusion, prior to cycle 5 infusion, onset of infusion reaction, resolution of reaction and 30 days following the event up to 56 months | Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study. Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals. |
| Immunogenicity: Percentage of Participants Available After 31-Mar-2013 With Treatment Emergent Anti-Ramucirumab Antibodies Until Data Cutoff From 01-Apr-2013 to 08-Sep-2016 | Follow-up from 01-Apr-2013 to 08-Sep-2016 (Up to 56 -97 months) | Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study. Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals. |
| Total Functional Assessment of Cancer Therapy-Breast (FACT-B): Change From Baseline to End of Therapy | Baseline, End of Therapy or until data cutoff of 31-Mar-2013 (up to 56 months) | FACT-B measures the following domains of health-related quality of life (HR-QoL): physical well-being (PWB), social/family well-being (SFWB), emotional well-being (EWB), functional well-being (FWB), and additional concerns of breast cancer subscale (BCS) each with 6 or more items developed to measure problems specific to breast cancer symptoms plus additional items related to global QoL. Participants respond to each of the 36 questions on a 5-point scale from 0 (not at all) to 4 (very much) with a total scores range of 0-144. Higher scores indicate fewer symptoms and better HR-QoL. |
Countries
Australia, Belgium, Brazil, Canada, Croatia, Czechia, Egypt, Germany, Ireland, Israel, Lebanon, New Zealand, Peru, Poland, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
Participants who were alive and completed the follow-up period or who died were considered to have completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Ramucirumab (IMC-1121B) + Docetaxel Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. | 759 |
| Placebo + Docetaxel Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle. | 385 |
| Total | 1,144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 47 | 18 |
| Overall Study | Withdrawal by Subject | 54 | 20 |
Baseline characteristics
| Characteristic | Ramucirumab (IMC-1121B) + Docetaxel | Total | Placebo + Docetaxel |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 130 Participants | 190 Participants | 60 Participants |
| Age, Categorical Between 18 and 65 years | 629 Participants | 954 Participants | 325 Participants |
| Age, Continuous | 53.9 years STANDARD_DEVIATION 10.5 | 54.0 years STANDARD_DEVIATION 10.4 | 54.2 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 69 Participants | 111 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 690 Participants | 1033 Participants | 343 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 51 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 41 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 22 Participants | 31 Participants | 9 Participants |
| Race (NIH/OMB) White | 676 Participants | 1017 Participants | 341 Participants |
| Region of Enrollment Australia | 28 Participants | 49 Participants | 21 Participants |
| Region of Enrollment Belgium | 48 Participants | 68 Participants | 20 Participants |
| Region of Enrollment Brazil | 30 Participants | 50 Participants | 20 Participants |
| Region of Enrollment Canada | 83 Participants | 129 Participants | 46 Participants |
| Region of Enrollment Czechia | 4 Participants | 7 Participants | 3 Participants |
| Region of Enrollment Egypt | 9 Participants | 12 Participants | 3 Participants |
| Region of Enrollment Germany | 12 Participants | 17 Participants | 5 Participants |
| Region of Enrollment Ireland | 8 Participants | 10 Participants | 2 Participants |
| Region of Enrollment Israel | 16 Participants | 23 Participants | 7 Participants |
| Region of Enrollment Lebanon | 24 Participants | 38 Participants | 14 Participants |
| Region of Enrollment New Zealand | 5 Participants | 11 Participants | 6 Participants |
| Region of Enrollment Peru | 12 Participants | 16 Participants | 4 Participants |
| Region of Enrollment Poland | 12 Participants | 17 Participants | 5 Participants |
| Region of Enrollment Russia | 210 Participants | 309 Participants | 99 Participants |
| Region of Enrollment Serbia | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Slovakia | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment South Africa | 41 Participants | 63 Participants | 22 Participants |
| Region of Enrollment South Korea | 14 Participants | 21 Participants | 7 Participants |
| Region of Enrollment Spain | 118 Participants | 182 Participants | 64 Participants |
| Region of Enrollment Taiwan | 4 Participants | 6 Participants | 2 Participants |
| Region of Enrollment United Kingdom | 21 Participants | 31 Participants | 10 Participants |
| Region of Enrollment United States | 58 Participants | 79 Participants | 21 Participants |
| Sex: Female, Male Female | 759 Participants | 1144 Participants | 385 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 737 / 752 | 373 / 382 |
| serious Total, serious adverse events | 285 / 752 | 117 / 382 |
Outcome results
Primary
Progression-Free Survival (PFS)
PFS was defined as time from randomization until the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter of target lesions taking as reference the smallest sum longest diameter since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). Participants who neither progressed nor died were censored the day of their last radiographic tumor assessment if available or date of randomization if no post initiation radiographic assessment was available. If death or PD occurred after ≥2 missing radiographic visits, censoring occurred at date of the last radiographic visit prior to the missed visits. The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression.
Time frame: Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months)
Population: Intent-to-Treat (ITT) Population: All randomized participants. Censored participants: ramucirumab + docetaxel=231, placebo + docetaxel=94.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab (IMC-1121B) + Docetaxel | Progression-Free Survival (PFS) | 9.5 months |
| Placebo + Docetaxel | Progression-Free Survival (PFS) | 8.2 months |
p-value: 0.07795% CI: [0.75, 1.01]Stratified Log Rank (SLR)
Secondary
Duration of Response
Duration of complete response (CR) or partial response (PR) measured from time criteria were first met for CR or PR until first date of progressive disease (PD) or death from any cause defined using Response Evaluation Criteria in Solid Tumor (RECIST 1.0); by Investigator assessment. CR defined as disappearance of all target and non-target lesions. PR defined as ≥30% decrease in sum of longest diameter (LD) of target lesions and no progression in non-target lesions. PD defined as ≥20% increase in LD sum of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of ≥1 new lesion(s). Participants who did not relapse or die censored at day of last radiographic tumor assessment. If death or PD was after ≥2 missing radiographic visits, censoring was at date of last radiographic visit prior to missed visits. Symptomatic/clinical disease progression without documented radiologic progression did not constitute progression.
Time frame: Date of first CR or PR to PD or death or until data cutoff date of 31-Mar-2013 (up to 56 months)
Population: A subset of the Intent-to-Treat (ITT) Population: all randomized participants with CR or PR. Censored participants: ramucirumab + docetaxel=80, placebo + docetaxel=28.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab (IMC-1121B) + Docetaxel | Duration of Response | 8.4 months |
| Placebo + Docetaxel | Duration of Response | 8.1 months |
p-value: 0.1595% CI: [0.67, 1.06]Stratified Log Rank (SLR)
Secondary
Immunogenicity: Percentage of Participants Available After 31-Mar-2013 With Treatment Emergent Anti-Ramucirumab Antibodies Until Data Cutoff From 01-Apr-2013 to 08-Sep-2016
Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study. Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals.
Time frame: Follow-up from 01-Apr-2013 to 08-Sep-2016 (Up to 56 -97 months)
Population: All follow-up participants (additional participants who were available after primary data cut off 31-Mar-13) who received at least 1 dose of study drug with anti-IMC-1121B antibodies samples collected during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab (IMC-1121B) + Docetaxel | Immunogenicity: Percentage of Participants Available After 31-Mar-2013 With Treatment Emergent Anti-Ramucirumab Antibodies Until Data Cutoff From 01-Apr-2013 to 08-Sep-2016 | 0 percentage of participants |
| Placebo + Docetaxel | Immunogenicity: Percentage of Participants Available After 31-Mar-2013 With Treatment Emergent Anti-Ramucirumab Antibodies Until Data Cutoff From 01-Apr-2013 to 08-Sep-2016 | 0 percentage of participants |
Secondary
Immunogenicity: Percentage of Participants With Treatment Emergent Anti-Ramucirumab Antibodies Until Primary Data Cutoff of 31-Mar-2013
Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study. Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals.
Time frame: Baseline, prior to cycle 3 infusion, prior to cycle 5 infusion, onset of infusion reaction, resolution of reaction and 30 days following the event up to 56 months
Population: All randomized participants who received at least 1 dose of study drug with anti-IMC-1121B antibodies samples collected during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab (IMC-1121B) + Docetaxel | Immunogenicity: Percentage of Participants With Treatment Emergent Anti-Ramucirumab Antibodies Until Primary Data Cutoff of 31-Mar-2013 | 0.8 percentage of participants |
| Placebo + Docetaxel | Immunogenicity: Percentage of Participants With Treatment Emergent Anti-Ramucirumab Antibodies Until Primary Data Cutoff of 31-Mar-2013 | 0.8 percentage of participants |
Secondary
Number of Participants With Adverse Events
Clinically significant events were defined as serious adverse events (SAE) and other treatment-emergent non-serious adverse events (NSAE). A summary of SAEs and other NSAEs is located in the Reported Adverse Event module.
Time frame: First dose to study completion (up to 12.3 years)
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ramucirumab (IMC-1121B) + Docetaxel | Number of Participants With Adverse Events | Participants with SAEs | 285 participants |
| Ramucirumab (IMC-1121B) + Docetaxel | Number of Participants With Adverse Events | Participants with NSAEs | 737 participants |
| Placebo + Docetaxel | Number of Participants With Adverse Events | Participants with SAEs | 117 participants |
| Placebo + Docetaxel | Number of Participants With Adverse Events | Participants with NSAEs | 373 participants |
Secondary
Overall Survival (OS)
OS was defined as the duration from randomization to death from any cause. Participants who were alive at data cut-off for the OS analysis or lost to follow-up were censored on the last date the participant was known to be alive.
Time frame: Randomization to death or until data cutoff of 29-May-2015 (up to 82 months)
Population: Intent-to-Treat (ITT) Population: All randomized participants. Censored participants: ramucirumab + docetaxel=267, placebo + docetaxel=121.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab (IMC-1121B) + Docetaxel | Overall Survival (OS) | 30.3 months |
| Placebo + Docetaxel | Overall Survival (OS) | 28.7 months |
p-value: 0.48795% CI: [0.81, 1.1]Stratified Log Rank (SLR)
Secondary
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate)
Objective response rate (ORR) was defined as the percentage of randomized participants achieving a best confirmed overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), based on the achievement of both measurement and confirmation criteria; by Investigator assessment. CR was defined as the disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as reference the baseline sum LD and no progression in non-target lesions.
Time frame: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
Population: Intent-to-Treat (ITT) Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ramucirumab (IMC-1121B) + Docetaxel | Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate) | 44.7 percentage of participants |
| Placebo + Docetaxel | Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate) | 37.9 percentage of participants |
p-value: 0.02795% CI: [1.03, 1.71]Stratified Cochran-Mantel-Haenszel(SCMH)
Secondary
Time to Progression (TTP)
TTP was defined as the time from the date of randomization to the first documented date of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). Participants who did not progress were censored at the last radiographic tumor assessment. If no post-baseline assessment was available censoring occurred at the date of randomization. If PD occurred after 2 or more missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits. The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression.
Time frame: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
Population: Intent-to-Treat (ITT) Population: All randomized participants. Censored participants: ramucirumab + docetaxel=263, placebo + docetaxel=104.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ramucirumab (IMC-1121B) + Docetaxel | Time to Progression (TTP) | 9.7 months |
| Placebo + Docetaxel | Time to Progression (TTP) | 8.2 months |
p-value: 0.03395% CI: [0.73, 0.99]Stratified Log Rank (SLR)
Secondary
Total Functional Assessment of Cancer Therapy-Breast (FACT-B): Change From Baseline to End of Therapy
FACT-B measures the following domains of health-related quality of life (HR-QoL): physical well-being (PWB), social/family well-being (SFWB), emotional well-being (EWB), functional well-being (FWB), and additional concerns of breast cancer subscale (BCS) each with 6 or more items developed to measure problems specific to breast cancer symptoms plus additional items related to global QoL. Participants respond to each of the 36 questions on a 5-point scale from 0 (not at all) to 4 (very much) with a total scores range of 0-144. Higher scores indicate fewer symptoms and better HR-QoL.
Time frame: Baseline, End of Therapy or until data cutoff of 31-Mar-2013 (up to 56 months)
Population: A subset of Intent-to-Treat (ITT) Population: all randomized participants with a valid baseline and end of therapy assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramucirumab (IMC-1121B) + Docetaxel | Total Functional Assessment of Cancer Therapy-Breast (FACT-B): Change From Baseline to End of Therapy | -6.8 units on a scale | Standard Deviation 17.3 |
| Placebo + Docetaxel | Total Functional Assessment of Cancer Therapy-Breast (FACT-B): Change From Baseline to End of Therapy | -7.0 units on a scale | Standard Deviation 16.8 |
p-value: 0.539ANCOVA