Gastric Cancer
Conditions
Brief summary
This randomized, open-label, multicenter, international Phase IIIb study will compare the efficacy and safety of two Herceptin dosing regimens in combination with cisplatin/capecitabine chemotherapy in participants with HER2-positive metastatic gastric or gastro-esophageal junction adenocarcinoma. Participants who have not received prior treatment for metastatic disease will be randomized to receive Herceptin intravenously as either an 8-milligram per kilogram (mg/kg) loading dose followed by 6 mg/kg every 3 weeks (q3w) as standard of care or an 8-mg/kg loading dose followed by 10 mg/kg q3w until disease progression. Capecitabine will be administered for 6 cycles at a dose of 800 milligrams per meter-squared (mg/m\^2) orally twice a day on Days 1 to 14 of each 3-week cycle, and cisplatin will be administered intravenously for 6 cycles at a dose of 80 mg/m\^2 on Day 1 of each 3-week cycle. Herceptin will be continued until disease progression occurs.
Interventions
DRUGCapecitabine
Capecitabine will be administered at a dose of 800 mg/m\^2 orally twice daily for 14 days q3w for up to 6 cycles (Cycles 1 to 6).
DRUGCisplatin
Cisplatin will be administered at a dose of 80 mg/m\^2 intravenously q3w on Day 1 of each 3-week cycle for up to 6 cycles (Cycles 1 to 6).
DRUGHerceptin
Herceptin will be administered at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 or 10 mg/kg (depending upon treatment assignment) q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with metastatic disease documented to involve at least liver or lung or both * Measurable disease according to RECIST Version 1.1 or non-measurable evaluable disease * At least 2 organs involved in metastatic gastric tumor (including at least lung or liver or both) in addition to the site of primary tumor, where metastasis in distant lymph nodes, peritoneal metastasis, and malignant pleural effusion may count as organs in this context * HER2-positive primary or metastatic tumor as assessed by central laboratory * Adequate renal function (creatinine clearance greater than equal to (≥) 45 milliliters per minute \[mL/min\]) * Eastern Cooperative Oncology Group (ECOG) performance status of 2
Exclusion criteria
* Previous chemotherapy for locally advanced or metastatic disease * Prior gastrectomy (partial or total) for the underlying malignant disease under investigation * Prior therapy with an anti-HER2 agent and/or platinum-based chemotherapeutic agent * Residual relevant toxicity resulting from previous therapy * Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome (such as jejunostomy probe and gastric or jejunostomy tubes) which may impair the ability to administer or absorb capecitabine * Current (significant or uncontrolled) gastrointestinal bleeding * Other malignancy within the last 5 years, except for carcinoma in situ of the cervix and basal or squamous cell carcinoma of the skin * History of documented congestive heart failure, angina pectoris requiring medication, electrocardiogram (ECG) evidence of transmural myocardial infraction, poorly controlled hypertension, clinically significant valvular heart disease, or high-risk uncontrollable arrhythmias * Baseline left ventricular ejection fraction (LVEF) less than (\<) 50%, documented by echocardiography, multiple-gated radionuclide angiography (MUGA) scan, or cardiac magnetic resonance imaging (MRI) * Chronic or high-dose corticosteroid therapy * History or clinical evidence of brain metastases * Pregnant women * Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C, or HIV-seropositive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Died - FAS | From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015) | The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the FAS with available data. |
| Overall Survival - FAS | From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015) | Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the FAS using the Kaplan-Meier approach. The 95 percent (%) confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Progression or Death - PPS | From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015) | Disease progression was defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including Baseline (nadir). In addition to the relative increase of 20%, the sum was also required to demonstrate an absolute increase of ≥5 millimeters (mm). The percentage of participants who died or experienced disease progression as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS. |
| Progression-Free Survival - PPS | From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015) | Progression-free survival was defined as the time between the day of randomization and the date of first documentation of disease progression or date of death, whichever occurred first, measured following RECIST Version 1.1 criteria. Disease progression was defined as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including Baseline (nadir). In addition to the relative increase of 20%, the sum was also required to demonstrate an absolute increase of ≥5 mm. The 95% CI for median was computed using the method of Brookmeyer and Crowley. |
| Percentage of Participants Who Died - Per Protocol Set (PPS) | From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015) | The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS. |
| Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Day 21 of Cycle 1, 2, 3, 4, 5, 7, 9, 11 (cycle length = 21 days) | Cmin samples were obtained in all participants randomized to receive Herceptin (FAS). The observed Cmin was recorded, averaged among all participants, and expressed in μg/mL. |
| Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS | Pre-dose (0 minutes) and within 15 minutes after end of 2-hour Herceptin infusion on Day 1 of Cycle 1 (cycle length = 21 days) | Trastuzumab serum concentration samples were obtained in all participants randomized to receive Herceptin (FAS). The observed concentration values were recorded, averaged among all participants, and expressed in μg/mL. |
| Percentage of Participants With Objective Response - PPS | From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015) | Objective response was defined as the occurrence of either a complete response (CR) or partial response (PR) as determined by RECIST Version 1.1 based on investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) were required to have reduction in short axis to \<10 mm. PR was defined as a ≥30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. The 95% CI was constructed using Blyth-Still-Casella method. |
| Overall Survival - PPS | From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015) | Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the PPS using the Kaplan-Meier approach. The 95% CI for median was computed using the method of Brookmeyer and Crowley. |
Countries
Australia, Bosnia and Herzegovina, Brazil, Chile, China, Czechia, Germany, Hungary, Italy, Mexico, New Zealand, Panama, Peru, Philippines, Poland, Portugal, Russia, Serbia, South Africa, South Korea, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 248 participants (124 participants per arm) were randomized in the study up to data cutoff date of 13 February 2015, and 48 additional participants (24 participants per arm) were randomized between data cutoff date of 13 February 2015 and end of study (25 August 2015) for additional safety data.
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 6 mg/kg q3w as standard of care from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m\^2 intravenously q3w plus capecitabine 800 mg/m\^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6). | 148 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) Participants received Herceptin at a loading dose of 8 mg/kg on Day 1 of Cycle 1 followed by 10 mg/kg q3w from Day 1 of Cycle 2 until disease progression, occurrence of unacceptable toxicity, or withdrawal from the study for another reason (cycle length = 21 days). Participants also received cisplatin 80 mg/m\^2 intravenously q3w plus capecitabine 800 mg/m\^2 orally twice daily for 14 days q3w for up to 6 treatment cycles (Cycles 1 to 6). | 148 |
| Total | 296 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 77 | 84 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Never Treated | 1 | 1 |
| Overall Study | Non-Compliance | 1 | 0 |
| Overall Study | Study Terminated by Sponsor | 53 | 58 |
| Overall Study | Withdrawal by Subject | 13 | 2 |
Baseline characteristics
| Characteristic | Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Total |
|---|---|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 10.6 | 62.4 years STANDARD_DEVIATION 10.7 | 60.0 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 32 Participants | 37 Participants | 69 Participants |
| Sex: Female, Male Male | 116 Participants | 111 Participants | 227 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 123 / 147 | 122 / 147 |
| serious Total, serious adverse events | 35 / 147 | 38 / 147 |
Outcome results
Primary
Overall Survival - FAS
Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the FAS using the Kaplan-Meier approach. The 95 percent (%) confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.
Time frame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Population: FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Overall Survival - FAS | 12.485 months |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Overall Survival - FAS | 10.612 months |
Comparison: Stratified analysis included stratum of creatinine clearance (45 to 59 milliliters per minute \[mL/min\] and greater than or equal to \[≥\] 60 mL/min). Hazard ratio was estimated by Cox regression.p-value: 0.240195% CI: [0.86, 1.78]Log Rank
Comparison: Unstratified analysis. Hazard ratio was estimated by Cox regression.p-value: 0.128595% CI: [0.92, 1.88]Log Rank
Primary
Percentage of Participants Who Died - FAS
The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the FAS with available data.
Time frame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Population: FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Percentage of Participants Who Died - FAS | 46.8 percentage of participants |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Percentage of Participants Who Died - FAS | 54.0 percentage of participants |
Secondary
Overall Survival - PPS
Overall survival was defined as the time from the date of randomization to the date of death from any cause. Overall survival was estimated among participants from the PPS using the Kaplan-Meier approach. The 95% CI for median was computed using the method of Brookmeyer and Crowley.
Time frame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Population: PPS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Overall Survival - PPS | 10.809 months |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Overall Survival - PPS | 9.363 months |
Comparison: Stratified analysis included stratum of creatinine clearance (45 to 59 mL/min and ≥60 mL/min). Hazard ratio was estimated by Cox regression.p-value: 0.993195% CI: [0.49, 2.04]Log Rank
Comparison: Unstratified analysis. Hazard ratio was estimated by Cox regression.p-value: 0.945895% CI: [0.52, 2.02]Log Rank
Secondary
Percentage of Participants Who Died - Per Protocol Set (PPS)
The percentage of participants who died as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS.
Time frame: From date of randomization until death or premature withdrawal (up to approximately 31 months or data cutoff date of 13 February 2015)
Population: The PPS included all participants who were found to have a trastuzumab minimum plasma concentration (Cmin) less than (\<) 12 micrograms per milliliter (μg/mL) on treatment Day 21 of Cycle 1 following the initial loading dose of 8 mg/kg.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Percentage of Participants Who Died - Per Protocol Set (PPS) | 51.5 percentage of participants |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Percentage of Participants Who Died - Per Protocol Set (PPS) | 59.4 percentage of participants |
Secondary
Percentage of Participants With Disease Progression or Death - PPS
Disease progression was defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including Baseline (nadir). In addition to the relative increase of 20%, the sum was also required to demonstrate an absolute increase of ≥5 millimeters (mm). The percentage of participants who died or experienced disease progression as of the analysis data cutoff date of 13 February 2015 was reported among participants from the PPS.
Time frame: From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)
Population: PPS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Percentage of Participants With Disease Progression or Death - PPS | 75.8 percentage of participants |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Percentage of Participants With Disease Progression or Death - PPS | 81.3 percentage of participants |
Secondary
Percentage of Participants With Objective Response - PPS
Objective response was defined as the occurrence of either a complete response (CR) or partial response (PR) as determined by RECIST Version 1.1 based on investigator assessment. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) were required to have reduction in short axis to \<10 mm. PR was defined as a ≥30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters. The 95% CI was constructed using Blyth-Still-Casella method.
Time frame: From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)
Population: PPS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Percentage of Participants With Objective Response - PPS | 57.6 percentage of participants |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Percentage of Participants With Objective Response - PPS | 50.0 percentage of participants |
Comparison: The 95% CI for difference in response rates was constructed using the normal approximation to the binomial distribution.p-value: 0.540295% CI: [-31.75, 16.6]Chi-squared
95% CI: [0.28, 1.96]
Secondary
Progression-Free Survival - PPS
Progression-free survival was defined as the time between the day of randomization and the date of first documentation of disease progression or date of death, whichever occurred first, measured following RECIST Version 1.1 criteria. Disease progression was defined as a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including Baseline (nadir). In addition to the relative increase of 20%, the sum was also required to demonstrate an absolute increase of ≥5 mm. The 95% CI for median was computed using the method of Brookmeyer and Crowley.
Time frame: From date of randomization until first occurrence of disease progression or death; assessed every 6 weeks (up to approximately 31 months or data cutoff date of 13 February 2015)
Population: PPS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Progression-Free Survival - PPS | 5.388 months |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Progression-Free Survival - PPS | 4.370 months |
Comparison: Stratified analysis included stratum of creatinine clearance (45 to 59 mL/min and ≥60 mL/min). Hazard ratio was estimated by Cox regression.p-value: 0.675995% CI: [0.63, 2.02]Log Rank
Comparison: Unstratified analysis. Hazard ratio was estimated by Cox regression.p-value: 0.576495% CI: [0.67, 2.05]Log Rank
Secondary
Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS
Cmin samples were obtained in all participants randomized to receive Herceptin (FAS). The observed Cmin was recorded, averaged among all participants, and expressed in μg/mL.
Time frame: Day 21 of Cycle 1, 2, 3, 4, 5, 7, 9, 11 (cycle length = 21 days)
Population: FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure. Here also, n reflects the number of participants who were evaluable for each category in the respective arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 1 (n=100,99) | 17.1 μg/mL | Standard Deviation 14.3 |
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 2 (n=93,76) | 19.2 μg/mL | Standard Deviation 8.8 |
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 3 (n=77,71) | 23.2 μg/mL | Standard Deviation 11.8 |
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 4 (n=73,61) | 25.9 μg/mL | Standard Deviation 12.1 |
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 5 (n=70,60) | 26.7 μg/mL | Standard Deviation 10.6 |
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 7 (n=51,44) | 31.4 μg/mL | Standard Deviation 14.2 |
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 9 (n=31,24) | 33.7 μg/mL | Standard Deviation 17.6 |
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 11 (n=24,16) | 32.5 μg/mL | Standard Deviation 14.7 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 11 (n=24,16) | 68.4 μg/mL | Standard Deviation 35.9 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 1 (n=100,99) | 18.1 μg/mL | Standard Deviation 18.1 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 5 (n=70,60) | 49.3 μg/mL | Standard Deviation 23.2 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 2 (n=93,76) | 35.3 μg/mL | Standard Deviation 19.4 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 9 (n=31,24) | 61.0 μg/mL | Standard Deviation 23.9 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 3 (n=77,71) | 40.7 μg/mL | Standard Deviation 20.6 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 7 (n=51,44) | 58.1 μg/mL | Standard Deviation 27.6 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Trastuzumab Cmin on Day 21 of Cycles 1 to 11 - FAS | Cycle 4 (n=73,61) | 47.6 μg/mL | Standard Deviation 20.2 |
Secondary
Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS
Trastuzumab serum concentration samples were obtained in all participants randomized to receive Herceptin (FAS). The observed concentration values were recorded, averaged among all participants, and expressed in μg/mL.
Time frame: Pre-dose (0 minutes) and within 15 minutes after end of 2-hour Herceptin infusion on Day 1 of Cycle 1 (cycle length = 21 days)
Population: FAS population. Here, number of participants analyzed reflects the number of participants who were evaluable for this outcome measure. Here also, n reflects the number of participants who were evaluable for each category in the respective arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS | Pre-dose (n=109,110) | 0.168 μg/mL | Standard Deviation 1.69 |
| Capecitabine + Cisplatin + Herceptin (6 mg/kg) | Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS | End of infusion (n=110,111) | 126 μg/mL | Standard Deviation 59.6 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS | Pre-dose (n=109,110) | 0.0204 μg/mL | Standard Deviation 0.123 |
| Capecitabine + Cisplatin + Herceptin (10 mg/kg) | Trastuzumab Serum Concentration on Day 1 of Cycle 1 - FAS | End of infusion (n=110,111) | 137 μg/mL | Standard Deviation 55.7 |