Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Fluorouracil

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Methotrexate

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Participants with HER2 proto-oncogene positive breast cancer (HER2+) were treated with trastuzumab 8 milligrams per kilogram (mg/kg), intravenous (IV), on Day 1 of Cycle 1, followed by 6 mg/kg, IV, on Day 1 of Cycle 2 to up a maximum of Cycle 17. Participants also received doxorubicin 60 mg/ square meter (m\^2), IV, and paclitaxel 150 mg/m\^2, IV, on Day 1 of Cycles 1 through 3. Followed by paclitaxel 175 mg/m\^2, IV, alone on Day 1 of Cycles 4 through 7. Participants also received CMF: cyclophosphamide 600 mg/m\^2, IV; methotrexate 40 mg/m\^2, IV; and 5-fluorouracil 600 mg/m\^2, IV, on Day 1 of Cycles 8 through 10.

Participants with HER2 proto-oncogene positive breast cancer were treated with doxorubicin 60 mg/m\^2, IV, and paclitaxel 150 mg/m\^2, IV, on Day 1 of Cycles 1 through 3. Followed by paclitaxel 175 mg/m\^2, IV, alone on Day 1 of Cycles 4 through 7. Participants also received CMF on Day 1 of Cycle 8 through 10.

Participants with HER2 proto-oncogene negative breast cancer were treated with doxorubicin 60 mg/m\^2, IV, and paclitaxel 150 mg/m\^2, IV, on Day 1 of Cycles 1 through 3. Followed by paclitaxel 175 mg/m\^2, IV, alone on Day 1 of Cycles 4 through 7. Participants also received CMF on Day 1 of Cycle 8 through 10.

8mg/kg IV on Day 1 of Cycle 1, followed by 6 mg/kg on Day 1 of Cycle 2 up a maximum of Cycle 17

60 mg/m2 IV on Day 1 of Cycles 1 through 3

150 mg/m2 IV on Day 1 of Cycles 1 through 3, followed by 175 mg/m2 IV on Day 1 of Cycles 4 through 7

CMF: Cyclophosphamide (600 mg/m2 IV bolus), methotrexate (40 mg/m2 IV bolus), 5-fluorouracil (600 mg/m2 IV bolus) on Day 1 of Cycles 8 through 10

Clinical Trials

This study will assess the efficacy and safety of adding Herceptin to a paclitaxel-containing regimen followed by cyclophosphamide/methotrexate/fluorouracil (CMF) chemotherapy in women with locally advanced breast cancer and HER2/c-erbB-2 gene amplification. In a parallel observational study patients with HER2-negative disease will receive the same chemotherapy without Herceptin.

A Study of Herceptin (Trastuzumab) in Combination Chemotherapy in Women With Locally Advanced Breast Cancer

A Randomized, Open-label Study of the Effect of Paclitaxel, Doxorubicin, and CMF Neoadjuvant Chemotherapy, With and Without Herceptin, on Tumor Response in Women With HER2-positive Breast Cancer

EFS was defined as the time between randomization and date of documented occurrence of disease recurrence or progression (local, regional, distant or contralateral) or death due to any cause.

The median time, in months, between randomization and date of documented occurrence of an EFS event.

bpCR was defined as an absence of any invasive cancer cell of the primary tumor at the time of major surgery after neoadjuvant chemotherapy with and without trastuzumab.

tpCR was defined as a determination of bpCR and an absence of positive axillary nodes on pathology.

Assessments were made based on objective tumor measurements of the lesions as recorded in the case report form. In inflammatory cancer, progressive disease (PD) was defined as progression of any of the 2 signs of breast edema and erythema. In non-inflammatory cancer, PD was concluded if either the investigator judged the participant as having progressed at any time prior to surgery, or there was at least a 20% increase in the sum of target lesions (TLs), any new lesion, or clear progression of any nontarget lesion (NTLs). Clear progression of any NTL was defined as at least a 20% increase in the sum of NTLs compared to BL. PR was defined as at least a 30% decrease from BL in the sum of the longest diameter of TLs. CR was defined as no PD as assessed by the investigator and complete disappearance of all lesions.

OS was defined as the time from the date of randomization to the date of the death due to any cause.

Hoffmann-La Roche

The safety analysis population included all participants randomized in the main study or registered in the parallel observational arm who received at least 1 dose of study medication. 20 participants in the HER2+C group crossed over to receive adjuvant trastuzumab after surgery; these participants were included in the HER+C group below.

Participants with HER2+ breast cancer received treatment as follows:

Cycles 1-3 (3-week cycles): trastuzumab 8 mg/kg, IV on Day 1 (Cycle 1 only; 6 mg/kg in Cycles 2 and 3), doxorubicin 60 mg/m\^2, IV, and paclitaxel 150 mg/m\^2, IV, on Day 1 followed by 2 weeks off.

Cycles 4-7 (3-week cycles): trastuzumab 6 mg/kg, IV, paclitaxel 175 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 8-10 (3-week cycles): trastuzumab 6 mg/kg, IV, cyclophosphamide 600 mg/m\^2, IV, methotrexate 40 mg/m\^2, IV, and 5-fluorouracil 600 mg/m\^2, IV, (collectively CMF) on Day 1, followed by 2 weeks off.

Cycles 11-17 (3-week cycles): postoperatively, participants received trastuzumab 6 mg/kg IV on Days 1 and 8, followed by 1 week off for maximum of 17 overall cycles with trastuzumab. Adjuvant tamoxifen, 20 mg/day was administered for up to 5 years.

HER2+ TC

Participants with HER2+ breast cancer received treatment as follows:

Cycles 1-3 (3-week cycles): doxorubicin 60 mg/m\^2, IV and paclitaxel 150 mg/m\^2, IV, on Day 1 followed by 2 weeks off.

Cycles 4-7 (3-week cycles): paclitaxel 175 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 8-10 (3-week cycles): cyclophosphamide 600 mg/m\^2, IV, methotrexate 40 mg/m\^2, IV, and 5-fluorouracil 600 mg/m\^2, IV, on Days 1 and 8, followed by 1 week off.

HER2+ C

Participants with HER2- breast cancer received treatment as follows:

Cycles 1-3 (3-week cycles): doxorubicin 60 mg/m\^2, IV, and paclitaxel 150 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 4-7 (3-week cycles): paclitaxel 175 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 8-10 (3-week cycles): cyclophosphamide 600 mg/m\^2, IV, methotrexate 40 mg/m\^2, IV, and 5-fluorouracil 600 mg/m\^2, IV, on Days 1 and 8, followed by 1 week off.

HER2- C

Participants with HER2+ breast cancer received treatment as follows:

Cycles 1-3 (3-week cycles): trastuzumab 8 mg/kg, IV on Day 1 (Cycle 1 only; 6 mg/kg in Cycles 2 and 3), doxorubicin 60 mg/m\^2, IV, and paclitaxel 150 mg/m\^2, IV, on Day 1 followed by 2 weeks off.

Cycles 4-7 (3-week cycles): trastuzumab 6 mg/kg, IV, paclitaxel 175 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 8-10 (3-week cycles): trastuzumab 6 mg/kg, IV, on Day 1 and cyclophosphamide 600 mg/m\^2, IV, methotrexate 40 mg/m\^2, IV, and 5-fluorouracil 600 mg/m\^2, IV, (collectively CMF) on Days 1 and 8, followed by 2 weeks off.

Cycles 11-17 (3-week cycles): postoperatively, participants received trastuzumab 6 mg/kg IV on Day 1, followed by 2 weeks off for maximum of 17 overall cycles with trastuzumab. Adjuvant tamoxifen, 20 mg/day was administered for up to 5 years.

Total

Age, Continuous

Sex: Female, Male

Safety population: all participants who were randomized for the main study or registered for the observational parallel study and who received study medication at least once. Groups were analyzed as randomized/registered. Age was missing for 1 participant in the HER2+ TC treatment group.

Medical Communications

The full analysis set (FAS) included all participants who were randomized in the main study or registered in the parallel observational arm.

Event-Free Survival (EFS) - Percentage of Participants With an Event

Percentage of Participants With Breast Pathological Complete Response (bpCR)

Percentage of Participants With Total Pathological Complete Response (tpCR)

Percentage of Participants Achieving Either Complete Response (CR) or Partial Response (PR) According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

Overall Survival (OS) - Percentage of Participants With an Event

Participants with HER2+ breast cancer received doxorubicin, paclitaxel and CMF as follows:

Cycles 1-3 (3-week cycles): doxorubicin 60 mg/m\^2, IV and paclitaxel 150 mg/m\^2, IV, on Day 1 followed by 2 weeks off.

Cycles 4-7 (3-week cycles): paclitaxel 175 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 8-10 (3-week cycles): cyclophosphamide 600 mg/m\^2, IV, methotrexate 40 mg/m\^2, IV, and 5-fluorouracil 600 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Participants with HER2- breast cancer received doxorubicin, paclitaxel, and CMF as follows:

Cycles 1-3 (3-week cycles): doxorubicin 60 mg/m\^2, IV, and paclitaxel 150 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 4-7 (3-week cycles): paclitaxel 175 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 8-10 (3-week cycles): cyclophosphamide 600 mg/m\^2, IV, methotrexate 40 mg/m\^2, IV, and 5-fluorouracil 600 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Event-Free Survival

Percentage of Participants Event Free at 1 Year

Overall Survival

Percentage of Participants Surviving at 1 Year

Percentage of Participants Event Free at 2 Years

Percentage of Participants Surviving at 2 Years

Percentage of Participants Event Free at 3 Years

Percentage of Participants Surviving at 3 Years

Participants with human epidermal growth factor receptor 2 proto-oncogene positive (HER2+) breast cancer received treatment as follows:

Cycles 1-3 (3-week cycles): trastuzumab 8 milligrams per kilogram (mg/kg), intravenously (IV) on Day 1 (Cycle 1 only; 6 mg/kg in Cycles 2 and 3), doxorubicin 60 mg/square meter (mg/m\^2), IV, and paclitaxel 150 mg/m\^2, IV, on Day 1 followed by 2 weeks off.

Cycles 4-7 (3-week cycles): trastuzumab 6 mg/kg, IV, paclitaxel 175 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 8-10 (3-week cycles): trastuzumab 6 mg/kg, IV, on Day 1 and cyclophosphamide 600 mg/m\^2, IV, methotrexate 40 mg/m\^2, IV, and 5-fluorouracil 600 mg/m\^2, IV, (collectively CMF) on Days 1 and 8, followed by 2 weeks off.

Cycles 11-17 (3-week cycles): postoperatively, participants received trastuzumab 6 mg/kg IV on Day 1, followed by 2 weeks off for maximum of 17 overall cycles with trastuzumab. Adjuvant tamoxifen, 20 mg/day was administered for up to 5 years.

HER2+ Trastuzumab/Doxorubicin/Paclitaxel/CMF (HER2+TC)

HER2+ Doxorubicin/Paclitaxel/CMF (HER2+C)

Participants with human epidermal growth factor receptor proto-oncogene negative (HER2-) breast cancer received treatment as follows:

Cycles 1-3 (3-week cycles): doxorubicin 60 mg/m\^2, IV, and paclitaxel 150 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 4-7 (3-week cycles): paclitaxel 175 mg/m\^2, IV, on Day 1, followed by 2 weeks off.

Cycles 8-10 (3-week cycles): cyclophosphamide 600 mg/m\^2, IV, methotrexate 40 mg/m\^2, IV, and 5-fluorouracil 600 mg/m\^2, IV, on Days 1 and 8, followed by 1 week off.

Spots Global Cancer Trial Database for A Study of Herceptin (Trastuzumab) in Combination Chemotherapy in Women With Locally Advanced Breast Cancer

Trial Identification

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Study Description

Keywords

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