Phase-II study of weekly schedule of trastuzumab, paclitaxel, and carboplatin followed by a week off every 28 days for HER2+ metastatic breast cancer.
BACKGROUND
Addition of carboplatin (C) to trastuzumab (T) and paclitaxel (P) improves the efficacy in HER2+ metastatic breast cancer (MBC). The aim of this phase-II study was to evaluate the efficacy and safety of this combination given weekly (3x) followed by a week off. The primary endpoint was: objective response rate (ORR), and secondary endpoints were: time to progression (TTP), overall survival (OS), and toxicity profile.


METHODS
HER2+ MBC patients were included in the study. Treatment was as follows: T (loading dose:4 mg/kg per week and 2 mg/kg per day thereafter), P (80 mg/m(2)) and C (AUC 2) given weekly 3x, followed by 1 week off until disease progression or unacceptable toxicity.


RESULTS
Forty-one patients (pts) were enrolled-median age: 54.5 years (range 29-75); 87.8% PS 0 or 1; 39 (97.5%) had received prior adjuvant or neoadjuvant treatment; 11 (27%) had received one prior CT line for metastatic disease; disease sites: liver (40%), bone (32.5%), lymph nodes (32.5%) and lung (20%); 19 (47.5%) had > or =2 lesions and 97.5% had measurable disease. A total of 37 pts were evaluated for response: 11(26.8%) CR; 12 (29.3%) PR; 9 (22%) SD; 5 (12.2%) PD and 4 NE, resulting in an ORR of 56.1% (95% CI 39.7-71.5%) and tumor growth control rate (RR + SD) of 78% (95% CI 62.4-89.4%). With a median follow up of 39.4 months, 26 (70.3%) patients have progressed. The median time to progression was 12.3 months (95% CI 8.2-15.5). At the time of this report, ten patients have died. Forty patients received 202 cycles (median five cycles). Grades 3-4 toxicities/pts: 3 (7.5%) anemia, 2 (5%) leucopenia, 10 (25%) neutropenia, 1 (2.5%) febrile neutropenia,1 (2.5%) thrombopenia, 2 (5%) asthenia, 2 (5%) diarrhea, 3 (7.5%) nausea, 2 (5%) vomiting, and 3 (7.5%) mucositis.


CONCLUSIONS
The schedule showed an interesting activity, taking into account that 27% of patients had received previous treatment for MBC. One week of rest may benefit not only the patient but may also improve tolerability and efficacy of the combination.
Ruiz
M
M
Hospital Virgen del Rocio, Seville, Spain.
Salvador
J
J
Bayo
J
J
Lomas
M
M
Moreno
A
A
Valero
M
M
Bernabé
R
R
Vicente
D
D
Jiménez
J
J
Lopez-Ladrón
A
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D018734:Genes, erbB-2; D006207:Half-Life; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016019:Survival Analysis; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D000068878:Trastuzumab; D017239:Paclitaxel