Vinorelbine plus 3-weekly trastuzumab in metastatic breast cancer: a single-centre phase 2 trial.
BACKGROUND
After two studies reporting response rates higher than 70% in HER2-positive metastatic breast cancer with weekly trastuzumab and vinorelbine, we planned a phase 2 study to test activity of the same combination, with trastuzumab given every 3 weeks.


METHODS
Patients with HER2-positive metastatic breast cancer (3+ at immunohistochemistry or positive at fluorescence in situ hybridization), PS < or =2, normal left-ventricular ejection fraction (LVEF) and no more than one chemotherapy line for metastatic disease were eligible. Vinorelbine (30 mg/m2) was given on days 1 & 8 every 21 and trastuzumab (8 mg/kg day 1, then 6 mg/kg) every 21 days). A single-stage phase 2 design, with p0 = 0.45, p1 = 0.65, type I and II error = 0.10, was applied; 22 objective responses were required in 39 patients.


RESULTS
From Nov 2002 to May 2005, 50 patients were enrolled, with a median age of 54 years (range 31-81). Among 40 patients eligible for response assessment, there were 7 complete and 13 partial responses (overall response rate 50%; 95% exact CI 33.8-66.2); 11 patients had disease stabilization, lasting more than 6 months in 10 cases. Response rate did not vary according to patients and tumor characteristics, type and amount of previous chemotherapy. Within the whole series, median progression-free survival was 9.6 months (95% CI 7.3-12.3), median overall survival 22.7 months (95% CI 19.5-NA). Fifteen patients (30%) developed brain metastases at a median time of 12 months (range 1-25). There was one toxic death due to renal failure in a patient receiving concomitant pamidronate. Twenty-three patients (46%) had grade 3-4 neutropenia, 2 (4%) grade 3 anemia, 4 (8%) febrile neutropenia. Two patients stopped treatment because of grade 2 decline of LVEF and one patient because of grade 2 liver toxicity concomitant with a grade 1 decline of LVEF. One patient stopped trastuzumab after 50 cycles because of grade 1 decline of LVEF.


CONCLUSIONS
Although lower than in initial studies, activity of 3-weekly trastuzumab plus vinorelbine fell within the range of results reported with weekly schedules. Toxicity was prevalently manageable. This combination is safe and active for metastatic breast cancer patients who received adjuvant taxanes with anthracyclines.
De Maio
Ermelinda
E
Clinical Trials Unit, National Cancer Institute, Via M, Semmola, I-80131 Naples, Italy. linda.demaio@uosc.fondazionepascale.it <linda.demaio@uosc.fondazionepascale.it>
Pacilio
Carmen
C
Gravina
Adriano
A
Morabito
Alessandro
A
Di Rella
Francesca
F
Labonia
Vincenzo
V
Landi
Gabriella
G
Nuzzo
Francesco
F
Rossi
Emanuela
E
Silvestro
Pasqualina
P
Botti
Gerardo
G
Di Bonito
Maurizio
M
Curcio
Maria Pia
MP
Formichelli
Franca
F
La Vecchia
Franca
F
Staiano
Maria
M
Maurea
Nicola
N
D'Aiuto
Giuseppe
G
D'Aiuto
Massimiliano
M
Thomas
Renato
R
Signoriello
Giuseppe
G
Perrone
Francesco
F
de Matteis
Andrea
A
D015746:Abdominal Pain / Q000139:chemically induced; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003248:Constipation / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014747:Vinblastine; D000068878:Trastuzumab; D000077235:Vinorelbine