Evaluation of the Effects of Pasireotide LAR Administration on Lymphocele Prevention after Axillary Node Dissection for Breast Cancer: Results of a Randomized Non-Comparative Phase 2 Study.
OBJECTIVE
The aim of this study was to assess the efficacy (response rate centered on 80%) of a somatostatin analog with high affinity for 4 somatostatin receptors in reducing the postoperative incidence of symptomatic lymphocele formation following total mastectomy with axillary lymph node dissection.


METHODS
This prospective, double-blind, randomised, placebo-controlled, phase 2 trial was conducted in two secondary care centres.


METHODS
All female patients for whom mastectomy and axillary lymph node dissection were indicated were eligible for the study, including patients who had received neo-adjuvant chemotherapy. Main exclusion criteria were related to diabetes, cardiac insufficiency, disorder of cardiac conduction or hepatic failure.


METHODS
Patients were randomised to receive one injection of either prolonged-release pasireotide 60 mg or placebo (physiological serum), which were administered intramuscularly 7 to 10 days before the scheduled surgery. The study was conducted in a double-blind manner.


METHODS
The primary outcome measure was the percentage of patients who did not develop post-operative axillary symptomatic lymphoceles during the 2 postoperative months. Secondary endpoints were the total quantity of lymph drained, duration and daily volume of drainage and aspirated volumes of lymph.


RESULTS
Ninety-one patients were randomised. Ninety patients were evaluable: 42 patients received pasireotide, and 48 patients received placebo. The mean estimated response rate were 62.4% (95% Credibility Interval [CrI]: 48.6%-75.3%) in the treatment group and 50.2% (95% CrI: 37.6%-62.8%) in the placebo group. Overall safety was comparable across groups, and one serious adverse event occurred. In the treatment group, one patient with known insulin-depe*ndent diabetes required hospitalization for hyperglycaemia.


CONCLUSIONS
With this phase 2 preliminary study, even if our results indicate a trend towards a reduction in symptomatic lymphocele, pre-operative injection of pasireotide failed to achieve a response rate centered on 80%. Pharmacokinetics analysis suggests that effect of pasireotide could be optimised.


BACKGROUND
ClinicalTrials.gov NCT01356862.
Department of Gynecology, Hôpital Tenon, Paris, France.|ED 394-Ecole Doctorale Physiologie Physiopathologie, Paris, France.|EA 3499 "Transporteurs ABC et épithéliums normaux et tumoraux," Paris, France.
Elisabeth
E
Chéreau
Department of Surgery, Gustave Roussy, Paris, France.
Catherine
C
Uzan
Department of Biostatistics, Hôpital Saint Louis, Paris, France.
Emmanuelle
E
Boutmy-Deslandes
INSERM, U1138, team 22, University Paris 5, University Paris 6, Paris, France.
Sarah
S
Zohar
Department of Gynecology, Hôpital Tenon, Paris, France.
Corinne
C
Bézu
Department of Surgery, Gustave Roussy, Paris, France.
Chafika
C
Mazouni
Department of Surgery, Gustave Roussy, Paris, France.
Jean-Rémi
JR
Garbay
Department of Gynecology, Hôpital Tenon, Paris, France.|ED 394-Ecole Doctorale Physiologie Physiopathologie, Paris, France.
Emile
E
Daraï
Department of Gynecology, Hôpital Tenon, Paris, France.|Department of Surgery, Institut Curie, Saint-Cloud, France.|EA 7285: Risques cliniques et sécurité en santé des femmes et en santé périnatale, Versailles-St-Quentin-en-Yvelines University, Montigny-le-Bretonneux, France.
Roman
R
Rouzier
D000328:Adult; D000368:Aged; D001365:Axilla; D001943:Breast Neoplasms / Q000473:pathology / Q000601:surgery*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008197:Lymph Node Excision / Q000009:adverse effects*; D008207:Lymphatic Metastasis; D008210:Lymphocele / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008408:Mastectomy / Q000009:adverse effects*; D008875:Middle Aged; D009367:Neoplasm Staging; D011183:Postoperative Complications / Q000188:drug therapy*; D011379:Prognosis; D011446:Prospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D013004:Somatostatin; C517782:pasireotide