Phase III trial of intraperitoneal therapy with yttrium-90-labeled HMFG1 murine monoclonal antibody in patients with epithelial ovarian cancer after a surgically defined complete remission.
OBJECTIVE
This was a multinational, open-label, randomized phase III trial comparing yttrium-90-labeled murine HMFG1 (90Y-muHMFG1) plus standard treatment versus standard treatment alone in patients with epithelial ovarian cancer (EOC) who had attained a complete clinical remission after cytoreductive surgery and platinum-based chemotherapy.


METHODS
In total, 844 International Federation of Gynecology and Obstetrics stage Ic to IV patients were initially screened, of whom 447 patients with a negative second-look laparoscopy (SLL) were randomly assigned to receive either a single dose of 90Y-muHMFG1 plus standard treatment (224 patients) or standard treatment alone (223 patients). Patients in the active treatment arm received a single intraperitoneal dose of 25 mg of 90Y-muHMFG1 (target dose 666 MBq/m2). The primary end point was length of survival; secondary end points included time to relapse and safety. The study had an 80% power to detect a 15% change in survival.


RESULTS
After a median follow-up of 3.5 years (range, 1 to 6 years), 70 patients had died in the active treatment arm compared with 61 patients in the control arm. Cox proportional hazards analysis of survival demonstrated no difference between treatment arms. In the study drug arm, 104 patients experienced relapse compared with 98 patients in the standard treatment arm. No difference in time to relapse was observed between the two study arms. Active therapy was associated with occasional grade 3 or 4 thrombocytopenia and neutropenia and grade 1 or 2 GI symptoms, abdominal discomfort, arthralgia, and myalgia. CONCLUSION A single IP administration of 90Y-muHMFG1 to patients with EOC who had a negative SLL after primary therapy did not extend survival or time to relapse.
Verheijen
René H
RH
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, VU University Medical Center, Amsterdam, The Netherlands. r.verheijen@vumc.nl
Massuger
Leon F
LF
Benigno
Benedict B
BB
Epenetos
Agamemnon A
AA
Lopes
Alberto
A
Soper
John T
JT
Markowska
Janica
J
Vyzula
Rostislav
R
Jobling
Tom
T
Stamp
Gordon
G
Spiegel
Gregory
G
Thurston
Dennis
D
Falke
Theo
T
Lambert
Joanna
J
Seiden
Michael V
MV
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D010535:Laparoscopy; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D016016:Proportional Hazards Models; D012074:Remission Induction; D024162:Second-Look Surgery; D017211:Treatment Failure; D015021:Yttrium Radioisotopes
D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; C469215:pemtumomab