A phase II evaluation of lapatinib in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a gynecologic oncology group study.
OBJECTIVE
Activation and dimerization of the ERBB family play a role in the pathogenesis and progression of ovarian cancer. We conducted a phase II trial to evaluate the activity and tolerability of lapatinib in patients with recurrent or persistent epithelial ovarian cancer (EOC) and to explore the clinical value of expression levels of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER-2/neu, and Ki-67, and the presence of EGFR mutations.


METHODS
Eligible patients had recurrent or persistent EOC or primary peritoneal carcinoma, measurable disease, and up to 2 prior chemotherapy regimens for recurrent disease. Patients were treated with lapatinib 1500 mg/day. The primary endpoint of efficacy was 6-month progression free survival (PFS).


RESULTS
Twenty-five of 28 patients were eligible and evaluable for analysis of efficacy and toxicity. Two (8.0%) were alive and progression-free at 6 months. No objective responses were observed. There were 1 grade 4 toxicity (fatigue) and few grade 3 toxicities. Associations between Ki-67 with prior platinum-free interval, PFS, and a polymorphism in EGFR were suggested.


CONCLUSIONS
Lapatinib has minimal activity in recurrent ovarian cancer. Ki-67 expression may be associated with prior PFS and a polymorphism in EGFR exon 20 (2361G>A, Q787Q).
University of Southern California, Los Angeles, CA, USA. aagarcia@usc.edu
Agustin A
AA
Garcia
Michael W
MW
Sill
Heather A
HA
Lankes
Andrew K
AK
Godwin
Robert S
RS
Mannel
Deborah K
DK
Armstrong
Robert L
RL
Carolla
Marcia K
MK
Liepman
Nick M
NM
Spirtos
Edgar G
EG
Fischer
Kimberly K
KK
Leslie
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis; D000077341:Lapatinib; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D011799:Quinazolines; D000077341:Lapatinib; D066246:ErbB Receptors