Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: potential predictive relationship with tumor HER2 activation status.
OBJECTIVE
Ovarian cancers (OCs) frequently have HER2 activation in the absence of HER2 overexpression. Pertuzumab, a humanized antibody that prevents HER2 dimerization and inhibits multiple HER-mediated pathways, was studied in a phase II, multicenter trial in advanced, refractory OC.


METHODS
Sixty-one patients (cohort 1) with relapsed OC received a loading dose of 840 mg pertuzumab intravenously followed by 420 mg every 3 weeks; 62 patients (cohort 2) received 1,050 mg every 3 weeks. Response rate was the primary end point. Fresh tumor biopsies were obtained in cohort 1 to assay for phosphorylated HER2 (pHER2).


RESULTS
Median age was 57 years and median number of prior chemotherapy regimens was five. Fifty-five patients in cohort 1 and 62 patients in cohort 2 were assessable for efficacy. There were five partial responses (response rate [RR] = 4.3%; 95% CI, 1.7% to 9.4%), eight patients (6.8%) with stable disease (SD) lasting at least 6 months, and 10 patients with CA-125 reduction of at least 50% (includes two partial responses and four patients with SD > or = 6 months; total clinical activity, 14.5%). Median progression-free survival (PFS) was 6.6 weeks. Eight of 28 tumor biopsies (28.6%) were pHER2+ by enzyme-linked immunosorbent assay (ELISA; without gene amplification). Median PFS for pHER2+ patients was 20.9 weeks (n = 8) versus 5.8 weeks for pHER2- (n = 20; P = .14) and 9.1 weeks for unknown pHER2 status (n = 27). Pertuzumab was well tolerated with diarrhea in 69.1% (11.4% grade 3, no grade 4). Five patients had asymptomatic left ventricular ejection fraction decreases to less than 50% (one confirmed by central facility).


CONCLUSIONS
Pertuzumab is well tolerated with a RR of 4.3% in heavily-pretreated OC patients. Further studies on pHER2 as a diagnostic are warranted.
Gordon
Michael S
MS
Arizona Cancer Center, Tuscon and Scottsdale, AZ, USA.
Matei
Daniela
D
Aghajanian
Carol
C
Matulonis
Ursula A
UA
Brewer
Molly
M
Fleming
Gini F
GF
Hainsworth
John D
JD
Garcia
Agustin A
AA
Pegram
Mark D
MD
Schilder
Russell J
RJ
Cohn
David E
DE
Roman
Lynda
L
Derynck
Mika K
MK
Ng
Kimmie
K
Lyons
Benjamin
B
Allison
David E
DE
Eberhard
David A
DA
Pham
Thinh Q
TQ
Dere
Randall C
RC
Karlan
Beth Y
BY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C485206:pertuzumab