Review Article

Targeting the Epidermal Growth Factor Receptor in Epithelial Ovarian Cancer: Current Knowledge and Future Challenges

Table 2

Summary of clinical trials using EGFR inhibitors in ovarian cancers References are in parentheses next to the first author of the study. CT: clinical trial; IHC: immunohistochemistry; RPPA: reverse phase protein array; CR: complete response; PR: partial response; SD: stable disease; pt: patient; PFS: progression free survival; GOG: Gynecologic Oncology Group; VEGFR: vascular endothelial growth factor receptor.
(a) Monoclonal Antibodies

Study and YearCT no.Phase# PtsTherapySelection criteriaOutcomeComments

Secord et al. 2008 [97]NCT 00086892II28Cetuximab + CarboplatinRecurrent, platinum-sensitive diseaseCR: 3 ptsResponse rate criteria not met for next stage of accrual. 26 pts were EGFR positive by IHC.
PR: 6 pts
SD: 8 pts
Konner et al. 2008 [98]NCT 00063401II40Cetuximab + Paclitaxel + CarboplatinGrade III-IV debulked tumor, EGFR positive by IHCMedian PFS: 14.4 monthsCombination was adequately tolerated. No increase in PFS when compared to historical data.
PFS at 18 months: 39%
Schilder et al. 2009 [96]II25CetuximabPersistent or recurrent ovarian or primary peritoneal disease, EGFR positive tumors by IHC12 serologic markers examined before and during treatment. No correlation between PFS and marker changes, but high baseline of markers associated with earlier disease progression.
PR: 1 pt
SD: 9 pts
Seiden et al. 2007 [99]NCT 00073541II37MatuzumabRecurrent platinum-refractory disease, EGFR positivity by IHCNo objective responsePrimary objective was pharmacodynamic; signal transduction evaluation. 75 pts were screened for EGFR status.
SD: 16%–22%
Bookman et al. 2003 [101]GOG-160II41TrastuzumabPersistent and/or refractory disease with 2-3+ HER2 by IHCCR: 1 ptSerum HER2 levels not associated with clinical outcome.
PR: 2 pts

(b) Small Molecule Inhibitors

Study and YearCT no.Phase# PtsTherapySelection criteriaOutcomeComments

Posadas et al. 2007 [203]NCT 00049556II24GefitinibPlatinum-refractory diseaseNo objective responseProtein correlates done with RPPA. No significant correlation between EGFR phosphorylation and tumor response
SD: 37% for >2 months
Schilder et al. 2005 [112]NCT 00023699II27GefitinibPersistent or recurrent diseasePR: 1 ptAnalyses suggest trend towards responsiveness in EGFR positive (by IHC) pts. Activating mutations documented in the PR pt.
Wagner et al. 2007 [115]NCT 00189358II56Gefitinib + TamoxifenDisease refractory or resistant to platinum-taxane-based therapyNo objective responseEGFR positivity not a prerequisite; EGFR status not determined
SD: 16 pts
Gordon et al. 2005 [116]II34ErlotinibRelapsed or progressive disease, EGFR positivity by IHCPR: 2 ptsPrimary goal was to estimate the objective tumor response rate to erlotinib as a single agent.
SD: 15 pts
Vasey et al. 2008 [118]Ib45Erlotinib + Docetaxel + CarboplatinChemonaïve ptsCR: 5 ptsPhase Ib dose finding study. Addition of erlotinib to other agents did not increase response rate.
PR: 7 pts
(23 evaluable)
Nimeiri et al. 2008 [117]NCT 00126542II13Erlotinib + BevacizumabRecurrent or refractory disease, ≤2 prior cytotoxic chemotherapies; no previous anti-EGFR or VEGFR therapiesNo indication of improvement over bevacizumab treatment only. No EGFR mutations detected; one EGFR 2+ IHC staining detected.
CR: 1 pt
PR: 1 pt
Kimball et al. 2008 [122]NCT 00317434I11Lapatinib + CarboplatinRecurrent, platinum-sensitive diseasePR: 3 ptsNo screening or measurement of EGFR or HER2 performed.
SD: 3 pts
Campos et al. 2005 [123]II105CI-1033Relapsed or refractory diseaseNo objective responseBaseline HER1-2 levels determined by IHC. No association between HER levels and SD.
SD: 26–34%