Therapeutic targets and new directions for antibodies developed for ovarian cancer

Figures & data

Figure 1. Schematic representation of the monoclonal antibody targets for ovarian cancer. Antibodies for treatment of ovarian cancer can be targeted against tumor-associated antigens, tumor-promoting molecules produced and secreted in tumor environments, or against immune checkpoint molecules to engender immune cell activation and overcome immune tolerance supported by tumors.

Table 1. Monoclonal Antibodies for treatment of ovarian cancer

Name	Antibody	Phase 3 trial design	Outcome	References
Monoclonal antibody vaccinations
Abagovomab	Murine anti-idotypic mAb mimicking CA125	EOC in complete remission following surgery or platinum-based chemotherapy; comparing abagovomab to placebo.	Monthly maintenance injections induced immune response. No improvement in PFS or OS measured.	^75
^90Y-muHMFG1	MUC1-specific murine IgG1 (yttrium-90 labeled)	EOC; ^90Y-muHMFG1 combined with or compared to standard therapy.	No difference in time to relapse between 2 arms. No improvement in OS with ^90Y-muHMFG1.	^81
Monoclonal antibodies targeting tumor-associated antigens
Catumaxomab	EpCAM and CD3 bi-specific (trAb)	Combined with paracentesis in recurrent symptomatic malignant ascites resistant to conventional chemotherapy.	Prolonged puncture-free survival and time to next paracentesis, compared to paracentesis alone.	^85
Farletuzumab	FRα-specific humanized IgG1	Platinum-sensitive recurrent OC; comparing carboplatin/taxane treatment alone and with the addition of farletuzumab.	Improved PFS in those with lower CA125 levels.	^97
		Platinum-resistant OC; comparing paclitaxel alone, or in combination with farletuzumab.	Discontinued when the prespecified criteria for continuation were not met.	NCT00738699
Trastuzumab	HER2-specific humanized IgG1	Epithelial OC; comparing triple or doublet combinations of trastuzumab, paclitaxel and carboplatin	Ongoing trial	NCT00011986
Pertuzumab	HER2-specific humanized IgG1	Platinum-resistant recurrent OC with low HER3 mRNA expression; comparing pertuzumab combined with topotecan or paclitaxel, or comparing placebo and pertuzumab combined with topotecan, paclitaxel or gemcitabine.	On going trial	NCT01684878
Monoclonal antibodies targeting tumor-promoting molecules
Bevacizumab	VEGF-A-specific humanized IgG1	EOC, PPC and fallopian tube cancer; paclitaxel/carboplatin treatment combined with placebo, compared to concurrent bevacizumab, and concurrent plus maintenance bevacizumab.	No improvement in PFS with concurrent bevacizumab compared to chemotherapy, but increased PFS with concurrent plus maintenance bevacizumab. No difference in OS.	^126
		EOC; carboplatin and paclitaxel alone or in combination with concurrent bevacizumab.	Improved PFS was observed with chemotherapy and bevacizumab combined.	^127
		Platinum-resistant EOC; paclitaxel, PLD or topotecan alone, or combined with bevacizumab.	Improved PFS with bevacizumab in combination with chemotherapy.	^128
Monoclonal antibodies specific for immune targets
Avelumab	PD-L1-specific human IgG1	Platinum-resistant or refractory OC; comparing avelumab alone, combined with PLD, and PLD alone.	Ongoing trial	NCT02580058

EOC, epithelial ovarian cancer; PFS, progression-free survival; OS, overall survival; trAb, trifunctional antibody; OC, ovarian carcinoma; PPC, primary peritoneal cancer; PLD, pegylated liposomal doxorubicin.

Table 2. Monoclonal antibodies approved for ovarian cancer treatment

Name	Antibody	FDA approval	EMA approval	NICE approval
Catumaxumab	EpCAM and CD3 bispecific trAb	–	Treatment of EpCAM-positive ascites	Treatment of EpCAM-positive ascites
Bevacizumab	VEGF-A-specific humanized IgG1	Treatment of platinum-resistant OC	Treatment of ovarian neoplasms	i. In combination with carboplatin and paclitaxel for the treatment of advanced EOC ii. In combination with carboplatin and gemcitabine for first recurrence of platinum-sensitive EOC, FTC or PPC in patients not previously treated with bevacizumab or other VEGF-targeting agents.

FDA, US Food and Drug Administration, www.fda.gov; EMA, European Medicines Agency, www.ema.europa.eu/ema; NICE, UK National Institute for Health and Care Excellence, nice.org.uk; trAb, trifunctional antibody; OC, ovarian carcinoma; EOC, epithelial ovarian cancer; FTC, fallopian tube cancer; PPC, primary peritoneal cancer.

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