New perspectives on targeted therapy in ovarian cancer

Figures & data

Table 1 Key bevacizumab studies in epithelial ovarian cancer

Trial or author	Setting	Phase	Size	Treatment groups	Results	Gastrointestinal perforation risk
GOG^Citation19	Recurrent disease	II	62	Single group: single agent, bevacizumab (15 mg/kg every 21 days)	PFS, 4.7 months OS, 17 months 21% clinical response rate	0
Cannistra et al^Citation20	Recurrent disease	II	44	Single group: single agent, bevacizumab every 21 days	Partial response in 15.9%	11.4%
GOG 218^Citation21	First line	III	1,873	Carboplatin/paclitaxel + a. Placebo cycles 2–22 b. Bevacizumab 15 mg/kg q 3/52 cycles 2–6, then placebo cycles 7–22 c. Bevacizumab cycles 2–22	PFS group a. 10.3 months b. 11.2 months c. 14.1 months	a. 1.2% b. 2.8% c. 2.6%
ICON7^Citation22	First line	III	1,528	Carboplatin/paclitaxel ± bevacizumab, 7.5 mg/kg three times weekly	PFS, 20.3 versus 21.8 months with bevacizumab	3/750 (<0.5%) control group versus 10/735 (1%) in bevacizumab group
OCEANS^Citation25	Recurrent disease	III	484	a. Carboplatin/gemcitabine plus placebo b. Carboplatin/gemcitabine plus bevacizumab	PFS a. 8.4 months b. 12.4 months	2/242 in bevacizumab group versus 0 in nonbevacizumab group
AURELIA^Citation26	Recurrent disease	III	361	Single-agent chemotherapy (liposome doxorubicin or topotecan or weekly paclitaxel) ± bevacizumab (10 mg/kg twice weekly or 15 mg/kg q 3/52)	3.4 months PFS without bevacizumab versus 6.7 months with bevacizumab	2.2%

Abbreviations: GOG, Gynecologic Oncology Group; PFS, progression-free survival; OS, overall survival; q 3/52, every 3 weeks.

Table 2 Targeted therapeutics in type I epithelial ovarian cancer

Histology	Genetic mutation	Targeted therapy	Size	Phase	Treatment arms	Results
Low grade serous papillary	MAPK	Selumetinib (MEK1/2 inhibitor)^Citation53	52	II	Selumetinib	15% response rate. Complete response 1/52 patients
Low grade endometrioid	CTNNB1 PIK3CA PTEN KRAS BRAF	No specific trials done in patients with endometroid histology mTOR trials may have clinical utility	na	na	na	na
Mucinous carcinoma	HER2 (20%)^Citation62	Case reports of response to Trastuzumab^Citation65	na	na	na	3 patients with mucinous histology demonstrated response to trastuzumab
Clear cell carcinoma	ARID1A PIK3CA IL-6 overexpression	Sunitinib^Citation59	2	na	Sunitinib only arm	2 patients with clear cell histology demonstrated response to sunitinib

Abbreviation: na, not applicable.

Table 3 PARP inhibitors in clinical development

PARP inhibitor	Delivery	Development phase	Company
Olaparib (AZD2281, KU-0059436)	Oral	I, II, III	AstraZeneca
Veliparaib (ABT888)	Oral	I, II, III	Abbott
Rucaparib (AGO14699, AG14447, PF-0136738)	Intravenous/oral	I, II, III	Clovis Oncology, Pfizer
Niraparib (MK4827)	Oral	I, II, III	Tesaro/Merck
BMN673	Oral	I, II	Biomarin

Abbreviation: PARP, Poly(adenosine diphosphate [ADP]-ribose) polymerase.

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