Table 1. Summary of ASCO 2017 gynecologic oncology trials.

Factor	First author	Trial and eligibility	Agent	Endpoints	Results	AEs
Surgical interventions	Harter P Abstract 5500	LION (NCT00712218) - Randomized prospective; primary ovarian cancer, FIGO IIB–IV	Surgical intervention	1°: OS	Median OS: LNE 65.5 mo vs. No-LNE 69.2 mo (HR=1.06; 95% CI=0.83–1.34; p=0.650)	LNE a/w longer surgery time, increased blood loss, increased transfusion rates, increased re-laparotomy rates, infections, and mortality within 60 days of surgery.
				2°: PFS, QOL	Median PFS: 25.5 mo in both arms (HR=1.11; 95% CI=0.92–1.34)
	Du Bois A Abstract 5501	AGO DESKTOP III/ENGOT ov20 (NCT01166737) - Randomized phase III interim analysis; platinum-sensitive recurrent ovarian cancer after 1st-line treatment week/+AGO score	Platinum-based cytotoxic therapy; surgical intervention	1°: OS	OS: data still maturing	No excess mortality within the surgical arm and among the grade 3/4 AEs that occurred within 60 days, only leukopenia/neutropenia was more frequent in the no-surgery arm.
				2°: PFS, TFST	Median PFS: 14 mo without and 19.6 mo with surgery (HR=0.66; 95% CI=0.52–0.83; p<0.001); with complete resection, the median PFS is 21.2 mo (HR=0.56 vs. no-surgery arm; p<0.001)
					TFST: 21 mo without vs. 13.9 mo with surgery (HR=0.61; 95% CI=0.48–0.77; p<0.001)
CT/RT	de Boer SM Abstract 5502	PORTEC-3 (NCT00411138) - Randomized phase III; high risk endometrial cancer	Platinum-based cytotoxic therapy+RT	1°: OS, FFS	5-yr OS: 82% for CTRT vs. 77% for RT (HR=0.79; 95% CI=0.57–1.12; p=0.183)	Most common grade 3 or >AEs between both groups are hematological, gastrointestinal, or related to pain. The only significant difference between the 2 groups was with sensory/motor neuropathy that was seen more frequently in the chemo-radiaton group (grade 2).
					5-yr FFS: 76% for CTRT vs. 69% for RT (HR=0.77; 95% CI=0.58–1.03; p=0.078)
					Patients with stage III disease:
					5-yr FFS: 69% for CTRT vs. 58% for RT (95% CI=0.45–0.97; p=0.032)
					5-yr OS: 79% for CTRT vs. 70% for RT (HR=0.69; 95% CI=0.44–1.09; p=0.114)
	Matei D Abstract 5505	GOG 258 (NCT00942357) - Randomized phase III; stage III–IVA (<2 cm residual disease) or stage I–II serous or clear cell endometrial cancer	Platinum-based cytotoxic therap+RT	1°: RFS	RFS: vaginal recurrence 3% for CTRT vs. 7% for CT (HR=0.36; 95% CI=0.16–0.82), pelvic and para-aortic recurrences 10% for CTRT vs. 21% for CT (HR=0.43; 95% CI=0.28–0.66); distant recurrences more common with 28% for CTRT vs. 21% for CT (HR=1.36; 95% CI=1.00–1.86)	Common greater than grade 3 events were myelosupression (40% vs. 52%), gastrointestinal (13% vs. 4%), metabolic (15% vs. 19%), neurological (7% vs. 6%), and infectious (4% vs. 5%).
				2°: OS, toxicities, QOL	OS: data still maturing; but 5-yr OS estimated 70% CTRT and 73% CT
Anti-angiogenics	Ledermann JA Abstract 5506	ICON6 (NCT00532194) - Double-blind, placebo-controlled phase III — OS results; platinum-sensitive recurrent ovarian cancer after 1st-line treatment	Cedirinib VEGFRi	1°: OS	OS: 19.9 mo in placebo and 27.3 mo in maintenance (HR=0.85; 95% CI=0.66–1.10; p=0.210)	Diarrhea, neutropenia, hypertension, and voice changes were more common with CT+cediranib, and diarrhea, hypothyroidism, and voice changes were more common during maintenance cedirinib.
				2°: PFS	Median PFS: 8.7 mo in placebo and 11.0 mo in maintenance (HR=0.56; 95% CI-=0.44–0.70; p<0.001)
	Lheureux S Abstract 5522	Princess Margaret phase II consortium (NCT01914510) - Phase II; recurrent clear cell ovarian cancer	ENMD-2076 Aurora A kinase/tyrosine kinase inhibitor	1°: ORR, 6-mo PFS	Median PFS: 3.7 mo (95% CI=3.4–4.4); in ARID1A loss was 4.1 mo (95% CI=3.5–10.3) vs. ARID1A positive 3.6 mo (95% CI=1.7–3.9) (p=0.024); in PTEN no change in PFS	Most common AEs were hypertension, nausea, and diarrhea.
	Dhani NC Abstract 5524	Princess Margaret, Chicago, and California phase II consortia; PHL86 (NCT01935934) - Single-arm phase II; recurrent/metastatic endometrial cancer	Cabozantinib Multi-target kinase inhibitor	1°: RR, 12-wk PFS	Median PFS: 4.8 mo (95% CI=4.4–6.4) with estimated 6-mo PFS of 43% (95% CI=27%–59%)	Most common toxicities were fatigue, nausea, diarrhea, and hand-foot syndrome. Most frequent grade 3/4 toxicity was hypertension.
				2°: OS; baseline molecular status of archival tumor	Mutational analysis: KRAS with PTEN or PIK3CA mutations in 9 serous/endometrioid patients, 8/9 met 12-wk PFS endpoint, with a median PFS 5.9 mo (95% CI=4.1–15.4)
PARPi	Friedlander M Abstract 5507	SOLO-2 (NCT01874353) - HRQOL analysis for patients in phase III SOLO-2 trial; platinum-sensitive recurrent BRCA+ovarian cancer after 2nd-line treatment with CR or PR	Olaparib PARPi	1°: FACT-O TOI	FACT-O TOI: no detrimental effect on QOL for maintenance therapy with olaparib vs. placebo (−2.90 vs. −2.87; 95% CI=−2.19–2.13; p=0.980)	Nausea, fatigue, vomiting, diarrhea, and abdominal pain. Heme AEs of anemia, neutropenia, and thrombocytopenia.
				2°: duration of QOL by TWiST and QAPFS	TWiST: 13.5 mo with olaparib vs. 7.2 mo with placebo (95% CI=2.9–8.6; p<0.001)
					QAPFS: mean 14.0 mo with olaparib vs. 7.3 mo with placebo (95% CI=5.0–8.5; p<0.001)
	Ledermann JA Abstract 5518	SOLO-2 (NCT01874353) - Randomized phase III — AEs; platinum-sensitive recurrent BRCA +ovarian cancer after 2nd-line treatment with CR or PR	Olaparib PARPi	1°: AEs	AEs of fatigue/asthenia, vomiting, and nausea improved as treatment continued, though could last for several months	Most common AEs with olaparib were grade 1–2 and included; nausea, fatigue/asthenia, anemia, and vomiting. Anemia was the most common grade ≥3.
				2°: safety and tolerability	Most AEs were manageable by supportive treatment, dose interruptions (olaparib, 45%; placebo, 18%) and dose reductions (olaparib, 25%; placebo, 3%)
	Wolford JE Abstract 5516	Kauffmen et al, Study 10 & ARIEL2, NOVA Cost effective analysis; recurrent ovarian cancer	Niraparib, Rucaparib, Olaparib PARPi	1°: cost-effectiveness (cost vs. PFS)	Cost-effectiveness: platinums ($1,672/PFS mo), non-platinums ($6,688/mo), bevacizumab ($12,482/mo), olaparib ($16,469/mo), rucaparib ($16,781/mo), and niraparib ($18,157/mo with mutation and $18,253/mo without mutation)	AEs were factored into the model within the heme complication and non-heme complications nodes of the Markov Model.
				2°: ICERs
	Mirza MR Abstract 5517	NOVA (NCT0184724) - Randomized, controlled, double-blind, phase III — PR analysis; platinum-sensitive recurrent ovarian cancer with PR- ≥2 prior lines	Niraparib PARPi	1°: PFS	49% of patients in the BRCAmut and non-BRCAmut cohorts entered NOVA with a PR following the most recent platinum	Most common AEs were thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue, and decreased appetite.
				2°: OS, PFS2, CT-free interval, HRQOL	PFS events: BRCAmut 45% niraparib vs. 72% placebo patients non-BRCAmut; 56% niraparib and 80% placebo patients in the cohorts
	Del Campo JM Abstract 5560	NOVA (NCT0184724) - Randomized, controlled, double-blind, phase III — platinum resistant analysis; platinum-sensitive recurrent ovarian cancer with PR — ≥2 prior lines	Niraparib PARPi	1°: PFS (randomization-death or progressive disease) → estimated probability of disease progression after 6 mo	Platinum-reistant rates (in placebo arm):	Most common AEs were thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue, and decreased appetite.
					BRCAmut: 42%
					non-BRCAmut: 53%
					combined: 49%
	Matulonis UA Abstract 5534	NOVA (NCT0184724) - Randomized, controlled, double-blind, phase III — long-term benefit; platinum-sensitive recurrent ovarian cancer with PR — ≥2 prior lines	Niraparib PARPi	1°: PFS	Estimated probability PFS at 24 mo:	Most common AEs were thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue, and decreased appetite.
				2°: impact on subsequent therapy (PFS2-PFS1)	BRCAmut: 0.42 (95% CI=0.30–0.55) for niraparib vs. 0.16 (0.07–0.28) for placebo
					non-BRCAmut 0.27 (0.19–0.35) for niraparib vs. 0.12 (0.06–0.21) for placebo
					PFS2-PFS1: similar in the 2 treatment groups
	Friedlander M Abstract 3013	The Safety, Pharmacokinetics and Antitumor Activity of the BGB-A317 in Combination With the BGB-290 in Subjects With Advanced Solid Tumors (NCT02660034) - Phase 1/1b; advanced solid tumors (ovarian, breast, prostate, gastric, bladder, pancreatic, and small cell lung cancers)	BGB-A317 Anti-PD-1 immunotherapy BGB-290 PARPi	1°: MTD, RP2D	MTD: BGB-A317 200 mg IV q 3 wk + BGB-290 40 mg PO BID 38 patients were treated → decreased tumor burder in 16, PR in 7 (ovary, uterine, pancreatic) and 1 CR (ovary)	Most common AEs was fatigue; Immune-related AEs reported were hypophysitis and autoimmune hepatitis.
				2°: preliminary anti-tumor activity, pharmokinectics profile
Immunotherapy	Varga A Abstract 5513	KEYNOTE-028 (NCT02054806) - Nonrandomized, multi-cohort phase Ib trial — 15.5-mo follow-up; platinum resisteant ovarian cancer; PD-L1 positivity	Pembrolizumab Anti-PD-1 immunotherapy	1°: safety and tolerability	ORR: 11.5% (95% CI=2.4%–30.2%)	Most common were arthralgia, nausea, pruritus, rash, and diarrhea.
				2°: confirmed ORR	Tumor reduction: 6/26 (23.1%) of patients
					Median PFS: 1.9 mo (95% CI=1.8–3.2)
					OS: 13.1 mo (95% CI=6.7–17.5)
	Hollebecque A Abstract 5504	CheckMate 358 (NCT02488759) - Single-arm, multi-cohort; phase I/II; recurrent/metastatic HPV-associated cancers	Nivolumab Anti-PD-1 immunotherapy	1°: ORR, safety	ORR at 31 wk: 21% and disease control rate (ORR+stable disease) 71%	Immune-mediated reactions: enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy.
				2°: DOR, PFS, OS	Median PFS: 5.5 mo (95% CI=3.5–not reached)
					OS: data still maturing, but median OS at 6 mo was 87%
	Schellens JH Abstract 5514	KEYNOTE-158 (NCT02628067) - Single-arm, multi-cohort phase II — preliminary results; advanced cervical squamous cell cancer with progression or intolerance to standard therapy	Pembrolizumab Anti-PD-1 immunotherapy	1°: ORR	ORR: 17% (95% CI=8%–31%)	Most common were arthralgia, nausea, pruritus, rash, and diarrhea.
				2°: DOR, safety/efficacy	ORR at ≥27 wk: 27% (95% CI=8%–55%)
Anti-hormone	Knipprath-Mészáros AM Abstract 5515	Aromatase inhibitor maintenance therapy in high grade advanced ovarian cancer to delay first recurrence Non-randomized, controlled trial; primary ovarian cancer; (FIGO III–IV), ER+, after adjuvant CT	Letrozole Aromatase inhibitor	1°: PFS	PFS at 12 mo: 65% without and 84% with letrozol	Not reported.
					PFS at 24 mo: 46% without and 74% with letrozol (p=0.020)

a/w, associated with ; AE, adverse event; AGO, Arbeitsgemeinschaft Gynäkologische Onkologie; ASCO, American Society of Clinical Oncology; CI, confidence interval; CR, complete response; CT, chemotherapy; CTRT, chemotherapy and radiation therapy; DOR, duration of response; ER, estrogen receptor; FACT-O TOI, Functional Assessment of Cancer Therapy-Ovarian Trial Outcome Index; FFS, failure-free survival; FIGO, International Federation of Gynecology and Obstetrics; GOG, Gynecologic Oncology Group; HPV, human papillomavirus; HR, hazard ratio; HRQOL, health-related quality of life; HRD, human resources division; ICER, incremental cost-effectiveness ratio; LION, lymphadenectomy in ovarian neoplasms; LN, lymph node; LNE, lymphadenectomy; MTD, maximum-tolerated dose; ORR, overall response rate; OS, overall survival; PARPi, poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor; PD-L1, programmed death-ligand 1; PD-1, programmed death-1; PFS, progression-free survival; PORTEC, Postoperative Radiation Therapy in Endometrial Carcinoma; PR, partial response; QAPFS, quality-adjusted progression-free survival; QOL, quality of life; RFS, recurrence-free survival; RP2D, recommended phase II dose; RR, response rate; RT, radiation therapy; SOLO, studies of olaparib in ovarian cancer; TFST, time to start of first subsequent therapy; TWiST, time without symptoms of disease or toxicity of treatment; VEGFRi, vascular endothelial growth factor receptor inhibitor.