Introduction/Background There is an unmet need to develop effective regimens for the treatment of advanced or recurrent endometrial cancer and a strong biological rationale to investigate anti-angiogenic agents and PARP inhibitors in this disease.

Methodology Patients with advanced/recurrent endometrial cancer after one prior line of platinum-based chemotherapy and ECOG Performance status 0–1 were randomised 1:1:1 to weekly paclitaxel (80mg/m2 on days 1, 8 and 15 of a 28-day cycle for 6 cycles) without (PaW) or with cediranib (PaC) (20mg OD) or olaparib (300mg BD) with cediranib (20mg OD) (OC). Cediranib and olaparib were continued until progression or intolerable toxicity. Primary endpoint was percentage of patients free from progression at 3 months (3mo PFS). Secondary endpoints included response rate (RR), median progression-free survival (PFS), toxicity and quality of life (QoL).

Results 124 patients were randomised and 116 were evaluable for the primary analysis. Median age was 66.5 years (range 31.1–83.5). Histological subtype: G1/2 endometrioid 20%; G3 endometrioid 27%; serous 34%; carcinosarcoma 14%; other 5%.

Three-month PFS was 51.3% (PaW), 52.6% (OC), but 76.9% (PaC: odds ratio vs PaW 3.5 (lower limit 95%CI 2.1, one-sided p=0.02). RRs were 28.2% (PaW), 23.1% (OC), but 56.4% (PaC: odds ratio 5.7 vs PaW (95% CI 1.8–17.6, p<0.001)). Median PFS was 5.4 months (m) (PaW), 4.3m (OC) and 6.9m (PaC). 22% (PaW), 54% (OC), 61% (PaC) of patients experienced grade 3 or 4 treatment-emergent adverse events (TEAEs). The most prevalent G3+ TEAEs were fatigue (2.4%/9.8%/7.3%) (PaW/OC/PaC), hypertension (0%/2.4%/14.6%) and diarrhoea (0%/0%/9.8%). However, only 4 (9.8%) PaC patients and 1 (2.4%) OC patient withdrew due to G3+ TEAEs. The greatest beneficial impact on functioning QoL was seen in the OC arm.

Conclusion The addition of cediranib to weekly paclitaxel significantly improved 3-month PFS and RR in patients with advanced/recurrent endometrial cancer previously treated with platinum.

Disclosures Andrew R Clamp declares receipt of grants/research supports institutional funding with AstraZeneca, Merck, Advenchen, Eisai, Verastem, and Novartis. Receipt of honoraria or consultation fees for GSK, Clovis, Immunogen and MSD. Participation in a company sponsored speaker’s bureau with GSK. Angela Casbard declares receipt of grants/research supports with AstraZeneca. Marcia Hall declares receipt of grants/research supports with BMS, Clovis Oncology and Merck. Educational grants and receipt of honoraria or consultation fees with Clovis Oncology and Immunogen. Gemma Eminowicz declares consultation fees with MSD. Angela George declares receipt of honoraria or consultation fees with AZD, GSK, MSD and Roche. Participation in a company sponsored speaker’s bureau with GSK. Axel Walther declares receipt of honoraria or consultation fees with AstraZeneca and GSK. Louise Hanna declares other support with Roche and Mims and Tesara. Rene Roux declares receipt of honoraria or consultation fees with Novartis and GSK. Participation in a company sponsored speaker’s bureau with Pfizer, GSK, Lilly and AstraZeneca. Other support with MSD supporting an Oxford Gynaecology away day. Rosemary Lord declares AstraZeneca support for COMICE Investigator lead study and GSK honoraria speakers bureau. Joey Wood declares receipt of honoraria or consultation fees for GSK and Clovis. Rebecca Bowen declares receipt of honoraria or consultation fees with GSK, AstraZeneca, Clovis and Eisai. Rebecca Kristeleit declares receipt of grants/research supports with InCyte for funding for translational research sample storage. Receipt of honoraria or consultation fees with Duke St Bio, Eisai, MSD, AZ, GSK, Clovis Oncology/Pharma &, Basilea, Seattle Genetics, Tubulis, Shattuck Labs, Prokarium, Leucid, Celcuity and iTEOS. Participation in a company sponsored speaker’s bureau with Eisai, MSD, Astra Zeneca and GSK. Gordon C Jayson declares receipt of grants/research supports with AstraZeneca and stock shareholder with Sanofi and Bionntech. The remaining authors declare no potential conflict of interests.