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Introduction/Background* Endometrial cancer (EC) patients (Pts) with advanced and recurrent disease relapse despite treatment with combination chemotherapy and have a short progression-free survival (PFS). Nintedanib (N) is a potent, orally available triple receptor tyrosine kinase inhibitor targeting VEGFR 1–3, PDGFR α/β, and FGFR 1–3. This study explored the preliminary efficacy of nintedanib in EC. Methodology The primary objective of this placebo-controlled, randomized study was to evaluate efficacy defined by median PFS of concomitant and maintenance N against placebo (P) in combination with chemotherapy. Patients with histologically confirmed stage IIIC2 or IVA & B or relapsed after adjuvant therapy for stage I-III disease; prior surgery; adjuvant chemotherapy; radiation therapy; hormonal therapy in metastatic setting; with measurable/non-measurable disease were permitted. Pts were randomized 1:1 to receive N 200mg or P, twice daily days 2–21 during chemotherapy (six cycles of Carboplatin (AUC5) and paclitaxel (175mg/m2) every 21 days) and continuously in maintenance phase. N/P was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Stratification by stage of disease, prior adjuvant chemotherapy and measurable/non-measurable disease. This is an ENGOT Model A study. Clinical trial information: NCT02730416. Result(s)* 146 of 148 pts were eligible for PFS: 72N/74P; mean age 66yrs; FIGO stage III 18%, IV 42%, recurrent 40%; follow-up 30 mo. N added to chemotherapy did not improve PFS (119 events) as compared to chemotherapy plus P: median for N 8.3 vs. for P 7.2 mo; hazard ratio (HR) adjusted for stratification factors 1.03; 95% confidence interval (CI),[0.71 to 1.48]; p0.879. Median overall survival (85 events) for N 20 vs. for P 22 mo; HR: 1.10; CI: 0.72–1.69; p0.665. Treatment-emerged grade 3–4 adverse events were higher in N vs P arm: liver function tests 13%/0%; diarrhea 12%/6%; neutropenia 21%/14%; asthenia 4%/1%. Patient-reported outcomes will be reported. Conclusion* Addition of nintedanib to chemotherapy did not improve PFS nor OS. This regimen cannot be recommended to undergo further testing in a phase III trial.

Introduction/Background* As stated by ESGO-ESMO, there is a need for indicators of chemotherapy efficacy in ovarian carcinoma patients treated in first-line setting (Colombo et al, IGCS, 2020). The pathological chemotherapy response score (CRS) and the modeled CA-125 KELIM during neo-adjuvant chemotherapy were reported as potential markers. Moreover, changes in tumor infiltrating lymphocytes (TILs) after neo-adjuvant chemotherapy were reported as a prognostic factor (Leary et al, Cancer Immunol Immunother, 2021). We studied the relationships between changes in TILs, the pathological response (pR) and KELIM in patients treated with neo-adjuvant chemotherapy +/- interval debulking surgery (IDS) from CHIVA phase II trial. Methodology The patients were enrolled in the randomized phase II trial CHIVA (NCT01583322, neo-adjuvant carboplatin-paclitaxel +/- nintedanib, +/- IDS, n=188 patients). KELIM were previously calculated (You et al CCR 2020). The 30 patients with the highest KELIM (very chemosensitive) or the lowest KELIM (poorly chemosensitive) were selected. HE-stained sections from available tissue blocks at baseline and after chemotherapy were analyzed for stromal TILs (sTILs, surface of the tumor stroma occupied by lymphocytes) and intra-epithelial TILs (ieTILs, brisk or non-brisk). The pathological response (pR) was assessed on the most tumoral available tissue block obtained after chemotherapy (good response if extensive fibrous changes with no or isolated tumor cells, or Result(s)* No relationships between KELIM and TILs infiltrates on baseline tumor samples were found. However, strong associations were found between KELIM and TIL infiltrates after neo-adjuvant chemotherapy for sTILs (median KELIM for sTILs 0-5% vs >5%: 0.28 versus 1.32, P Conclusion* High consistency was found between the modeled CA125 KELIM calculated during the first 100 days of neo-adjuvant chemotherapy and the pathological response, consistent with their values as indicators of the tumor chemosensitivity in first-line setting. Moreover, TILs changes were strongly associated with chemosensitivity, opening hypotheses about the mechanisms of chemosensitivity, and immunotherapy opportunity.

Introduction/Background* There is poor evidence from mostly retrospective series whether co-medication with metformin, statin or beta-blocker have an impact on survival in patients with primary ovarian cancer. The aim of this study was to investigate the association of these medications with survival. Methodology Individual data from 3 prospective phase III randomized controlled trials (AGO-OVAR 11/ICON 7, 12, 16) and one phase II trial (AGO-OVAR 15) were pooled and analyzed. Patients were either classified as “ever-user” if the specific co-medication was documented at least once during the trial. In. contrast, “never-users” served as controls. Data were adjusted for potential confounders (age, FIGO stage, histology, residual tumor after surgery, ECOG performance status, BMI, Charlson Comorbidity Index and assigned treatment within the trial) in multivariate Cox regression analyses. Result(s)* Overall, 2.857 patients were included in the analyses. “Ever-users” were: N=100 patients received metformin (3.5%), N=226 received statins (7.9%), and N=475 (16.6%) received beta-blockers (BB) (N=391 selective (sBB); N=84 non-selective (nsBB)) as co-medication. There were no significant differences regarding the baseline characteristics (histology, FIGO stage, residual tumor after surgery, and chemotherapy-schedule) between “ever- and never-users” except that “ever-users” were significantly older and more obese, compared to controls. Median progression-free (PFS) and overall survival (OS) for the entire cohort was 18.7 months and 60.1 months, respectively Multivariate analyses for PFS and OS including age, BMI, Histology, FIGO stage, residual tumor after surgery, ECOG performance status and CCI revealed neither a significant impact of metformin on survival of “ever-users”, compared to “never-users” (PFS HR 0.94 95%-CI 0.69-1.29, p=0.7; OS HR 0.82 95%-CI 0.58-1.17, p=0.28), nor for statins (PFS HR 0.98 95%-CI 0.82-1.18, p=0.87; OS HR 0.91 95%-CI 0.74-1.12, p=0.37), respectively. In contrast, “ever-users” of sBB had a significantly elevated risk for recurrence and death in multivariate analysis (PFS HR 1.22 95%-CI 1.05-1.41, p=0.009; OS HR 1.25 95%-CI 1.06-1.47, p=0.009). Conclusion* In this large pooled analysis neither a co-medication with metformin nor with statins had a significant impact on survival in patients with primary ovarian cancer. In contrast, co-medication with a beta-blocker was associated with worse survival. Further studies are warranted to confirm this observation.

Introduction/Background PET-CT is an imaging examination whose preoperative diagnostic value in advanced-staged ovarian cancer patients remains controversial. Main objective of this study was to answer whether performing early preoperative PET-CT scan in patients undergoing neoadjuvant chemotherapy may discriminate their response and prognosis. Methodology A prospective observational study was performed between September 2014 and May 2016. There were exclusively included patients diagnosed with advanced-stage ovarian cancer considered as not eligible for primary debulking surgery according to laparoscopy Fagotti score. These patients were treated with four cycles of neoadjuvant chemotherapy with carbotaxole followed by interval debulking and three additional cycles of chemotherapy. PET-CT was performed between the initiation of chemotherapy (T0), first (T1) and fourth cycle of chemotherapy (T4). Follow-up outcomes of patients were also recorded. Primary outcomes were SUV (Standardized Uptake Value), MTV (Metabolic Tumor Volume) and TLG (Tumor Lesion Glycolysis) that were assessed by three different blind physicians each. Total and percentage modifications of these parameters within T0,T1 and T4 were compared between patients with and without recurrence and cancer-related death, while they were also correlated with OS and DFS in a Cox regression analysis. Results τhere were 10 patients recruited for this study. All patients managed to have complete excision of the disease. SUVmax, MTV and TLG did not present significant interobserver variability within physicians. SUVmax was reduced at 45.9% between T0 and T1 in patients with later cancer-related death vs. only 8.0% in survivors (P=.05), while the relative mean decrease in absolute units was 6.5 vs 1.17 (P=.06). Similarly, TLG between T0 and T1 was reduced at 76.51% vs. 33.7% (P=.04), while mean TLG decrease was 1663.8 vs 653.8 units respectively (P=.06). In contrary, patients not presenting recurrence were characterized by significantly higher TLG reduction between T1 and T4 (95.0% for non-recurrence vs 69.1% for recurrence, P=.04), while TLG mean reduction was 1088 vs. 211 units (P=.11). Furthermore, all mean values of PET-CT parameters presented a higher reduction between T1 and T4 in patients not presenting recurrence. Conclusion PET-CT examination preoperatively in advanced-staged ovarian cancer patients may be prognostic. Further studies with larger sample size should be performed in order to assess the exact role of PET-CT scan on preoperative triage of advanced-stage ovarian cancer patients. Disclosures Authors have nothing to disclose.

Introduction/Background In SOLO1 trial, maintenance therapy with olaparib considerably improved progression-free survival (PFS) among women with newly-diagnosed, advanced BRCA-mutated HGEOC. Based on the large real-life ESME ovarian cancer (OC) cohort, we aimed to describe the patient‘s characteristics and survival outcomes of a selected cohort of BRCA-mutated patients before the era of PARP inhibitors maintenance in first line. Methodology ESME OC is a national cohort including all patients (pts) with EOC managed in the 18 French Comprehensive Cancer Centres (NCT03275298). ESME Research program collected retrospective data from patient‘s medical records. BRCA1, BRCA2, or both mutated patients with de novo diagnosed advanced (FIGO stage III or IV) high-grade serous or endometrioid EOC were eligible. Primary objective was to describe patient‘s characteristics, clinical features and treatment patterns. Results Of the 4777 patients with OC treated in first line by platinum-based chemotherapy between 2011 and 2016, 266 were included. Median age was 57.0 (33–81). 187 pts (70.3%) harbored a BRCA1 mutation, and 75 (28.2%) a BRCA2 mutation. 66.9% of patients had FIGO stage III disease. Almost all patients (95.5%) underwent surgical resection, after neoadjuvant chemotherapy (48%), or primary debulking surgery (44.9%). 119 pts (44.7%) received maintenance therapy and majority with bevacizumab alone (78.9%). After a median follow-up of 51.7months, the median PFS (mPFS) was 28.6months [95 CI: 26.2–32.4]. Patients exhibited higher mPFS in case of FIGO stage III than stage IV (32.4 months and 25.4 months, respectively), or BRCA2 mutation than BRCA1 (33.3 months and 27.7 months, respectively). Although populations were non comparable, mPFS was close between patients treated with or without maintenance (28.3 and 29.5 months, respectively). Median PFS2 were 51.4 months and 50.4 months, respectively. Estimated 5-year OS for the whole population was 69.2% [95 CI: 65.3–73.0]. Conclusion This large ESME OC cohort described clinical features and real-life survival outcomes among pts with newly diagnosed advanced BRCA-mutated HGEOC treated in specialized centres. Disclosure This work was supported by UNICANCER. The ESME OC database is supported by an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo). Data collection, analyses and publications are totally managed by R&D UNICANCER independently of the industrial consortium. All the authors declare that there is no conflict of interest regarding the publication of this article.

Introduction/Background Surgery is the cornerstone of ovarian Granulosa Cell Tumor (GCT). Complete resection with adequate staging is the gold standard in 1st line setting. The aim of this study is to assess the impact of an appropriate surgery according to the guidelines. Methodology This is a nationwide five-year retrospective study, including 463 patients (of the 639 included patients) with a definitive diagnosis of GCT between 2011 and 2016. Medical and surgical practices were analyzed for conformity. Conformity to guidelines was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysteretomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsy and peritoneal cytology) according to the FIGO classification. Results Median age at diagnosis was 49 years old (range 10–89). The median size of tumor was 94 mm (range 5–400). Radical surgery was performed in 240 patients (51,8%), while a fertility-sparing surgery was performed in 98 cases (21,2%). A complete surgical staging was performed in only 76 cases (16,4%). 289 (62.4%) patients received an evaluation of the endometrium (hysterectomy or endometrial curettage). Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (29,6%) and not assessable in 48 cases (10,4%) respectively. A statistically significant improvement in the surgical management was observed among patients treated after 2012 compared to those treated before 2012. This Improvement included: endometrial evaluation (p=0,026), tumour rupture rate during surgery (p=0,010) and the global compliance of the surgery (p Conclusion Staging surgery provides a better assessment and an appropriate treatment of this rare tumors. According to this study, the implementation of a national network and guidelines dedicated to rare gynaecologic tumors seems to significantly improve the surgical management of the patients with GCT. Disclosure Nothing to disclose.

Introduction/Background In the Phase III SOLO1 first-line trial, maintenance therapy with the PARP inhibitor olaparib provided a substantial progression-free survival (PFS) benefit to advanced ovarian cancer (OC) patients who have a BRCA1/2 mutation (BRCAm) and are in complete or partial response to first-line chemotherapy (Moore K et al. N Engl J Med 2018). VEGF inhibitor may increase PARP sensitivity, particularly in some OC patients with BRCA wild type (Liu JF et al. Lancet Oncol 2014). PAOLA-1/ENGOT-ov25 (NCT02477644) is the first Phase III trial to evaluate the efficacy and safety of a PARP inhibitor with bevacizumab as first-line maintenance therapy, and in patients regardless of BRCAm status. Methodology PAOLA-1 is a randomized, double-blind, international Phase III trial. Eligible patients had newly diagnosed, advanced (FIGO stage IIIA-IV) high-grade serous or endometrioid ovarian, fallopian tube or peritoneal cancer. Patients had no evidence of disease or were in partial response following first-line platinum-based chemotherapy plus bevacizumab. Bevacizumab was to be given for up to 15 months, including the initial combination with chemotherapy. 806 patients were randomized (2:1) in maintenance therapy to olaparib (300 mg bid) or placebo plus bevacizumab (15 mg/kg, d1, q3w), stratified by first-line treatment outcome and tumour BRCAm status. The primary endpoint is investigator-assessed PFS (modified RECIST v1.1). The 458 PFS events required for the primary analysis to show significance at the two-sided 5% level with an estimated >80% power have been reached in March 2019. Database lock was in July and analyses are ongoing. Results The LBA will report: investigator-assessed PFS, PFS by BRCAm/HRD status, health- related quality of life, and safety and tolerability results. Conclusion PAOLA-1 will demonstrate whether addition of olaparib to bevacizumab maintenance therapy following first-line platinum-based chemotherapy plus bevacizumab provides a clinically meaningful benefit to OC patients. Disclosure P Harter declares honoraria from AstraZeneca, Roche, Sotio, Tesaro, Stryker, ASCO, Zai Lab and MSD; and consultancy/advisory board fees from AstraZeneca, Roche, Tesaro, Lilly, Clovis, Immunogen and MSD/Merck. Marie Ange Mouret-Reynier declares no conflicts of interest. S Pignata declares honoraria from Roche, AstraZeneca, MSD, Pfizer, Incyte, Novartis, PharmaMar, Clovis and Tesaro; and travel expenses from Roche, AstraZeneca and MSD. Claire Cropet declares no conflicts of interest. A Gonzalez-Martin declares consulting/advisory board fees from Roche, AstraZeneca, Tesaro, Clovis, Pfizer, ImmunoGen, PharmaMar, MSD, Genmad and Novartis; and speaker bureau/expert testimony fees from Roche, AstraZeneca, MSD Tesaro and PharmaMar. Gerhard Bogner declares consulting/advisory board fees from AstraZeneca Tesaro and Roche; and travel expenses from GSK, Roche, Pharmamar, AstraZeneca and Tesaro. K Fujiwara declares honoraria from AstraZeneca, Chugai Roche, Zeria, Taiho, Nihon Kayaku, Kyowahakko Kirin, Janssen and Daiichi Sankyo; consulting/advisory board fees from Pfizer, MSD and Eisai; research funding from AstraZeneca, MSD, Chugai Roche, Eisai and Kaken; and travel expenses from Pfizer. I Vergote declares consulting/advisory board fees from Advaxis, BIOCAD, Eisai, MSD, Roche, Genmab, Roche, PharmaMar, Millenium Pharmaceuticals, Clovis, AstraZeneca, Tesaro, Oncoinvent, ImmunoGen and Sotio; contracted research with Oncoinvent and Genmab; research funding from Amgen, Roche and Stichting tegen Kanker; and Takeda Oncology, PharmaMar, Genmab, Roche, AstraZeneca, Tesaro, Clovis and Immunogen. N Colombo declares honoraria from Roche, AstraZeneca, PharmaMar, Tesaro, Clovis, Pfizer, MSD, BIOCAD and Takeda; consulting/advisory board fees from Roche, AstraZeneca, PharmaMar, Tesaro, Clovis, Pfizer, MSD, BIOCAD, Takeda; and travel expenses from PharmaMar, Tesaro and Roche. J Maenpaa declares honoraria from Roche, AstraZeneca and Tesaro; consultancy/advisory board fees from AstraZeneca, Tesaro, Clovis and MSD; and travel expenses from Roche. Anne Floquet declares consultancy/advisory board fees from GSK, AstraZeneca and Clovis; and travel expenses from Roche, GSK and AstraZeneca. Ahmed El-Balat declares honoraria from AstraZeneca, Roche, Pharmamar, MSD, Tesaro, Clovis; and consultancy/advisory board fees from AstraZeneca and Roche. D Lorusso declares honoraria from Merck; consultancy/advisory board fees from Merck, AstraZeneca, Tesaro, Clovis, Immunogen, PharmaMar and Roche; research funding from Clovis, PharmaMar, Merck and Roche; and travel expenses from Tesaro, Roche and PharmaMar. EM Guerra Alia declares consultancy/advisory board fees from Roche, Clovis and AstraZeneca; and travel expenses from Roche and Baxter. Michel Fabro declares honoraria from Tesaro and AstraZeneca; and consultancy/advisory board fees from Tesaro and AstraZeneca. Barbara Schmalfeldt declares honoraria from Roche, AstraZeneca, Tesaro, Clovis, Ethicon, MSD; consultancy/advisory fees from Roche, AstraZeneca, Tesaro, Clovis, Ethicon, MDS; speaker bureau/expert testimony fees from Roche, AstraZeneca, Tesaro, Clovis, Ethicon, MDS; research grant funding from Roche, AstraZeneca, Tesaro, Clovis, Ethicon, MDS and travel expenses from Roche, AstraZeneca, Tesaro, Clovis, Ethicon, MDS. Anne Claire Hardy Blessard declares honoraria from AstraZeneca, Lilly, Novartis, Pfizer, Roche and Tesaro. Ingo Runnebaum declares honoraria from AstraZeneca. I Ray-Coquard declares honoraria from AstraZeneca, Clovis, Tesaro and PharmaMar; consulting/advisory board fees from AstraZeneca, Roche, Clovis, Tesaro, Genmab, PharmaMar, MSD and Pfizer; research funding from MSD; and travel expenses from AstraZeneca and Roche; consulting/advisory board fees from Roche; and travel expenses from Roche, MSD, Tesaro and AstraZeneca. E Pujade-Lauraine declares honoraria from AstraZeneca and Tesaro; consulting/advisory board fees from AstraZeneca, Roche, Clovis, Tesaro, Genmab, Incyte, MSD and Pfizer; research funding from AstraZeneca, Roche and Tesaro; and travel expenses from AstraZeneca, Roche and Tesaro.

Introduction/Background In SOLO1 (NCT01844986; GOG-3004), maintenance olaparib significantly improved progression-free survival (PFS) vs placebo (HR 0.30; 95% CI 0.23–0.41; P Methodology SOLO1 recruited patients who had undergone upfront or interval cytoreductive surgery and had no residual or residual macroscopic disease. Patients were stratified by platinum response (clinical CR or PR) and received olaparib tablets 300 mg twice daily or placebo. PFS was assessed by investigators using modified RECIST v1.1. Results 260 patients were randomized to olaparib and 131 to placebo; one patient did not receive placebo. Median follow-up was 41 months in both arms. 63% and 35% of patients underwent upfront and interval surgery, respectively; 76% and 21% had no residual and residual macroscopic disease, respectively, after surgery regardless of timing; and 44% of SOLO1 patients had stage III disease, underwent upfront surgery and had no residual disease following surgery. PFS was significantly improved with olaparib, regardless of the timing of surgery or residual disease status after surgery (table 1). PFS was also significantly improved in the subgroup of patients with stage III disease who underwent upfront surgery and had no residual disease following surgery. Conclusion Maintenance olaparib improved outcomes compared with placebo in patients with newly diagnosed advanced OC and a BRCAm, regardless of the timing of surgery or residual disease status after surgery. Olaparib improved PFS in stage III patients who had undergone upfront surgery and had no residual disease, a population at high risk of progression, but typically excluded from first-line OC trials. Disclosure KM: Ad board: AZ, Advaxis, Clovis, Tesaro, Genentech/Roche, Immunogen, VBL Therapeutics, Merck, Janssen, Aravive, Pfizer, Eisai, Samumed, Oncomed. NC: Honoraria/reimbursement, speaker role/advisory board fees: AZ, Roche, Tesaro, PharmaMar; advisory board fees: Clovis, Pfizer. GS: None. B-GK: None. AO: Consulting fees: Roche, AZ, PharmaMar, Clovis, Tesaro, Immunogen, Genmab. MF: Honoraria, speaker role/advisory boards: AZ; advisory board fees: MSD, Lilly, Takeda; non-comp consulting: AbbVie. AL: None. AF: Advisory board fees: AZ, Clovis; congress support: Roche, PharmaMar; advisory board fees/congress support: Tesaro. AL: Honoraria/reimbursement, advisory board fees: AZ; advisory board fees: Clovis, Biocad; consulting fees: Seattle Genetics. GS: Research funding: AZ, Merck, Novartis, Roche. CG: Honoraria/reimbursement, consulting fees, grants: AZ, Tesaro, Nucana; honoraria/reimbursement, consulting fees: Roche, Clovis, Foundation One, MSD, Sierra Oncology; grants: Novartis, Aprea. SB: Grants, honoraria/reimbursement: AZ; honoraria/reimbursement: Tesaro, Clovis, Merck, PharmaMar, Roche, Seattle Genetics. AO: Steering committee role (non-comp): AZ, Clovis, Tesaro. AG-M: Speaker role/consulting fees: AZ, Tesaro, PharmaMar, Roche; consulting fees: Clovis, Inmunogen, Genmab, Pfizer, MSD. CA: Honoraria/reimbursement: Tesaro, ImmunoGen, Clovis. WB: None. CM: None. JL: Advisory board fees: AZ, Clovis, Mersana, Tesaro. ESL: Shareholder, employee: AZ. RB: Shareholder, employee: AZ. PD: Consulting fees: AZ, Tesaro.