Poster Display session Poster Display session

23P - Systematic Literature Review of Real-World Outcomes of Chemotherapies for Advanced or Recurrent Endometrial Cancer

Presentation Number
23P
Lecture Time
14:10 - 14:15
Speakers
  • Ananth Kadambi (Bethesda, MD, United States of America)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Prognosis in advanced or recurrent endometrial cancer (aEC) is poor (5-year overall survival [OS] 15%-17%). Paclitaxel plus carboplatin (PC) is standard of care (SOC) first-line (1L) chemotherapy (CT), and no 2L SOC is established. We conducted a systematic literature review to assess the real-world effectiveness and safety of CTs in aEC.

Methods

MEDLINE, Embase, and the Cochrane Library and five relevant conference databases (2018-2020) were searched (January 2000-July 2020) for aEC studies that met prespecified inclusion/exclusion criteria. Uterine cancer was included to capture all relevant evidence. Key outcomes included OS, progression-free survival (PFS), and adverse events (AEs).

Results

84 publications met the criteria, and most assessed outcomes in (neo)adjuvant settings. Totals of five and six studies reported OS or PFS in 1L and ≥2L, respectively. Studies were from the US (n=6), Asia (n=2), Europe (n=2), and South America (n=1), and sample sizes ranged from 20 to 3197. CTs in 1L studies included PC (n=2), taxane-based CT (n=1), platinum-based CT (n=1), or any CT (n=1); ≥2L CTs included PC (n=3), doxorubicin (n=2), or any platinum-based CT (n=1) Median OS (mOS) was reported in four of five 1L studies: 11 to 28.5 months with CT not specified, 16.9 months with taxane-based CT, and 12.5 months with PC. A median PFS (mPFS) of 5.1 months was reported in one study. All six ≥2L studies reported mOS and mPFS. Of the four studies that investigated platinum-based therapies, two provided results split by treatment-free interval (TFI). One study reported mOS as 13 months for patients with treatment-free intervals (TFI) ≥ 6 months from prior systemic therapy and 5.5 months for those with TFI < 6 months. AEs (from 3 studies) were nausea (18.9%), palmar-plantar erythrodysesthesias (16.4%), and muscle weakness (12.3%) for doxorubicin, neurotoxicity (0%-10.6%) and hypersensitivity reaction (0%-2.4%) for PC, and neutropenia (16%) for carboplatin plus epirubicin.

Conclusions

The limited evidence found low OS and PFS for aEC following CT in both 1L and ≥2L settings, further emphasizing the high unmet need for new treatment options in this aggressive indication.

Legal entity responsible for the study

Eisai Inc.

Funding

Eisai Inc.

Disclosure

All authors have declared no conflicts of interest.

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Clinical trial highlights Special session

Live Q&A

Lecture Time
11:05 - 11:15
Speakers
  • Susana Banerjee (London, United Kingdom)
Room
Auditorium 1A
Date
Sat, 18.06.2022
Time
10:30 - 12:00
GSK - Using biomarkers to guide targeted therapy in gynaecological cancers Industry satellite symposium

How and when should HRD testing guide treatment for 1L advanced ovarian cancer?

Lecture Time
13:32 - 13:49
Speakers
  • Christoph Grimm (Vienna, Austria)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
13:00 - 14:00
Poster Display session Poster Display session

12P - Any size of lymph node metastasis should be considered N1 in patients with cervical cancer

Presentation Number
12P
Lecture Time
13:20 - 13:25
Speakers
  • David Cibula (Prague, Czech Republic)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Classification of lymph node metastases according to the size into macrometastases >2 mm (MAC), micrometastases 0.2 - 2 mm (MIC) and isolated tumor cells <0.2 mm (ITC) was adopted from breast cancer to other tumour types. In cervical cancer, MAC is well established as one of the main prognostic factors, indicating adjuvant treatment after primary surgery, while the impact of MIC and ITC has been subject of controversy. The aim of this study was to identify the cut-off for the minimal size of metastasis which is not associated with negative prognosis.

Methods

Data of 967 cervical cancer patients, T1a1 L1 - T2b stages, after primary surgical treatment with curative intent, including SLN biopsy followed by pathological ultrastaging, were obtained from the SCANN (Surveillance in Cervical CANcer) study. The size of SLN metastasis was considered a continuous variable, and multiple testing was performed for cut-offs ranging from 0.01 to 1.0 mm in 0.01 mm intervals. DFS in each subgroup was compared with the N0 cohort and each N1 group (> cut-off) using Log rank test.

Results

Positive SLN was found in 172 (18%) patients. Based on traditional classification, MAC, MIC, and ITC was the largest metastasis in 79 (8%), 54 (5%), and 39 (4%) cases. Patients with MAC and MIC had significantly shorter DFS than those with N0 disease (HR 2.20, p=0.003; HR 2.87, p < 0.001) with no difference between them (p=0.484). When subgroups were analysed using cut-off method, all patients with metastases ≥0.4 mm had significantly shorter DFS when compared to the N0 (HR = 2.311; p=0.04). The significance of metastases <0.4 mm could not be assessed due to the lack of power (<80%).

Conclusions

Lymph node metastases in patients with cervical cancer are associated with significantly negative impact on DFS irrespective of their size. No cut-off value for a minimal size of metastasis without negative prognostic impact can be found. Therefore, traditional classification to MAC/MIC/ITC should not be adopted in cervical cancer and the management should be uniform irrespective of the size of metastasis.

Legal entity responsible for the study

The authors.

Funding

Charles University, Prague (UNCE 204065 and PROGRES Q28/LF1).

Disclosure

All authors have declared no conflicts of interest.

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Poster Display session Poster Display session

49P - Impact of nutritional factors in response and survival of patients with Gestational Trophoblastic Neoplasia

Presentation Number
49P
Lecture Time
16:15 - 16:20
Speakers
  • Katia Roque (Lima, Peru)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Gestational trophoblastic neoplasia (GTN) is a rare tumor with an excellent prognosis. Despite the International Federation of Gynecology and Obstetrics (FIGO) risk score, other factors that may influence survival remain unknown. We evaluated the association of nutritional predictors as body mass index (BMI), prognostic nutritional index (PNI), anemia and neutrophil/lymphocyte index (NLI) with complete response (CR) to chemotherapy and overall survival (OS).

Methods

This is a retrospective analysis of women with newly diagnosed GTN between 2005 and 2019 at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima- Peru who received chemotherapy. Clinical and baseline nutritional factors were obtained from patient files. To evaluate association with CR, we performed a Student t test and ROC curves to determine the cutoff value of variables that significantly predicted CR. Cox proportional hazards regression models were used to identify independent variables with significant influence on the OS.

Results

166 patients with GTN were included, median age was 30 years (range 18-54 y) and median FIGO risk score was 10 points (range 2-21). Accordingly, 16% and 84% of patients belong to low-risk and high-risk groups, respectively. 17 patients were lost to follow up and CR was reported in 73% of patients after first-line chemotherapy. 3y-OS was 80%, after excluding early deaths, the survival rate was 83%. About nutritional predictors, the median for BMI was 23.28, for PNI was 36.01, for hemoglobin was 10.0 and for NLI was 2.69. There was a positive association between CR with PNI and NLI (p = 0.001), no association with BMI (p = 0.389) and hemoglobin (p = 0.23) were founded. Analysis of the ROC curve for PNI demonstrated an optimal cut off value of 32.5 (p < 0.05, sensitivity 66.7, and specificity 60.6) and for NLI was 3.74 (p < 0.05, sensitivity 31.5, and specificity 51.3); the area under the ROC curve was 0.709 and 0.312 for PNI and NLI, respectively. In addition, we found a significant association with PNI (HR 0.008- CI 0.865-0.978) and NLI (HR 0.029- CI 0.807-0.989) with OS.

Conclusions

Nutritional factors such as high PNI and low NLI showed an association with OS and CR after chemotherapy.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Management of endometrial cancer in the molecular era Educational session

New treatment options for advanced and metastatic disease

Lecture Time
09:25 - 09:50
Speakers
  • Alexandra Leary (Villejuif, France)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
08:30 - 10:00
Poster Display session Poster Display session

3P - Identification of novel biomarkers of response to ATR inhibitors in ARID1A mutant ovarian clear cell carcinoma.

Presentation Number
3P
Lecture Time
12:30 - 12:35
Speakers
  • James R. Stewart (London, United Kingdom)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Ovarian clear cell carcinoma (OCCC) is characterised by a high prevalence of ARID1A mutations and chemotherapy resistance. We previously found that loss of ARID1A causes ATR inhibitor (ATRi) sensitivity, which led to the phase II ATARI clinical trial (NCT04065269). We aim to identify novel genetic determinants of ATRi response in ARID1A-mutant OCCC.

Methods

A genome wide CRISPR knockout (CRISPRn) screen was performed in OCCC TOV21G cells. CRISPR prime gene-editing was used to introduce PPP2R1A p.R183 mutations. In vitro and in vivo ATRi sensitivity was assessed in PPP2R1A isogenic models. Cell cycle analysis was performed via flow cytometry. Phospho-proteomic profiling was performed using mass spectrometry.

Results

A CRISPRn screen in ARID1A mutant OCCC cells identified protein phosphatase 2 (PP2A) complex subunits as ATRi response genes. In OCCC, PPP2R1A missense mutations cause amino acid substitutions at residue p.R183. Characterisation of a cohort of OCCC primary tumours revealed a higher prevalence of structural subunit (PPP2R1A) mutations than previously reported (50%) which frequently co-occurred with ARID1A mutations. ARID1A-mutant OCCC cells with heterozygous PPP2R1A p.R183P or p.R183W mutations displayed enhanced ATRi sensitivity in vitro and in vivo. The most profound cell-cycle defect caused by PPP2R1A missense mutation was an ATRi-induced reduction in active S phase. ATRi exposure in PPP2R1A mutants increased 53BP1 bodies, a mark of residual DNA damage in mitosis. Phospho-proteomic profiling of PPP2R1A mutant OCCC cells revealed the selective increase in phosphorylation of Lysine Deficient Protein Kinase 1 (WNK1) following ATRi exposure, as well as increased phosphorylation of the WNK1 substrate Oxidative Stress Response Kinase 1 (OSR1). Depletion of WNK1 rescued ATRi sensitivity and S phase defects in PPP2R1A mutant cells suggesting a novel role for this kinase.

Conclusions

The ability of PPP2R1A missense mutations to enhance ATRi sensitivity in tumours cells with pre-existing ARID1A mutations suggests that the co-occurrence of these mutations may be better predictors of ATRi sensitivity than either mutation alone. Increased phosphorylation of WNK1 may drive ATRi sensitivity in PPP2R1A mutant cells.

Legal entity responsible for the study

The authors.

Funding

Cancer Research UK.

Disclosure

S. Banerjee: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Genmabs; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Merck Sereno; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Oxcerna; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Shattuk Labs; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Immunogen; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Mersana; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche. C. Lord: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: KGaG; Financial Interests, Institutional, Research Grant: Artios; Financial Interests, Personal, Advisory Board: Syncona; Financial Interests, Personal, Advisory Board: Sun Pharma; Financial Interests, Personal, Advisory Board: Gerson Lehrman; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Vertex; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Dark Blue Therapeutics; Financial Interests, Personal, Stocks/Shares: Tango; Financial Interests, Personal, Stocks/Shares: Ovibio; Financial Interests, Personal, Stocks/Shares: Enedra Tx; Financial Interests, Personal, Stocks/Shares: Hysplex; Financial Interests, Personal, Stocks/Shares: Tesselate. All other authors have declared no conflicts of interest.

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Poster Display session Poster Display session

39P - Longitudinal Increases in Albumin-Adjusted Serum Calcium Predict Ovarian Cancer

Presentation Number
39P
Lecture Time
15:25 - 15:30
Speakers
  • Gary Schwartz (Grand Forks, ND, ND, United States of America)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Screening methods for ovarian cancer are urgently needed. Previously, we showed that women who develop ovarian cancer show an increase in serum calcium and a decrease in serum albumin (Schwartz et al, 2020, Gynecol Oncol 2020:159:264-269). These changes could be useful in screening. We asked, prior to their diagnosis, are women with ovarian cancer more likely to show a positive slope in their in albumin-adjusted serum calcium (a-asc)?

Methods

This is a population-based case-control study based in Sioux Falls, SD. Cases were women with epithelial ovarian cancer. Controls are women without a diagnosis of cancer. Patients with a history of cancer and/or parathyroid disease were excluded. Data are from patients’ Comprehensive Metabolic Panels (CMPs). We calculated albumin-adjusted serum calcium (a-asc) and estimated regression equations of each woman’s a-asc from pre-diagnosis to diagnosis. Data were analyzed by multiple regression, ANCOVA and logistic regression.

Results

We studied 124 cases and 98 controls. Cases were significantly older than controls (64.7 12.9 SD, vs. 41.0 16.8 years). For controls, the first and last a-asc was 9.23 mg/dL, for a slope of 0. For cases, the first and last values of a-asc were 9.28 and 9.37 mg/dL, for a slope of 0.04 mg/dl per year (P<0.001). The probability of cancer for a 0.04 mg/dL/year increase in a-asc increased with age until age 70 and showed a significant dose-response. The Odd Ratio (OR) of ovarian cancer for a 65 yr old woman with a 0.06 mg/dL increase/year was ∼3.0; the OR for a 1 mg/dl increase/year was ∼10. This effect was also seen for early stage tumors and persisted after age-adjustment.

Conclusions

In health, serum calcium levels are tightly regulated and the “expected” slope of a-asc is zero. A significant positive slope of a-asc in women with ovarian cancer, if confirmed by future studies, suggests that an increase in the slope a-asc could help identify women with undiagnosed ovarian cancer. Increases in a-asc were often small and could be easily overlooked. However, a computer algorithm could calculate the slope from patients’ annual records. Women with rising a-asc could be candidates for increased medical surveillance (e.g., transvaginal ultrasonography).

Legal entity responsible for the study

The authors.

Funding

This research was funded by grants from the University of North Dakota School of Medicine & Health Sciences, the Great Plains IDeA-CTR and the Coverys Community HealthCare Foundation (to GGS).

Disclosure

All authors have declared no conflicts of interest.

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Managing the consequences of cancer treatments Clinical case session

Management of immunotherapy and targeted therapies-induced toxicities

Lecture Time
14:55 - 15:15
Speakers
  • Antonio Jose Gonzalez Martin (Madrid, Spain)
Room
Auditorium 1A
Date
Sat, 18.06.2022
Time
14:15 - 15:45
Eisai - Recent advances in the management of endometrial cancer and their impact on the clinical practice Industry satellite symposium

Recent advances in the management of endometrial cancer

Lecture Time
18:05 - 18:25
Speakers
  • Ana Oaknin (Barcelona, Spain)
Room
Auditorium 1A
Date
Fri, 17.06.2022
Time
18:00 - 19:00
Poster Display session Poster Display session

30P - Molecular biomarkers by next generation sequencing predicting oncological outcomes in ovarian cancer patients

Presentation Number
30P
Lecture Time
14:40 - 14:45
Speakers
  • Shira Peleg Hasson (Tel Aviv, Israel)
Session Name
Room
Exhibition area
Date
Fri, 17.06.2022
Time
12:15 - 13:00

Abstract

Background

Ovarian cancer (OC) is the most common cause of gynecologic cancer mortality worldwide. Next generation sequencing (NGS) provides molecular biomarkers which can potentially predict oncological outcomes. We performed a retrospective study to examine progonostic biomarkes for ovarian cancer patients treated in our institution.

Methods

We retrospectively evaluated demographic and clinical information of OC patients referred for NGS molecular testing between 2011-2020 at the Tel-Aviv Medical Center. Cox models were used to analyze the clinical impact of molecular biomarkers including LOH and TMB by assessing overall survival (OS) and progression free survival (PFS).

Results

Of 1026 consecutive patients reviewed, 946 were included in the analysis: 108 (11.4%) were referred to NGS and 838 (88.6%) served as control. Patient baseline parameters were similar between the groups. High loss of heterozygosity (LOH) was associated with longer mOS (99.0 vs. 48.2 months, p=0.004). Sixty-six patients had information on TMB status: 75.8% (50/66) had low TMB status (<5) and 24.2% (16/66) had intermediate TMB status (5-15). None had a high TMB status. Analysis of TMB using the Breslow test showed that patients with TMB ≥4 had a statistically significant longer OS compared with patients with TMB<4 (92.8 months [95%CI, 47.1-138.6] vs. 52.77 months [95% CI, 26.4-79.2], p=0.026).

Conclusions

We identified LOH and TMB ≥4 as strong prognostic biomarkers among OC patients. Prospective studies evaluating larger cohorts are necessary to generate a more extensive evaluation of additional prognostic and predictive biomarkers.

Legal entity responsible for the study

The authors.

Funding

Roche Israel.

Disclosure

All authors have declared no conflicts of interest.

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Mini Oral session Abstract session

20MO - Time to deterioration in quality of life in patients (pts) with advanced endometrial cancer (aEC) treated with lenvatinib plus pembrolizumab (L+P) or treatment of physician’s choice (TPC)

Presentation Number
20MO
Lecture Time
13:00 - 13:05
Speakers
  • Domenica Lorusso (Rome, Italy)
Session Name
Room
Auditorium 1A
Date
Sat, 18.06.2022
Time
13:00 - 14:00

Abstract

Background

In study 309/KEYNOTE-775, L+P showed significant OS and PFS benefits and improved ORR vs TPC in pts with aEC following prior platinum-based therapy. There were no substantial differences in health-related quality of life (HRQoL) scores between the 2 arms at 12 weeks. We describe a post-hoc analysis of time to first (TTfD) and time to definitive (TTdD) deterioration (by 10 points) of patient-reported outcomes (PROs).

Methods

Pts were randomized 1:1 to lenvatinib 20 mg QD PO + pembrolizumab 200 mg IV Q3W (n=411) or TPC (n=416; doxorubicin 60 mg/m2 IV Q3W or paclitaxel 80 mg/m2 IV QW, 3 wks on/1 wk off). PROs were assessed on day 1 of each treatment cycle (L+P and doxorubicin, 21 days; paclitaxel, 28 days) until the end of treatment visit using EORTC QLQ-C30, QLQ-EN24, and EQ-5D-5L in pts with ≥1 study dose and ≥1 postbaseline PRO. TTfD for the EORTC QLQ-C30 and QLQ-EN24 was defined as the time from treatment start to first onset of a ≥10-point increase (symptom score) or decrease (functional/global health status [GHS] score) from baseline. TTdD was defined as the time from treatment start to first onset of an increase (symptom score) or decrease (functional/GHS score) of ≥10 points from baseline without subsequent recovery.

Results

The mean observation period for PRO measures was longer for L+P vs TPC (eg, EORTC QLQ-C30: L+P, 9.3 mos; TPC, 4.3 mos). TTfD was generally similar between the 2 arms for most functional scales. Among the symptom scales, TTfD for dyspnea, poor body image, tingling/numbness, and hair loss favored L+P over TPC, whereas pain, appetite loss, diarrhea, and muscular pain favored TPC. TTdD favored L+P for most of the assessed scales.

Conclusions

Although TTfD did not demonstrably favor either arm, L+P was favored over TPC for almost all scales in the TTdD analysis. This may be due to longer follow-up and/or overall greater efficacy with L+P vs TPC. These data along with previously reported positive efficacy, safety, and overall HRQoL scores from Study 309/KEYNOTE-775 further support L+P for use in pts with aEC following prior platinum-based therapy.

Clinical trial identification

NCT03517449.

Editorial acknowledgement

Medical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: MSD; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: Clovis Oncology; Financial Interests, Personal, Other, Consultancy: PharmaMar; Financial Interests, Personal, Other, Consultancy: Amgen; Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Clovis Oncology; Financial Interests, Personal, Other, Consultancy: GSK; Financial Interests, Personal, Other, Consultancy: MSD; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Other, Consultancy: Immunogen; Financial Interests, Personal, Other, Consultancy: Genmab; Financial Interests, Personal, Other, Consultancy: Seagen; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Seagen; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Immunogen; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Genmab; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Oncoinvest; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Corcept; Financial Interests, Personal, Advisory Board, Invited Member of Advisory Board: Sutro; Financial Interests, Institutional, Funding, Grant for Founding Academic Trial: MSD; Financial Interests, Institutional, Funding, Grant for Founding Academic Trial: Clovis Oncology; Financial Interests, Institutional, Funding, Grant for Founding Academic Trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT Trial with Institutional Support for Coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT Trial with Institutional Support for Coordination: Genmab; Financial Interests, Institutional, Funding, Grant for founding academic trial: PharmaMar; Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca; Financial Interests, Institutional, Funding, Clinical trial/contracted research: Clovis Oncology; Financial Interests, Institutional, Funding, Clinical trial/contracted research: GSK; Financial Interests, Institutional, Funding, Clinical trial/contracted research: MSD; Financial Interests, Institutional, Funding, Clinical trial/contracted research: Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Immunogen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Incyte; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Novartis; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Roche; Financial Interests, Institutional, Invited Speaker, ENGOT Trial with Institutional Support for Coordination: MSD; Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: Genmab; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: Immunogen; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: Clovis; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: Incyte; Non-Financial Interests, Personal, Member, Board of Directors: GCIG. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche; Financial Interests, Personal, Advisory Board, Various: PharmaMar; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca; Financial Interests, Personal, Advisory Board, Various: AstraZeneca; Financial Interests, Personal, Advisory Board, Various: MSD/Merck; Financial Interests, Personal, Advisory Board, Various: Clovis Oncology; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: Tesaro; Financial Interests, Personal, Advisory Board, Various: Tesaro; Financial Interests, Personal, Advisory Board, Various: GSK; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Various: Pfizer; Financial Interests, Personal, Advisory Board, Various: Takeda; Financial Interests, Personal, Advisory Board, Various: BIOCAD; Financial Interests, Personal, Advisory Board, Various: Immunogen; Financial Interests, Personal, Advisory Board, Various: Mersana; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Personal, Advisory Board, Advisory role: Pieris; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Personal, Other, Steering Committee Member Clinical Guidelines: ESMO; Non-Financial Interests, Personal, Leadership Role, Chair, Scientific Committee: ACTO (Alleanza Contro il Tumore Ovarico). A. Casado Herraez: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: PharmaMar; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Tesaro; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Lilly; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: PharmaMar; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Roche. A.D. Santin: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Institutional, Funding: Tesaro; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Gilead Sciences; Financial Interests, Institutional, Funding: Puma Biotechnology; Financial Interests, Institutional, Funding: Genentech/Roche; Financial Interests, Institutional, Funding: R-Pharm; Financial Interests, Institutional, Funding: Immunomedics. E. Colomba: Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: Ipsen; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Travel. Accommodations, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Ipsen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer. D.S. Miller: Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Other, Honoraria: Clovis Oncology; Financial Interests, Personal, Member, Honoraria: Genentech; Financial Interests, Personal, Research Grant: EMD Serono Research & Development Institute; Financial Interests, Institutional, Research Grant: US Biotest; Financial Interests, Institutional, Research Grant: Advenchen Laboratories; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Xenetic Biosciences; Financial Interests, Institutional, Research Grant: Advaxis; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Aeterna Zentaris; Financial Interests, Institutional, Research Grant: TRACON Pharma; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Immunogen; Financial Interests, Institutional, Research Grant: Mateon Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Millennium Pharmaceuticas; Financial Interests, Institutional, Research Grant: Aprea AB; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: NVision; Financial Interests, Institutional, Research Grant: Leap Therapeutics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Syros Pharmaceuticals; Financial Interests, Institutional, Research Grant: Karyopharm Therapeutics; Financial Interests, Institutional, Research Grant: Agenus and Akesobio; Financial Interests, Institutional, Research Grant: Merck Sharpe & Dohme; Financial Interests, Personal, Other, Consulting Fees: Genentech; Financial Interests, Personal, Other, Consulting Fees: Tesaro; Financial Interests, Personal, Other, Consulting Fees: Eisai; Financial Interests, Personal, Other, Consulting Fees: AstraZeneca; Financial Interests, Personal, Other, Consulting Fees: Guardant Health; Financial Interests, Personal, Other, Consulting Fees: Janssen Oncology; Financial Interests, Personal, Other, Consulting Fees: Alexion Pharmaceuticals; Financial Interests, Personal, Other, Consulting Fees: Karyopharm Therapeutics; Financial Interests, Personal, Other, Consulting Fees: Incyte; Financial Interests, Personal, Other, Consulting Fees: Guardant Health; Financial Interests, Personal, Other, Consulting Fees: Janssen; Financial Interests, Personal, Other, Consulting Fees: Clovis Oncology; Financial Interests, Personal, Other, Consulting Fees: Asymmetrics Therapeutics LLC; Financial Interests, Personal, Other, Consulting Fees: Boston Biomedical Research Institute; Financial Interests, Personal, Other, Consulting Fees: Tarveda Therapeutics; Financial Interests, Personal, Other, Consulting Fees: Myriad Genetic Laboratories Inc.; Financial Interests, Personal, Other, Consulting Fees: GlaxoSmithKline LLC; Financial Interests, Personal, Other, Consulting Fees: AbbVie Inc.; Financial Interests, Personal, Other, Consulting Fees: EMD Serono Inc.; Financial Interests, Personal, Other, Consulting Fees: Seager Inc.; Financial Interests, Institutional, Other, Consulting Fees: Merck Sharpe & Dohme. K. Fujiwara: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Personal, Advisory Board: Nano Carrier; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Funding: Regenerone; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: Zeria; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Personal, Invited Speaker: Regenerone; Financial Interests, Personal, Invited Speaker: Zeria; Non-Financial Interests, Personal, Leadership Role: GOTIC. S. Pignata: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AZ; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: PPharmaMar; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: MSD; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Az. S.E. Baron-Hay: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Merck Sharpe & Dohme; Financial Interests, Personal, Advisory Role: Novartis. I.L. Ray-Coquard: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Mersana; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Institutional, Other, COLIBRI Translational Research: BMS; Financial Interests, Personal, Advisory Board: Oxnea; Financial Interests, Personal, Advisory Board: Merck Sereno; Financial Interests, Personal, Advisory Board: Agenus; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Macrogenics; Financial Interests, Institutional, Advisory Board, translational research NEOPREMBROV trial: MSD; Financial Interests, Personal, Advisory Board: Clovis; Non-Financial Interests, Personal, Principal Investigator: PAOLA1. R. Shapira-Frommer: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Medison; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Neopharm; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, consultation: Msdison; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD. R. Massaad: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. A. Martin Nguyen: Financial Interests, Personal and Institutional, Stocks/Shares: Merck & Co., Inc.; Financial Interests, Personal and Institutional, Full or part-time Employment: Merck & Co., Inc. Q. Zhao: Financial Interests, Personal and Institutional, Full or part-time Employment: Eisai Inc. J. McKenzie: Financial Interests, Personal and Institutional, Full or part-time Employment: Eisai Inc. V.S. Prabhu: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal and Institutional, Stocks/Shares: Merck & Co., Inc.; Financial Interests, Personal and Institutional, Other, Travel, Accommodations, Expenses: Merck & Co., Inc. V. Makker: Financial Interests, Institutional, Funding, Study funding: Merck; Financial Interests, Institutional, Funding, Study funding: Eisai; Financial Interests, Institutional, Funding, Study funding: Clovis; Financial Interests, Institutional, Funding, Study funding: Karyopharm; Financial Interests, Institutional, Funding, Study funding: AstraZeneca; Financial Interests, Institutional, Funding, Study support: Zymeworks; Non-Financial Interests, Personal, Principal Investigator: Merck; Non-Financial Interests, Personal, Advisory Role: Eisai; Non-Financial Interests, Personal, Advisory Role: Clovis; Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: GSK; Non-Financial Interests, Personal, Advisory Role: Karyopharm; Non-Financial Interests, Personal, Advisory Role: Iteos; Non-Financial Interests, Personal, Advisory Role: Faeth. All other authors have declared no conflicts of interest.

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