Neutrophil-to-lymphocyte ratio predicts platinum sensitivity in epithelial ovarian cancer patients: A MITO24 retrospective study

abstracts Tesaro, AstraZeneca, Pfizer, Clovis; Travel / Accommodation / Expenses: Roche, Novartis, Tesaro, Pfizer. S. Wang: Full / Part-time employment: Tesaro. All other authors have declared no conflicts of interest.

1018P

Tumour-infiltrating lymphocytes (TILs) in patients with epithelial ovarian cancer undergoing neoadjuvant chemotherapy: A retrospective study

Background: The role of the adaptive immune response in tumors has been widely explored.TILs are related with a better survival in several tumors. In ephitelial ovarian cancer (EOC) there are few data focusing on the effects of neoadjuvant chemotherapy (NACT) on T-cell infiltration, with controversial results.TILs may represent a prognostic and predictive biomarker and may have a role in selecting patients for immunotherapy. Methods: We retrospectively evaluated 131 patients with stage IIIC-IV EOC who received NACT with platinum and taxane, interval debulking surgery (IDS) and chemotherapy post IDS.14 patients were excluded due to complete response. Stromal and Intratumoral TILs (sTILs-iTILs) were evaluated in tumor biopsies (pre NACT samples) and on residual disease post surgery (post NACT samples), using the criteria defined by the International TILs Working Group. The objective of the study was evaluating whether NACT could determine an increase T-cell infiltration with a consequent positive effect on outcome. Results: Median follow up was 70.25 months.OS at 2 and 5 years were 68.6% (95%CI: 61.0%-77.1%) and 26.8% (95%CI:19.5%-36.8%) respectively.In the final analysis 50 patients were excluded due to the lack of suitable pre NACT samples.There was no association between sTILS or iTILs values assessed on pre and/or post NACT samples with OS (HR ¼ 0.99; HR ¼ 1.01 respectively) and PFS (HR ¼ 0.99; HR ¼ 1.002 respectively). However, investigating the difference of sTILs between post (median 12; IQR 6-20) and pre NACT samples (median 7; IQR 3.25-17), we found that an increase in sTILs in post NACT compared to pre NACT samples was associated with reduced mortality risk (HR ¼ 0.71; 95% CI: 0.50-1.00 p ¼ 0.05).Furthermore a no-linear association between the difference between post and preNACT iTILs and OS was detected (p ¼ 0.11). Conclusions: These findings, although limited by the small sample size and the retrospective nature of this analysis, suggest a possible role of TILs detected in residual tumor after NACT as prognostic biomarker in EOC. Further data are needed in order to confirm the role of TILs after NACT and their possible relevance to predict efficacy of immunotherapeutic strategies in this setting. Legal entity responsible for the study: Nicoletta Colombo, Sara Giovannoni. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

1019P

Prognostic significance of elements of the adaptive immunity in the microenvironment of epithelial ovarian cancer

P. Foukas, G-A. Koliou, A. Papoudou-Bai, A. Charchanti, E. Vrettou, C. Poulios, K. Chatzopoulos, V. Kotoula, E. Fountzilas, R. Zakopoulou, A. Visvikis, G. Pentheroudakis, D.G. Pectasides, G. Aravantinos, G. Oikonomopoulos, A. Papanikolaou, D. Haidopoulos, F. Zagouri, G. Fountzilas, A. Goussia 1 Data Office, Hellenic Cooperative Oncology Group (HeCOG), Athens, Greece Background: The characterization of the adaptive immune landscape in epithelial ovarian cancer (EOC) is of paramount importance for the stratification of patients (pts) for therapeutic interventions, especially in the context of immunotherapy. Methods: In the present analysis pts with EOC and available tumor tissue were included. All pts had received treatment with platinum and paclitaxel.We evaluated elements of the adaptive immunity such as Tertiary Lymphoid Structures (TLS), plasma cells (PCs) and CD8þT cells, intraepithelial (iCD8) and stromal (sCD8), as well as p53 immunoexpression. Assessment of TLS (presence, absence) and PCs (4-tiered score) was performed in H&E stained whole tumor sections whereas of CD8 and p53 in IHC stained Tissue Microarrays (TMAs), constructed from the same tumor area. For iCD8, 5 cells/HPF was considered as the cut-off value for low vs high expression, whereas absolute absence of p53 expression or immunopositivity in > 60% of tumor cells was considered as p53 mutated by IHC (mIHCp53). Survival data have been retrieved from 613 patients.

v416 | Gynaecological Cancers

Results: From 04/1996 to 11/2016 687 pts were treated; median age was 58.8 years (range 21.7-84.4). Stage III disease was diagnosed in 431 (69.3%), while stage IV in 70 (11.3%) pts. Most tumors had absence of TLS (74.2%), 0-1 PCs score (78.7%), low iCD8 and sCD8 expression (75.4% and 50.3%) and mIHCp53 (73.6%). The presence of TLS correlated with high iCD8 and sCD8 expression and 2-3 PCs score (all p’s <0.001), but not with prognosis in this cohort (p ¼ 0.99). The median OS was 71.9 months (95% CI 65.5-83.9). Age was an independent unfavorable prognosticator for OS (HR ¼ 1.02, p < 0.001). Low iCD8 expression and mIHCp53 univariately conferred higher risk of death (HR ¼ 1.42; p ¼ 0.038 and HR ¼ 1.54; p ¼ 0.010, respectively). Upon multivariate analysis, low iCD8 expression retained its unfavorable prognostic significance for OS (HR ¼ 1.54, p ¼ 0.011), while a trend towards worse survival was detected for mIHCp53 (HR ¼ 1.38, p ¼ 0.062). Conclusions: The presence of effector cells of adaptive immunity such as PCs and cytotoxic T cells correlated with the presence of TLS and was closely linked to clinical outcome in EOC. Legal entity responsible for the study: Hellenic Cooperative Oncology Group (HeCOG). Funding: Hellenic Cooperative Oncology Group (HeCOG). Disclosure: E. Fountzilas: Shareholder / Stockholder / Stock options: Deciphera; Travel / Accommodation / Expenses: K.A.M Oncology / Hematology; Travel / Accommodation / Expenses: Merck. G. Pentheroudakis: Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Merck; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Roche; Advisory / Consultancy, Leadership role: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy, Leadership role, Research grant / Funding (institution): Lilly; Leadership role, Research grant / Funding (institution): Boehringer; Leadership role: Enorasis. G. Aravantinos: Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche Hellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Genesis Pharma; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer. G. Fountzilas: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche; Honoraria (self): AstraZeneca. All other authors have declared no conflicts of interest.

1020P

Neutrophil-to-lymphocyte ratio predicts platinum sensitivity in epithelial ovarian cancer patients: A MITO24 retrospective study

A. Farolfi1, E. Scarpi2, F. Greco3, A. Bergamini4, L. Longo5, S. Pignata6, C. Casanova7, V. Del Vecchio8, A. Bologna9, M. Orditura10, L. Zavallone11, J. Ventriglia6, V. Galla2, E. Franzese12, E. Pigozzi3, V. Loizzi8, G. Giorda13, D. Giardina5, R. Cioffi4, U. De Giorgi1 1 Medical Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Srl - IRCCS, Meldola, Italy, 2Unit of Biostatistics and Clinical Trials, Istituto Tumori della Romagna I.R.S.T., Meldola, Italy, 3Medical Oncology Unit, ULSS 9 Regione Veneto, Legnago, Italy, 4Department of Obstetrics and Gynaecology, San Raffaele Scientific Institute, Milan, Italy, 5Medical Oncology Unit, Ramazzini Hospital, Carpi, Italy, 6 Urology and Gynecology, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, Naples, Italy, 7Department of Medical Oncology, Santa Maria delle Croci Hospital, a degli Studi di Bari & IRCCS Ravenna, Italy, 8Gynecology Oncology Unit, Universit Istituto Oncologico Giovanni Paolo II, Bari, Italy, 9Medical Oncology Unit, IRCCS– 10 Arcispedale S. Maria Nuova, Reggio Emilia, Italy, Department of Clinical and Experimental Medicine "F. Magrassi", Universit a degli Studi della Campania "Luigi Vanvitelli", Caserta, Italy, 11Department Medical Oncology, Infermi Hospital, Ponderano, 12 a degli Italy, Department of Clinical and Experimental Medicine "F. Magrassi", Universit Studi della Campania Luigi Vanvitelli, Naples, Italy, 13Department of Gynecological Oncology, Centro di Riferimento Oncologico (CRO) IRCCS, Aviano, Italy Background: The prognostic value of the inflammatory indexes (eg. neutrophil-tolymphocyte ratio, NLR; and systemic immune-inflammation index, SII) was demonstrated among patients with epithelial ovarian cancer (EOC). This study aimed to evaluate their predictive value in terms of platinum-free interval (PFI) as regard to bevacizumab treatment received. Methods: A total of 375 EOC patients were retrospectively analyzed, 301 treated with chemotherapy alone and 74 with bevacizumab, with the decision to include this drug in the chemotherapy regimen left to the discretion of the treating physician. The correlation between NLR (defined as the ratio of neutrophil to lymphocyte count) and SII, calculated as (platelet count  neutrophil count)/lymphocyte count, and PFI were analyzed using logistic regression analyses adjusted for baseline patient characteristics. Cutoff values were determined using Receiver Operating Characteristic (ROC) analysis. Results: In univariate analysis, patients with high NLR (3) and SII (730) had a significantly shorter PFI at 6 and 12 months in overall cohort. In multivariate analysis, only NLR was an independent predictive factor for PFI at 6 months (OR ¼ 2.52, 95% CI 1.30–4.87, p ¼ 0.006) and at 12 months (OR ¼ 2.05, 95% CI 1.05–4.01, p ¼ 0.036) in the overall population and in the chemotherapy group (OR ¼ 2.77, 95% CI 1.38–5.56, p ¼ 0.004; HR ¼ 2.27, 95% CI 1.10–4.70, p ¼ 0.027, respectively). Inflammatory indexes were not predictive for PFI in the bevacizumab group (Table).

Volume 30 | Supplement 5 | October 2019

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S. Giovannoni1, A. Garbi1, G. Parma1, M. Lapresa1, E. Zaccarelli1, A. Vingiani2, I. Ardoino3, G. Pruneri4, N. Colombo1 1 Gynaecological Oncology, IEO- Istituto Europeo di Oncologia, Milan, Italy, 2Pathology, IEO- Istituto Europeo di Oncologia, Milan, Italy, 3Statistics; Clinical Sciences and Community Helath, University of Milan, Milan, Italy, 4Pathology, INT Istituto Nazionale Tumori, Milan, Italy

Annals of Oncology

abstracts

Annals of Oncology

Table: 1020P PFI at 6 months

PFI at 12 months

N. pts

OR (95% CI)

p

NLR <3 3

74 80

139 68

1.00 2.52 (1.30-4.87)

SII <730 730

52 102

99 108

CT NLR <3 3

62 69

SII <730 730 CTþB NLR <3 3 SII <730 730

N. pts

N. pts

OR (95% CI)

p

0.006

113 106

98 37

1.00 2.05 (1.05-4.01)

0.036

1.00 0.74 (0.36-1.53)

0.413

76 143

73 62

1.00 0.91 (0.45-1.84)

0.786

115 48

1.00 2.77 (1.38-5.56)

0.004

98 89

78 24

1.00 2.27 (1.10-4.70)

0.027

41 90

80 83

1.00 0.76 (0.35-1.67)

0.498

63 124

56 46

1.00 0.84 (0.39-1.82)

0.663

12 11

24 20

1.00 0.47 (0.04-5.15)

0.538

15 17

20 13

1.00 0.75 (0.11-5.25)

0.774

1.00 1.65 (0.13-20.56)

0.696

1.00 1.78 (0.21-15.14)

0.599

11 12

19 25

13 19

17 16

1022P

Conclusions: The NLR was an independent predictive factor for platinum-sensitivity in patients with EOC treated with chemotherapy. Its predictive role seems to be lost in patients treated with bevacizumab. Legal entity responsible for the study: MITO group. Funding: MITO group. Disclosure: All authors have declared no conflicts of interest.

1021P

The prognostic impact of monocyte to lymphocyte ratio (MLR) in advanced epithelial ovarian cancer (EOC)

M. Cucurull Salamero1, I. Teruel Garcıa2, A.J. Arroyo3, B. Pardo3, M. Gil3, J.M. Piulats4, H. Pla5, C. Fina5, M.P. Barretina Ginesta6, L. Angelats1, E. Felip Falgas2, C. Erasun Lecuona7, J.J. Garcıa Mosquera8, S. Martinez Roman9, E. Carballas10, J. Hernandez11, A. Esteve11, M. Romeo1 1 Medical Oncology, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, Badalona, Spain, 2Medical Oncology, Institut Catala d’Oncologia (ICO), a d’Oncologia, L’Hospitalet, Barcelona, Spain, 3Medical Oncology, Institut Catal Barcelona, Spain, 4Department of Medical Oncology, Genitourinary, Melanoma and Sarcoma Unit, Institut Catal a d’Oncologia-IDIBELL-CIBERONC, Barcelona, Spain, 5 Medical Oncology, Institut Catal a d’Oncologia, Girona, Spain, 6Department Medical Oncology, ICO - Institut Catal a d’Oncologia Girona (Hospital Universitari Josep Trueta Hospital Universitari Josep Trueta), Girona, Spain, 7Oncology Medical, Hospital Universitario Germans Trias i Pujol, Badalona, Spain, 8Medical Oncology, Hospital Dexeus - Instituto Oncologico Rosell, Barcelona, Spain, 9Gynecology Department, Hospital Germans Trias I Pujol, Badalona, Spain, 10Oncology Medical, Hospital Universitario Germans Trias i Pujol, Badalona, Spain, 11Cancer Statitics Department, Hospital-based Cancer Registry, Institut Catal a d’Oncologia Badalona, Badalona, Spain Background: Among the inflammation-related biomarkers, high MLR values are associated to poorer outcomes in different cancers. We explored the prognostic role of MLR in a multicenter series of EOC patients (p). Methods: We included all pathologically confirmed stage III/IV EOC p who had undergone radical treatment in Institut Catala d’Oncologia (ICO) Badalona (from 2008 to 2017), ICO Girona (2013 - 2015) and ICO Hospitalet (2011-2014). MLR was calculated from the counts of monocytes and lymphocytes at diagnosis. Overall survival (OS) was assessed by Kaplan Meyer. The impact of MLR on OS was explored by COX regression. Variables included in these analyses were: histology (high grade serous carcinomas –

Volume 30 | Supplement 5 | October 2019

Expenses: Roche. M. Gil: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche Pharma; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: PharmaMar. E. Felip Falgas: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Kyowa Kirin; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Roche. C. Erasun Lecuona: Full / Part-time employment: Pierre Fabre. J.J. Garcıa Mosquera: Honoraria (self), Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Otsuka; Travel / Accommodation / Expenses: Mundipharma. S. Martinez Roman: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche Pharma. All other authors have declared no conflicts of interest.

TP53 hotspot mutations as immunoreactive neoantigens define a signature with differential survival outcomes in advanced ovarian cancer

M. Garziera1, E. Cecchin1, J. Polesel2, V. Canzonieri3, R. Sorio4, S. Gagno1, S. Scalone5, R. Roncato1, E. De Mattia1, E. Poletto6, G. Giorda7 1 Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy, 2Unit of Cancer Epidemiology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy, 3Pathology Unit, Centro di Riferimento Oncologico (CRO), Aviano, Italy, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy, 4Department of Medical Oncology, Centro di Riferimento Oncologico CRO, Aviano, Italy, 5Department of Medical Oncology, Centro di Riferimento Oncologico - CRO, Aviano, Italy, 6Department of Oncology, Azienda Sanitaria Universitaria Integrata di Udine - Ospedale Santa Maria della Misericordia, Udine, Italy, 7 Gynaecological Oncology Unit, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy Background: Hotspot mutations (HSM) in TP53 (R175, Y220, G245; R248, R273) have been recognized as potential immunoreactive neoantigens able to achieve intratumoral T cell responses in advanced ovarian cancer, particularly in high-grade serous ovarian cancer (HGSOC). The purpose of this study was to assess if HSM, Non-HSM (missense non-HSM) and Other (INDELs, stop gained, splice site) somatic mutations in TP53, confer differential survival outcomes. Presence of circulating p53-autoantibodies (p53-AAbs) was also tested and correlated with TP53 mutation spectra. Methods: A series of 83 patients (71 HGSOC) with advanced (III-IV stage, G2-3) ovarian cancer, treated with primary debulking surgery and platinum-based therapy, were retrospectively enrolled. Characterization of TP53 mutations in chemo-naı¨ve tumours was performed with a targeted next-generation sequencing approach. An ELISA kit was used to detect p53-AAbs. Platinum-free interval (PFI), progression-free survival (PFS) and Overall survival (OS) were compared using Kaplan-Meier, Log-rank test and Cox proportional hazard models (adjusted for age, stage, serous subtype, residual tumour). Results: Somatic mutations in TP53 were found in 74.7% of patients; among them, 71% was -p53-AAbs and 29% was þp53-AAbs. The repertoire of TP53 mutations was significantly different according to p53-AAbs (p ¼ 0.005), with prevalence of Other mutations (50%) in patients -p53-AAbs. In multivariate analysis (WT as the ref. category), patients with: i) Non-HSM mutations had reduced PFI (p ¼ 0.026), PFS (p ¼ 0.014) and OS (p ¼ 0.048); ii) Other mutations had reduced PFI (p ¼ 0.002) and PFS (p ¼ 0.007), but not OS (p ¼ 0.062); iii) HSM mutations were not associated with PFI (p ¼ 0.605), PFS (p ¼ 0.681) and OS (p ¼ 0.437). Conclusions: Molecular profile of chemo-naı¨ve tumours in advanced ovarian cancer showed different outcomes coupled to specific TP53 signatures. A more aggressive mutational profile in TP53 was observed in patients without p53-AAbs. Non-synonymous mutated neoantigens arised from tumour clones, appear to be critical to identify patients best suited to immunotherapy. Further investigations in the tumour microenvironment are needed to confirm these preliminary findings. Legal entity responsible for the study: Giorgio Giorda.

doi:10.1093/annonc/mdz250 | v417

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N. pts

HGSOC-, other), stage (III, IV), primary treatment (primary surgery –PS-, interval debulking surgery –IDS-), residual disease (R0 vs R1/R2), age at diagnosis and MLR (the last two assessed as continuous variables). Maximally selected rank statistics was used to identify an optimal MLR cut-off value that resulted in two groups with different OS, in the whole sample, in p who underwent PS, and in p who received IDS. Results: 128 p were included. Median age at diagnosis was 62 years; 82.9% were HGSOC; 65.8% were stage III; 52.3% had undergone PS, and 47.7% IDS; 73.4 % were R0. Stage III, R0, and low MLR values were associated to better OS (p ¼ 0.047, <0.0007, and 0.043, respectively) in the multivariate Cox analyses (analysis done in 109 p, as 19 observations deleted due to missingness). Optimal MLR cut-off was 0.33: 44 p were low risk (MLR-lo), and 84 p were high risk (MLR-hi), with significant differences in OS between them (82.36 vs 41.8 months, p ¼ 0.032). Among p who underwent PS (67p), optimal cut-off was 0.42: 46p MLR-lo, and 21p MLR-hi (OS: 87.17 vs 41.2 months, p ¼ 0.012). Among p who underwent IDS, an optimal cut-off related to OS could not be identified. Conclusions: High MLR values appear to be related to worse OS in EOC p, specifically among p who underwent PS, but not among p who received IDS. MLR could be used to identify high risk p, even undergoing PS, in whom alternative therapies may be explored. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: M. Cucurull Salamero: Speaker Bureau / Expert testimony, Travel / Accommodation /