- Email: [email protected]
Surrogate endpoint of progression-free (PFS) and overall survival (OS) for advanced ovarian cancer (AOC) patients (pts) treated with neo-adjuvant chemotherapy (NACT): Results of the CHIVA randomized phase II GINECO study
abstracts
Annals of Oncology
Celgene; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Ipsen; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self): Pierre Fabre; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Takeda; Research grant / Funding (self): AstraZeneca. All other authors have declared no conflicts of interest.
1016P
Surrogate endpoint of progression-free (PFS) and overall survival (OS) for advanced ovarian cancer (AOC) patients (pts) treated with neoadjuvant chemotherapy (NACT): Results of the CHIVA randomized phase II GINECO study 1
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F. Lecuru , E. Pujade-Lauraine , S. Hamizi , A. Caumont-Prim , N. Raban , E. Malaurie , P. Pautier7, M-C. Kaminsky-Forrett8, J. Meunier9, J. Alexandre10, D. Berton-Rigaud11, N. Dohollou12, C. Dubot13, A. Floquet14, L. Favier15, L. Venat-Bouvet16, M. Fabbro17, C. Louvet18, A. Lortholary19, G. Ferron20 1 Service de Cance´rologie, Hopital European George Pompidou, Paris, France, 2Medical Oncology, Clinical Research, ARCAGY-GINECO, Paris, France, 3Oncologie Me´dicale Pavillon 1F, Centre Hospitalier Lyon Sud, Pierre Be´nite, France, 4Biostatistique, Exystat, Malakoff, France, 5Poˆle Re´gional de Cance´rologie, Service d’Oncologie, Hoˆpital de la Mile´trie - CHU de Poitiers, Poitiers, France, 6Oncologie, Radiothe´rapie, CHI de Cre´teil, Cre´teil, France, 7Gyne´cologie Me´dicale, Gustave Roussy, Villejuif, France, 8Oncologie Me´dicale, ICL Institut de Cance´rologie de Lorraine, Vandoeuvre-les-Nancy, France, 9 Service d’Oncologie Me´dicale, Centre Hospitalier Re´gional d’Orle´ans, Orleans, France, 10 Unite´ d’Oncologie Me´dicale, Hoˆpital Cochin, Paris, France, 11Oncologie Me´dicale, ICO Institut de Cancerologie de l’Ouest Rene´ Gauducheau, Saint-Herblain, France, 12 Oncologie - Radiothe´rapie, Polyclinique Bordeaux Nord, Bordeaux, France, 13 Oncologie Me´dicale, Hoˆpital Rene´ Huguenin - Institut Curie, St. Cloud, France, 14 Oncologie Me´dicale, Institute Bergonie´, Bordeaux, France, 15Oncologie Me´dicale, Centre Georges Franc¸ois Leclerc, Dijon, France, 16Oncologie Me´dicale, Centre Hospitalier Universitaire Dupuytren, Limoges, France, 17Parc Euromedecine, Oncologie Me´dicale, ICM Val d’Aurelle, Montpellier, France, 18Service d’Oncologie, Institut Mutualiste Montsouris, Paris, France, 19Oncologie Me´dicale, Hoˆpital Prive´ du Confluent S.A.S., Nantes, France, 20De´partement de Chirurgie Oncologique, Institut Claudius Regaud, Toulouse, France Background: NACT is increasingly used as a model to explore new targeted therapy in combination with CT in AOC. Whether an intermediate endpoint could be used as surrogate of PFS and/or OS in pts treated with NACT remains currently elusive and was explored retrospectively in the CHIVA trial. Methods: Patients (pts) with FIGO stage IIIC-IV AOC considered as unresectable after laparoscopic (Lap) evaluation were treated with 3 to 4 cycles of platinum-taxane NACT þ oral nintedanib before interval debulking surgery (IDS). CT (up to 6 cycles in total) and nintedanib were pursued post-operatively. Were measured response rates at the end of NACT according to RECIST (ORR) with CT-scan and to GCIG with CA125, initial Peritoneal Cancer Index (PCI) and its evolution at IDS, complete surgical resection rate (CC0), pathologic complete or near complete response rate (pCR). These covariates in univariate analysis were included together with other prognostic clinical covariates:age, FIGO stage, ECOG, tumor size, ascitis, neutrophil/lymphocyte ratio, platelet and hemoglobin counts and symptoms (pain). Results: A total of 163/188 pts included in the CHIVA trial were evaluable for the analysis. Median follow-up is 42. 6 mos (95% CI: 39.9-44.8). In the univariate Cox model, ECOG, ascitis, neutrophil/lymphocyte ratio, PCI at baseline, RECIST ORR, CC0 at IDS, pCR and treatment arm were correlated (p < 0.05) to PFS and/or OS. In the multivariate Cox model, RECIST ORR (p < 0.01) and CC0 at IDS (p < 0.01) were the only
Volume 30 | Supplement 5 | October 2019
variables predictive of both PFS and OS. The median PFS was respectively 10.4, 15.1 and 18.3 mos among the 3 groups of pts with 1) No ORR and no CC0; 2)only CC0 or only ORR; 3)ORR and CC0. PFS Hazard Ratio was 0.33 [0.20; 0.52], 0.43 [0.32; 0.70] and 0.68 [0.44; 1.06] for group 3v1, 2vs1 and 2v3 respectively. Median OS was 25.4, 41.0 mos and not reached for group 1, 2, and 3 respectively (p < 0.001). Conclusions: Results from the CHIVA trial suggest that the rate of patients who achieve both a RECIST response to NACT and a complete surgical resection (CC0) at IDS could be used as the main primary endpoint for future NACT trials. Clinical trial identification: 2011-006288-23. Legal entity responsible for the study: ARCAGY-GINECO. Funding: Boehringer Ingelheim. Disclosure: F. Lecuru: Advisory / Consultancy, Board: AstraZeneca; Advisory / Consultancy, Proctoring: Intuitive Surgical. E. Pujade-Lauraine: Honoraria (self), Self: AstraZeneca; Honoraria (self), Self: Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Tesaro. N. Raban: Travel / Accommodation / Expenses: Roche. P. Pautier: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Genentech; Research grant / Funding (institution): PharmaMar; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Tesaro. J. Alexandre: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Novartis. N. Dohollou: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly. A. Floquet: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche. C. Louvet: Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Servier; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. G. Ferron: Honoraria (self): Olympus Europe; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.
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Immune-related gene expression profiling after neoadjuvant chemotherapy (NACT) of ovarian high-grade serous carcinoma
L.M. Manso1, I. Lodewijk2, E. Bernal Hertfelder1, C. Suarez-Cabrera2, J.L. Garcia3, nas5 S. Wang4, J.M. Paramio2, M. Due~ 1 Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain, 2Molecular Oncology, Centro de Investigaciones Energe´ticas, Medioambientales y Tecnol ogicas (CIEMAT), Madrid, Spain, 3Pathology Department, University Hospital 12 de Octubre, 4 5 Madrid, Spain, Tesaro Inc, Massachusetts, MA, USA, Molecular Oncology, University Hospital 12 de Octubre, Madrid, Spain Background: In patients with stage III or IV HGSOC who are not suitable for primary surgery (PDS), 3 cycles of platinum based NACT followed by interval surgery (IDS) and adjuvant chemotherapy is an accepted treatment approach. NACT enhances host immune response by increasing levels of PD1, CTLA4 and PDL1 (Bo¨hm S et al. Clin Cancer Res 2016). Gene expression profiling of tumors has identified prognostic signatures for patient selection with immunotherapy (Ribas A et al. J Clin Oncol 2015). Methods: The purpose of this study is to assess the effect of neoadjuvant chemotherapy (NACT) on immune activation in stage IIIC/IV tubo-ovarian high-grade serous carcinoma (HGSOC). We obtained pre- and post-treatment omental biopsies from a total of 45 patients undergoing platinum-based NACT followed by IDS. We measured T-cell density and phenotype, immune activation, and markers of cancer-related inflammation using IHC. Messenger RNA expression was analyzed on the nCounter system using the PanCancer IO360 Panel. Results: There was evidence of T-cell activation in omental biopsies after NACT. CD4þ T cells showed enhanced IFNgproduction and antitumor Th1 gene signatures were increased. T-cell activation correlated with therapeutic response to NACT. The CD8 T-cell and CD45RO memory cell density in the tumor microenvironment was unchanged after NACT, but biopsies after a good therapeutic response had significantly fewer FoxP3 þ (Treg) cells. Biopsies of good therapeutic responders also showed areduction in a Treg gene signature in post versus pre-NACT samples.Preliminary results according to gene expression of the immune compartment reveal that tumor infiltrating lymphocytes were more abundant in samples from patients showing a good response over those with no or incomplete response to NACT, as well as an increase in gene signatures associated with antigen presentation and Cytokine and Chemokine Signaling. When comparing the expression profiles between samples obtained before or after NACT in patients showing incomplete response,we obtained an expected decreased in cellular proliferation signature. Conclusions: NACT may promote an immune modulatory effect that could improve or favour the further use of specific immunotherapy in HGSOC patients. Legal entity responsible for the study: Fundaci on para la Investigaci on 12 de Octubre. Funding: Tesaro SL. Disclosure: L.M. Manso: Research grant / Funding (self): Tesaro; Advisory / Consultancy: Roche, Novartis, Tesaro, AstraZeneca, Pfizer, Clovis; Speaker Bureau / Expert testimony: Roche, Novartis,
doi:10.1093/annonc/mdz250 | v415
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz250.024/5577294 by guest on 24 October 2019
foster cancer dissemination, reducing the likelihood of surgical eradication. The aim of this study was to assess whether the presence of germline polymorphisms in genes involved in angiogenesis and immunity pathways was predictive of R0. Methods: A cohort of 230 patients with stage III-IV, high grade epithelial OC treated with debulking surgery and platinum-based therapy without bevacizumab, was retrospectively enrolled. A panel of 192 single nucleotide polymorphisms (SNPs) in 34 angiogenesis and immune system-related genes was analyzed with Illumina GoldenGate Genotyping Assay. Log-additive, dominant and recessive genetic models were evaluated using a multivariate logistic regression adjusted for type of surgery (i.e. primary or interval). False discovery rate (FDR) test<0.2 was used for multiple testing data correction. Results: Thirteen SNPs were significantly associated with RD. Among them, MMP3rs569444, TLR3-rs5743303 and VEGFA-rs2146323 passed the FDR filter. Patients carrying the variant alleles of MMP3-rs569444 (OR ¼ 2.52, 95%CI 1.42-4.47, p ¼ 0.0326) and VEGFA-rs2146323 (OR ¼ 1.83, 95%CI 1.21-2.75, p ¼ 0.0375) showed an increased risk of RD. Conversely, TLR3-rs5743303 carriers were more likely to achieve R0 (OR ¼ 0.43, 95%CI 0.27-0.7, p ¼ 0.0004). Conclusions: Angiogenesis and the immune-system competence are key players in OC growth and could influence the burden of RD. In our cohort, individual polymorphisms on angiogenesis (VEGFA), extracellular matrix degradation (MMP3) and innate immunity activation (TLR3) pathways were independent predictive factors of RD. These markers, whether validated, might underline the role of host genetics factors in predicting R0. Moreover, if VEGFA-rs2146323 variant carriers could benefit the most from bevacizumab appears as an intriguing question. Legal entity responsible for the study: Toffoli Giuseppe. Funding: Has not received any funding. Disclosure: F. Puglisi: Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy:
Annals of Oncology
Celgene; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Ipsen; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self): Pierre Fabre; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Takeda; Research grant / Funding (self): AstraZeneca. All other authors have declared no conflicts of interest.
1016P
Surrogate endpoint of progression-free (PFS) and overall survival (OS) for advanced ovarian cancer (AOC) patients (pts) treated with neoadjuvant chemotherapy (NACT): Results of the CHIVA randomized phase II GINECO study 1
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F. Lecuru , E. Pujade-Lauraine , S. Hamizi , A. Caumont-Prim , N. Raban , E. Malaurie , P. Pautier7, M-C. Kaminsky-Forrett8, J. Meunier9, J. Alexandre10, D. Berton-Rigaud11, N. Dohollou12, C. Dubot13, A. Floquet14, L. Favier15, L. Venat-Bouvet16, M. Fabbro17, C. Louvet18, A. Lortholary19, G. Ferron20 1 Service de Cance´rologie, Hopital European George Pompidou, Paris, France, 2Medical Oncology, Clinical Research, ARCAGY-GINECO, Paris, France, 3Oncologie Me´dicale Pavillon 1F, Centre Hospitalier Lyon Sud, Pierre Be´nite, France, 4Biostatistique, Exystat, Malakoff, France, 5Poˆle Re´gional de Cance´rologie, Service d’Oncologie, Hoˆpital de la Mile´trie - CHU de Poitiers, Poitiers, France, 6Oncologie, Radiothe´rapie, CHI de Cre´teil, Cre´teil, France, 7Gyne´cologie Me´dicale, Gustave Roussy, Villejuif, France, 8Oncologie Me´dicale, ICL Institut de Cance´rologie de Lorraine, Vandoeuvre-les-Nancy, France, 9 Service d’Oncologie Me´dicale, Centre Hospitalier Re´gional d’Orle´ans, Orleans, France, 10 Unite´ d’Oncologie Me´dicale, Hoˆpital Cochin, Paris, France, 11Oncologie Me´dicale, ICO Institut de Cancerologie de l’Ouest Rene´ Gauducheau, Saint-Herblain, France, 12 Oncologie - Radiothe´rapie, Polyclinique Bordeaux Nord, Bordeaux, France, 13 Oncologie Me´dicale, Hoˆpital Rene´ Huguenin - Institut Curie, St. Cloud, France, 14 Oncologie Me´dicale, Institute Bergonie´, Bordeaux, France, 15Oncologie Me´dicale, Centre Georges Franc¸ois Leclerc, Dijon, France, 16Oncologie Me´dicale, Centre Hospitalier Universitaire Dupuytren, Limoges, France, 17Parc Euromedecine, Oncologie Me´dicale, ICM Val d’Aurelle, Montpellier, France, 18Service d’Oncologie, Institut Mutualiste Montsouris, Paris, France, 19Oncologie Me´dicale, Hoˆpital Prive´ du Confluent S.A.S., Nantes, France, 20De´partement de Chirurgie Oncologique, Institut Claudius Regaud, Toulouse, France Background: NACT is increasingly used as a model to explore new targeted therapy in combination with CT in AOC. Whether an intermediate endpoint could be used as surrogate of PFS and/or OS in pts treated with NACT remains currently elusive and was explored retrospectively in the CHIVA trial. Methods: Patients (pts) with FIGO stage IIIC-IV AOC considered as unresectable after laparoscopic (Lap) evaluation were treated with 3 to 4 cycles of platinum-taxane NACT þ oral nintedanib before interval debulking surgery (IDS). CT (up to 6 cycles in total) and nintedanib were pursued post-operatively. Were measured response rates at the end of NACT according to RECIST (ORR) with CT-scan and to GCIG with CA125, initial Peritoneal Cancer Index (PCI) and its evolution at IDS, complete surgical resection rate (CC0), pathologic complete or near complete response rate (pCR). These covariates in univariate analysis were included together with other prognostic clinical covariates:age, FIGO stage, ECOG, tumor size, ascitis, neutrophil/lymphocyte ratio, platelet and hemoglobin counts and symptoms (pain). Results: A total of 163/188 pts included in the CHIVA trial were evaluable for the analysis. Median follow-up is 42. 6 mos (95% CI: 39.9-44.8). In the univariate Cox model, ECOG, ascitis, neutrophil/lymphocyte ratio, PCI at baseline, RECIST ORR, CC0 at IDS, pCR and treatment arm were correlated (p < 0.05) to PFS and/or OS. In the multivariate Cox model, RECIST ORR (p < 0.01) and CC0 at IDS (p < 0.01) were the only
Volume 30 | Supplement 5 | October 2019
variables predictive of both PFS and OS. The median PFS was respectively 10.4, 15.1 and 18.3 mos among the 3 groups of pts with 1) No ORR and no CC0; 2)only CC0 or only ORR; 3)ORR and CC0. PFS Hazard Ratio was 0.33 [0.20; 0.52], 0.43 [0.32; 0.70] and 0.68 [0.44; 1.06] for group 3v1, 2vs1 and 2v3 respectively. Median OS was 25.4, 41.0 mos and not reached for group 1, 2, and 3 respectively (p < 0.001). Conclusions: Results from the CHIVA trial suggest that the rate of patients who achieve both a RECIST response to NACT and a complete surgical resection (CC0) at IDS could be used as the main primary endpoint for future NACT trials. Clinical trial identification: 2011-006288-23. Legal entity responsible for the study: ARCAGY-GINECO. Funding: Boehringer Ingelheim. Disclosure: F. Lecuru: Advisory / Consultancy, Board: AstraZeneca; Advisory / Consultancy, Proctoring: Intuitive Surgical. E. Pujade-Lauraine: Honoraria (self), Self: AstraZeneca; Honoraria (self), Self: Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Tesaro. N. Raban: Travel / Accommodation / Expenses: Roche. P. Pautier: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Genentech; Research grant / Funding (institution): PharmaMar; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Tesaro. J. Alexandre: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Novartis. N. Dohollou: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly. A. Floquet: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche. C. Louvet: Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Servier; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. G. Ferron: Honoraria (self): Olympus Europe; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.
1017P
Immune-related gene expression profiling after neoadjuvant chemotherapy (NACT) of ovarian high-grade serous carcinoma
L.M. Manso1, I. Lodewijk2, E. Bernal Hertfelder1, C. Suarez-Cabrera2, J.L. Garcia3, nas5 S. Wang4, J.M. Paramio2, M. Due~ 1 Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain, 2Molecular Oncology, Centro de Investigaciones Energe´ticas, Medioambientales y Tecnol ogicas (CIEMAT), Madrid, Spain, 3Pathology Department, University Hospital 12 de Octubre, 4 5 Madrid, Spain, Tesaro Inc, Massachusetts, MA, USA, Molecular Oncology, University Hospital 12 de Octubre, Madrid, Spain Background: In patients with stage III or IV HGSOC who are not suitable for primary surgery (PDS), 3 cycles of platinum based NACT followed by interval surgery (IDS) and adjuvant chemotherapy is an accepted treatment approach. NACT enhances host immune response by increasing levels of PD1, CTLA4 and PDL1 (Bo¨hm S et al. Clin Cancer Res 2016). Gene expression profiling of tumors has identified prognostic signatures for patient selection with immunotherapy (Ribas A et al. J Clin Oncol 2015). Methods: The purpose of this study is to assess the effect of neoadjuvant chemotherapy (NACT) on immune activation in stage IIIC/IV tubo-ovarian high-grade serous carcinoma (HGSOC). We obtained pre- and post-treatment omental biopsies from a total of 45 patients undergoing platinum-based NACT followed by IDS. We measured T-cell density and phenotype, immune activation, and markers of cancer-related inflammation using IHC. Messenger RNA expression was analyzed on the nCounter system using the PanCancer IO360 Panel. Results: There was evidence of T-cell activation in omental biopsies after NACT. CD4þ T cells showed enhanced IFNgproduction and antitumor Th1 gene signatures were increased. T-cell activation correlated with therapeutic response to NACT. The CD8 T-cell and CD45RO memory cell density in the tumor microenvironment was unchanged after NACT, but biopsies after a good therapeutic response had significantly fewer FoxP3 þ (Treg) cells. Biopsies of good therapeutic responders also showed areduction in a Treg gene signature in post versus pre-NACT samples.Preliminary results according to gene expression of the immune compartment reveal that tumor infiltrating lymphocytes were more abundant in samples from patients showing a good response over those with no or incomplete response to NACT, as well as an increase in gene signatures associated with antigen presentation and Cytokine and Chemokine Signaling. When comparing the expression profiles between samples obtained before or after NACT in patients showing incomplete response,we obtained an expected decreased in cellular proliferation signature. Conclusions: NACT may promote an immune modulatory effect that could improve or favour the further use of specific immunotherapy in HGSOC patients. Legal entity responsible for the study: Fundaci on para la Investigaci on 12 de Octubre. Funding: Tesaro SL. Disclosure: L.M. Manso: Research grant / Funding (self): Tesaro; Advisory / Consultancy: Roche, Novartis, Tesaro, AstraZeneca, Pfizer, Clovis; Speaker Bureau / Expert testimony: Roche, Novartis,
doi:10.1093/annonc/mdz250 | v415
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foster cancer dissemination, reducing the likelihood of surgical eradication. The aim of this study was to assess whether the presence of germline polymorphisms in genes involved in angiogenesis and immunity pathways was predictive of R0. Methods: A cohort of 230 patients with stage III-IV, high grade epithelial OC treated with debulking surgery and platinum-based therapy without bevacizumab, was retrospectively enrolled. A panel of 192 single nucleotide polymorphisms (SNPs) in 34 angiogenesis and immune system-related genes was analyzed with Illumina GoldenGate Genotyping Assay. Log-additive, dominant and recessive genetic models were evaluated using a multivariate logistic regression adjusted for type of surgery (i.e. primary or interval). False discovery rate (FDR) test<0.2 was used for multiple testing data correction. Results: Thirteen SNPs were significantly associated with RD. Among them, MMP3rs569444, TLR3-rs5743303 and VEGFA-rs2146323 passed the FDR filter. Patients carrying the variant alleles of MMP3-rs569444 (OR ¼ 2.52, 95%CI 1.42-4.47, p ¼ 0.0326) and VEGFA-rs2146323 (OR ¼ 1.83, 95%CI 1.21-2.75, p ¼ 0.0375) showed an increased risk of RD. Conversely, TLR3-rs5743303 carriers were more likely to achieve R0 (OR ¼ 0.43, 95%CI 0.27-0.7, p ¼ 0.0004). Conclusions: Angiogenesis and the immune-system competence are key players in OC growth and could influence the burden of RD. In our cohort, individual polymorphisms on angiogenesis (VEGFA), extracellular matrix degradation (MMP3) and innate immunity activation (TLR3) pathways were independent predictive factors of RD. These markers, whether validated, might underline the role of host genetics factors in predicting R0. Moreover, if VEGFA-rs2146323 variant carriers could benefit the most from bevacizumab appears as an intriguing question. Legal entity responsible for the study: Toffoli Giuseppe. Funding: Has not received any funding. Disclosure: F. Puglisi: Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: