2OStrategic inhibition of CEP55 in aggressive breast cancer leads to mitotic catastrophe
ConclusionsCollectively, we propose a novel treatment strategy of MEK1/2 -PLK1 dual combination for selectively targeting CEP55 over-expressing BC in the clinics.Legal entity responsible for the studyThe author.FundingNHMRC.DisclosureThe author has declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

235PStudy on the socioeconomic and clinical factors affecting the proportion of breast conserving surgery in Chinese women breast cancer
This study intends to investigate the socioeconomic and clinical factors affecting the proportion of breast conserving surgery (BCS) in China.MethodsA total of 51237 breast cancer patients were treated in Tianjin Medical University cancer institute&Hospital from January 2005 to January 2018. In order to improve the success rate of BCS, we choose 5660 patients prepared to be treated by BCS to make analysis of independent factors affecting initial positive margins. Finally, we analyzed the survival trend of breast cancer patients after increasing the proportion of BCS by comparing the locoregional free survival (LRRFS), ...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

457PFirst-in-human study of ABBV-621 in patients (pts) with previously treated sold tumours: Dose-optimization cohorts
ConclusionsAdministration of ABBV-621 in pts with R/R CRC and pancreatic cancer shows an acceptable safety profile at all DL and evidence of antitumor activity.Clinical trial identificationNCT03082209.Editorial acknowledgementMedical writing support was provided by Yanci M. Baker, PhD, from Aptitude Health, Atlanta, GA, and funded by AbbVie.Legal entity responsible for the studyAbbVie Inc.FundingAbbVie Inc.DisclosureE. Calvo: Honoraria (self): HM Hospitales Group; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Nanobiotix; Advisory / Consu...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1130PSevere oral mucositis (SOM) mitigation by genetically modified lactococcus lactis bacteria (LLB) producing human trefoil factor 1 (hTFF1; AG013) in patients being treated with concomitant chemoradiation (CRT) for oral and oropharyngeal cancers (OCOPC)
ConclusionsObservations based on blinded data suggest that AG013 offers a safe, well-tolerated, and potentially efficacious platform to deliver an effective protein intervention for SOM mitigation.Clinical trial identificationAG013-ODOM-201.Legal entity responsible for the studyOragenics, Inc.FundingOragenics, Inc.DisclosureS. Sonis: Advisory / Consultancy, consultant: Oragenics. All other authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1577PAnalysis of the tumour microenvironment and tumour genotype through different stages of lung adenocarcinoma
ConclusionsSupporting the concept of TP53 as a passenger mutation, we detected significantly more TP53 mutations in late stage disease. In addition, we found a pronounced B cell response in tumors carrying driver mutations. Characterization of the tumor microenvironment might become an integral part of biomarker assessment in solid tumors in the future.Legal entity responsible for the studyHematopathology Hamburg.FundingHas not received any funding.DisclosureM. Tiemann: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory /...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

236PClinical decision making and multidisciplinary team meetings (MDMs) in early breast cancer. Is the agreement between planned and applied therapeutic program?
ConclusionsThe results of our study could be useful for enhance the role of MTD and identify unmet needs in decision making process in EBC.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1578PDoes progress achieved in the treatment of patients with metastatic non-small cell lung cancer (NSCLC) reach the elderly population?
AbstractBackgroundAlthough treatment modalities for non-small cell lung cancer (NSCLC) are rapidly evolving, there is insufficient evidence that novel drugs reach elderly patients (aged ≥ 70 years) and improve their outcomes. The purpose of this study was to evaluate the access to treatment in the elderly population with stage IV NSCLC in a real life setting and its impact on survival (OS) over the past 10 years.MethodsWe compared elderly and younger patients with stage IV NSCLC treated at our tertiary cancer centre and its affiliated smaller hospitals. We collected patients and tumor characteristics such as age at diag...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

458PSafety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
ConclusionsBAY is well tolerated as anticipated due to specificity for mIDH1. BAY inhibited mIDH1-R132X activity as evidenced by a PD effect in pts with measurable 2-HG, with objective response in 3 pts (all gliomas).Clinical trial identificationNCT02746081.Editorial acknowledgementMedical writing assistance was provided by Laura Valenzo, PhD, of Complete Health Vizion and funded by Bayer AG.Legal entity responsible for the studyBayer AG.FundingBayer AG.DisclosureW. Wick: Non-remunerated activity/ies, patent: IDH vaccine; Non-remunerated activity/ies, patent: IDH diagnostic; Non-remunerated activity/ies, patent: APG diagno...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1131PTranscriptome signatures of treatment responses in a preoperative window of opportunity trial of nivolumab and tadalafil in resectable squamous cell carcinoma of the head and neck
ConclusionsThese results point to diverse intratumoral immune states triggered by nivolumab/tadalafil in HPV(+) when compared to HPV(-) SCCHNs. They challenge the notion that increased presence of intratumoral T lymphocytes alone is associated with favorable therapeutic responses to PD1 inhibition in SCCHN. Yet, select pretreatment transcripts associated with innate and/or adaptive immune responses may have prognostic relevance.Clinical trial identificationNCT 03238365.Legal entity responsible for the studyThe authors.FundingBristol-Myers Squibb.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

3OSystemic gut microbial metabolites limit the anti-tumour effect of CTLA-4 blockade in hosts with cancer
ConclusionsAltogether, these results suggested that gut microbial metabolites might favor an immune tolerance profile that limits anti-CTLA-4 activity.Legal entity responsible for the studyInstitut Gustave Roussy.FundingThis study was funded by Gustave Roussy Cancer Campus, Fondation Gustave Roussy, the Institut national de la sant é et de la recherche médicale (INSERM), the Centre national de la recherche scientifique (CNRS), SIRIC SOCRATE (INCa DGOS INSERM 6043), SIRIC SOCRATE 2.0 (INCa-DGOS-INSERM_12551), MMO program: ANR-10IBHU-0001); Direction General de l’Offre de Soins (DGOS; TRANSLA 12-174); Ins...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

459PProof of concept clinical study by US-guided intratumor injection of VCN-01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer
ConclusionsVCN-01 replicates and expresses hyaluronidase after intratumor injection both in preclinical models and in patients with pancreatic cancer. Enhanced chemotherapy access and reduction of tumor stiffness favours local control of pancreatic tumours treated with VCN-01 + standard of care.Clinical trial identificationEudraCT: 2012-005556-42.Legal entity responsible for the studyVCN Biosciences.FundingVCN Biosciences.DisclosureM. Hidalgo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Advisory...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1579PPrognostic factors for non-small cell lung cancer patients with driver mutation negative and brain metastases (HOT 1701)
This study aimed to identify prognostic factors and clarify the survival in NSCLC patients with BM at the time of a diagnosis.MethodsA total of 566 NSCLC patients with BM from 15 institutions between January 2008 and December 2014. Among them, 176 patients had driver mutation, such as EGFR mutation and ALK-rearrangement, and 390 patients did not. This retrospective study focused on the 390 NSCLC patients without driver mutation, and identified clinical prognostic factors using Cox proportional hazards model. Moreover, we validated the disease specific Graded prognostic assessment (DS-GPA) in this cohort.ResultsMedian OS wa...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

237PThe value of genetic counselling in breast cancer genetic testing and clinical management
ConclusionsGenetic counselling provides significant psychosocial and practical benefits in the provision of breast cancer genetics: including advice for the whole family, ensuring genetic testing is appropriate and referral to appropriate external healthcare agencies. 1 NICE Guidance 2 NCCN Guidelines.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureV. Kiesel: Shareholder / Stockholder / Stock options: Genehealth UK. G. Wishart: Shareholder / Stockholder / Stock options: Check4Cancer. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

460PA phase Ia/b first-in-human, open-label, dose-escalation, safety, PK and PD study of TP-0903 in solid tumours
ConclusionsThe oral small molecule AXL kinase inhibitor TP-0903 is well tolerated with a manageable safety profile. Hematologic toxicity was observed as a DLT. Future studies will evaluate the role of TP0903 in selected disease cohorts as monotherapy and in combination. Serum soluble AXL will be evaluated as a potential predictive biomarker of response.Clinical trial identificationNCT: 02729298.Legal entity responsible for the studyTolero Pharmaceuticals, Inc.FundingTolero Pharmaceuticals, Inc.DisclosureJ. Sarantopoulos: Research grant / Funding (institution): Tolero. G. Fotopoulos: Research grant / Funding (institution): ...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1580PA novel risk classification system based on nomogram scores to predict survival of patients presenting with brain metastases at the first diagnosis of NSCLC
ConclusionsWe established a risk stratification system based on nomogram scores to predict the OS of patients presenting with BMs at initial diagnosis of NSCLC. These predictive models can act as auxiliary tools to guide treatment strategies and prognostic evaluation.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1132PRisk and impact of renal impairment of locally advanced head and neck squamous cell carcinoma patients who received chemoradiotherapy with cisplatin
AbstractBackgroundRisk factors of cisplatin induced acute kidney injury (AKI) patients has been well described. In HNSCC, an incidence of cisplatin induced AKI was observed in 34.2%. Most studies reported AKI as a surrogate endpoint. However, delayed cisplatin induced nephrotoxicity and long-term renal outcomes were not well studied.MethodsLocally advanced HNSCC patients treated between 1/2007 and 12/2018 who underwent definitive or post-operative chemoradiotherapy (CRT) with cisplatin were identified. Patient characteristics, treatments, creatinine at baseline, during, 3, 6, and 12 months after CRT completion were retrosp...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

4ONovel dendritic cell based immunotherapy for advanced cancer
AbstractBackgroundImmune-checkpoint inhibitors (ICI) such as Ipilumimab and Nivolumab have made long-term survival a real possibility for advanced cancer patients. Despite the success, only a proportion of patients receiving ICI show meaningful clinical benefit. Developing a more personalized treatment strategy using patient ’s own immune cells may be a promising approach for treating non-responding patients. Natural circulating dendritic cells (nDC) such as CD1c+ DC (cDC2) subset and plasmacytoid DC (pDC) are essential for efficient activation of immune responses after ICI therapy. Thus understanding the condition o...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

238PElderly patients in the Japanese breast cancer registry
AbstractBackgroundAim: To clarify the clinicopathological characters and treatments and prognosis in elderly breast cancer patients using the Japanese Breast Cancer Registry (JBCR) system.MethodsWe reviewed data from JBCR, which is the nation-wide registry of newly diagnosed and operated primary breast cancer patients in Japan. To clarify its characteristics, we compared elderly patients aged 75 and over (elderly) with aged from 65 to 74 (young-old; y-o) and that from 55 to 64 (post-menopausal; p-m), respectively.ResultsIn total 132,240 cases diagnosed between 2004 and 2011 were reviewed (elderly; n  = 27,385...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

461PFirst in human phase I/IIa study of PEN-866, a heat shock protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumours: Phase I results
ConclusionsPEN-866 appears well tolerated with an expected adverse event profile and preliminary evidence of antitumor activity. PEN-866 will be evaluated in phase 2a expansion cohorts (NCT03221400).Clinical trial identificationNCT03221400 July 18, 2017.Legal entity responsible for the studyTarveda Therapeutics, Inc.FundingTarveda Therapeutics, Inc.DisclosureJ.C. Bendell: Research grant / Funding (institution): Tarveda Therapeutics; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Advisory/Consultancy to Institution: Gilead; Advisory / Consultancy, Research grant / Funding ...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1133PSystemic bevacizumab for the treatment of recurrent respiratory papillomatosis: A retrospective analysis from an academic tertiary care center
ConclusionsSystemic bevacizumab appears to be a safe and well tolerated treatment option for patients with severe RRP. It demonstrates promising efficacy on symptoms including voice quality and improved breathing as well as decreased requirement for surgical therapy.Legal entity responsible for the studyThe author.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1581PComparison of real-world response rate (rwRR) to RECIST-based response rate in patients with advanced non-small cell lung cancer (aNSCLC)
ConclusionsData curated from EHRs of rw patients with aNSCLC can provide estimates of response rates that are comparable to RECIST-based response rates observed in similar patient populations studied in clinical trial settings. These findings demonstrate the potential of leveraging rw cohorts as a comparator to single arm clinical trials in oncology.Legal entity responsible for the studyFlatiron Health, Inc.FundingFlatiron Health Inc., independent subsidiary of the Roche group.DisclosureX. Ma: Full / Part-time employment, Flatiron Health, Inc. is an independent subsidiary of the Roche Group.: Flatiron Health, Inc.; Shareho...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

239PTumour-infiltrating lymphocytes and BRCA-like status in stage III breast cancer patients treated with intensified carboplatin-based chemotherapy
AbstractBackgroundThe prognostic value of tumour-infiltrating lymphocytes (TILs) differs by breast cancer (BC) subtype. The aim of this study was to evaluate TILs in stage III BC in the context of BRCA1/2-like phenotypes and their association with outcome and benefit of intensified platinum-based chemotherapy.MethodsPatients in this study participated in a randomized controlled trial of adjuvant intensified platinum-based chemotherapy versus conventional anthracycline-based chemotherapy carried out between 1993-1999 in stage III BC. Stromal TILs were scored according to International guidelines in these HER2-negative tumou...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

5PDThe role of EGFR inhibitor (EGFRi) in immune cell infiltration and CD8+ T-cell activation in EGFR mutant lung cancer
ConclusionsThese results provide evidence that EGFRi has the capacity to facilitate modulation of the tumor microenvironment to favor immune cell infiltration and promote T-cell mediated antitumor immunity.Legal entity responsible for the studyThe University of Texas MD Anderson Cancer Center.FundingTianjin HengJia Biotechnology Development Co., Ltd.DisclosureF. Li: Shareholder/Stockholder/Stock options: Tianjin HengJia Biotechnology Development Co., Ltd.. G. Lizee: Advisory/Consultancy: HengJia Neoantigen Biotechnology (Tianjin) Co., Ltd.. P. Hwu: Advisory/Consultancy: Dragonfly Therapeutics; Advisory/Consultancy: GlaxoSm...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

462PA phase I open-label, non-randomized study of recombinant super-compound interferon (rSIFN-co) in patients with advanced solid tumours
ConclusionsThe RP2D of rSIFN-co was 30ug (1.6  × 107IU) 3x/week for 21days followed by 7 days ’ rest. Anti-tumour activity seen in heavily pre-treated advanced solid tumor patients. especially in HCC. Future plans involve combinations with other immunotherapies.Clinical trial identificationNCT02387307.Legal entity responsible for the studySichuan Huiyang Life Science and Technology Corporation.FundingSichuan Huiyang Life Science and Technology Corporation.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

240PUnravelling the biological characteristics of MammaPrint extreme risk subgroups
In this study, we aim to gain more insight into their biological significance using differentially expression genes (DEGs) analysis.MethodsWe selected 400 samples from the whole MP range and defined 4 subgroups (Ultra high [UH], High risk [HR], Low risk [LR], Ultra low [UL]), for which FFPE microarray full-transcriptome data were available at Agendia. DEGs analysis was performed with limma and subsequent pathway analysis with Enrichr and GOrilla.ResultsTwo separate comparative analyses were carried out to unravel biological processes associated with extreme risk subgroups: UL vs. LR and UH vs. HR. We found 101 DEGs (logFC ...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

6PDThe mutational signature of spontaneously developing tumours in MLH1-/- mice: Potential consequences for immunotherapeutic approaches
ConclusionsThe present study is the first reporting results of a comparison between different spontaneously developing tumors as models for MMR-D driven tumorigenesis. Additionally to identifying ARID1A as causative mutation hotspot, this comprehensive characterization of the mutational landscape may be a good starting point to predict antigens for vaccination approaches.Legal entity responsible for the studyThe authors.Fundinggerman research foundation (DFG); grant number: MA5799/2-1.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1134PMonalizumab in combination with cetuximab in patients (pts) with recurrent or metastatic (R/M) head and neck cancer (SCCHN) previously treated or not with PD-(L)1 inhibitors (IO): 1-year survival data
ConclusionsIn a cohort of 40 patients of heavily pretreated SCCHN patients, monalizumab and cetuximab combination demonstrated high response rate, good duration of response, and promising PFS and OS as well as good safety profile. An additional R/M SCCHN cohort of 40 patients who received both platinum-based chemotherapy and IO is being enrolled in this study.Clinical trial identificationNCT02643550.Legal entity responsible for the studyInnate Pharma.FundingInnate Pharma.DisclosureR.B. Cohen: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Innate Pharma; Honoraria (self), Advisory / Consul...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1582PEstimating the cost and survival impact of new aNSCLC therapies in Canada with the iTEN model
AbstractBackgroundNovel therapies are replacing established treatment options for patients with advanced non-small cell lung cancer (aNSCLC), which poses a challenge to healthcare budgets. The impact of Treatment Evolution in NSCLC (iTEN) model is a validated discrete event patient simulation designed to estimate the impact of treatment sequencing in aNSCLC. The impact of five novel therapies (osimertinib, alectinib, brigatinib, dabrafenib and trametinib, and pembrolizumab combination therapy) changing aNSCLC management in Canada was modelled.MethodsCurrent Canadian treatment practices were established via a modified Delph...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

241PResidual cancer burden as a prognostic factor in a large series of neoadjuvant chemotherapy. Subgroup analysis per molecular surrogated subtypes
ConclusionsIn our large series the RCB is reproducible as a surrogate of survival special in those chemo sensitive tumors such as Her2 and triple negative ones.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

463PEvaluation of pharmacodynamic (PD) biomarkers in advanced cancer patients treated with oxidative phosphorylation (OXPHOS) inhibitor, OPC-317 (OPC)
ConclusionsWe identified novel tumor/blood PD biomarkers with clear evidence of target modulatory effects at clinically tolerable doses of OPC. With validation, they can aid the clinical development of OXPHOS inhibitors as a novel class of cancer therapy.Clinical trial identificationNCT03158324.Legal entity responsible for the studyOtsuka Pharmaceutical Co. Ltd.FundingOtsuka Pharmaceutical Co. Ltd.DisclosureD.S. Tan: Honoraria (self): Roche; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): MSD; Honoraria (self): Genmab; Honoraria (self), Research grant / Funding (institution): AstraZeneca;...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

7PDSynergistic anti-cancer activity of auranofin with anti-PD-L1 therapy in triple negative breast cancer
ConclusionsOur data provides a novel therapeutic strategy using auranofin in combination with anti-PD-L1 antibody for TNBCs and warrants further clinical investigation for TNBC patients. Since the success rate of anti-PD-L1 therapy is very low in TNBC patients, our data provides a novel strategy to use auranofin with anti-PD-L1 therapy to that may enhance the efficacy of immune checkpoint therapy in TNBC patients.Legal entity responsible for the studyThe authors.FundingCure Cancer Australia& Can Too Foundation Project grant [ID 1147230] to Prahlad Raninga National Health& Medical Research Council (NH&MRC) Progr...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

242PClinical validation of CanAssist breast in a Spanish cohort
ConclusionsCAB performs well in stratifying risk of recurrence in this Spanish cohort with the data matching performance shown earlier with the mix of Asian and Caucasian patients. In the absence of any inter-mediate risk category in CAB, it offers a cost effective alternative to existing prognostic tests providing definitive results to plan treatment of early stage breast cancer patients.Legal entity responsible for the studyManjiri M. Bakre.FundingHas not received any funding.DisclosureM. Bakre: Leadership role, Full / Part-time employment, Officer / Board of Directors, CEO and Founder: OncoStem Diagnostics Pvt Limted. (...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1135PUpdated results of a phase II study evaluating accelerator-based boron neutron capture therapy (AB-BNCT) with borofalan(10B) (SPM-011) in recurrent squamous cell carcinoma (R-SCC-HN) and recurrent and locally advanced non-SCC (R/LA-nSCC-HN) of the head and neck
ConclusionsThese data suggest that AB-BNCT with borofalan(10B) emerges as a promising treatment option for pts with R –SCC- HN or R/LA-nSCC-HN with no other treatment option.Clinical trial identificationJapicCTI-194640.Legal entity responsible for the studySumitomo Heavy Industries, Ltd, Stella Pharma Corporation.FundingFukushima prefectural subsidy for development and testing of global cutting-edge medical devices.DisclosureK. Hirose: Research grant / Funding (self), Travel / Accommodation / Expenses: Sumitomo Heavy Industries, Ltd; Travel / Accommodation / Expenses: Stella Pharma Corporation. K. Ono: Advisory / Con...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1583PSMARCA4 deficient non-small cell lung cancer (NSCLC): A comprehensive genomic profiling (CGP) study
AbstractBackgroundThe SMARCA4 catalytic ATPase, can be inactivated by several types of genomic alterations (GA) in NSCLC. SMARCA4 deficient (d) NSCLC is an aggressive subtype of primary lung adenocarcinoma that is often confused with metastatic disease to the lung.MethodsFrom a series of 40,319 clinically advanced NSCLC, 2,840 (7%) SMARCA4d and 37,479 (93%) SMARCA4i cases underwent hybrid capture-based CGP using FFPE material. Microsatellite instability (MSI) was determined on 114 loci and tumor mutational burden (TMB) and (mutations (mut) per/ Mb) was determined on 1.1 Mbp of sequenced DNA. PD-L1 expression was measured b...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

464PPharmacokinetic (PK) assessment of BT1718: A phase I/II a study of BT1718, a first in class bicycle toxin conjugate (BTC), in patients (pts) with advanced solid tumours
ConclusionsBT1718 is a first in class BTC which is generally well tolerated at the present dose level. Current plasma and tumor PK data are consistent with proposed preclinical mechanism of tumor targeted toxin delivery.Clinical trial identificationNCT03486730.Legal entity responsible for the studyCancer Research UK.FundingCancer Research UK and BicycleRD Limited.DisclosureN. Cook: Advisory / Consultancy: Tarveda Therapeutics; Advisory / Consultancy: Epigene Therapeutics. U. Banerji: Advisory / Consultancy: Astellas; Advisory / Consultancy: Novartis; Advisory / Consultancy: Karus Therapeutics; Advisory / Consultancy: Phoen...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

8PDAutomatic interpretation of cancer genomes creates the largest repository of tumour genetic driver events
ConclusionsAll the results and framework are available online to the cancer genomics research community atwww.intogen.org, which we envision can support a broad range of oncology use cases.Legal entity responsible for the studyInstitute for Research in Biomedicine (IRB, Barcelona).FundingMinisterio de Educaci ón y Ciencia de España (SAF-2015-R-66084 and RTI2018-094095-B-I00) Instituto Nacional de Bioinformática (INB) - PT17/0009/0013.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

243PMeta-analysis on association of pathological complete response with long-term survival outcomes in triple-negative breast cancer
ConclusionsThis study confirms the strong association between pCR and survival outcomes in TNBC based on evidence synthesis from both clinical and real-world settings. In addition, this study suggests potential survival benefit of subsequent adjuvant therapy for TNBC patients who received neoadjuvant therapy.Legal entity responsible for the studyMerck& Co., Inc.FundingMerck& Co., Inc.DisclosureP.A. Fasching: Advisory / Consultancy: Merck& Co., Inc. M. Huang: Full / Part-time employment: Merck& Co., Inc. J. Cort és: Advisory / Consultancy: Merck& Co., Inc. J. Zhao: Full / Part-time employment: Mer...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1136PPhase III KEYNOTE-048 study of first-line (1L) pembrolizumab (P) for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Asia vs non-Asia subgroup (subgrp) analysis
ConclusionsP vs E showed favorable OS in Asia and non-Asia subgrps, regardless of PD-L1 status; responses were durable, particularly among all non-Asia subgrps; safety was favorable. P+C vs E showed favorable OS in pts with CPS ≥20 in Asia and non-Asia subgrps regardless of PD-L1 status, durable responses, and similar safety.Clinical trial identificationNCT02358031.Editorial acknowledgementDoyel Mitra, PhD, and Dana Francis, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA), funded by Merck Sharp& Dohme Corp., a subsidiary of Merck& Co., Inc., Kenilworth, NJ, USA.Legal entity responsible for the studyM...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

9PDAurora-B mediated snail phosphorylation is essential for mitotic spindle checkpoint and for preventing chromosomal instability in breast cancer
Conclusions1. Snail is required for mitotic spindle checkpoint activation; 2. Snail is phosphorylated by Aurora B in mitosis; 3. Aurora-B medicated Snail phosphorylation is required for optinal activation of the spindle checkpoint and prevention of chromosomal instability in breast cancer.Legal entity responsible for the studyThe authors.FundingTianjin Medical University Cancer Institute and Hospital.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1584PExploring resistance to nivolumab [NIV] applying an Immune Genomic Signature (IGS) in advanced pretreated NSCLC [PRINCiPe study]
ConclusionsThe identified IGS was able to select APNSCLC pts with a significant lower chance to benefit from NIV, supporting the existence of an intrinsic genomic-detectable resistance. Further analyses are ongoing, including a comprehensive transcriptome analysis.Legal entity responsible for the studyEmilio Bria.FundingUniversity of Verona.DisclosureS. Pilotto: Honoraria (self): AstraZeneca, BMS, Roche, MSD, Boeringher Ingelheim; Research grant / Funding (self): AIRC ; Travel / Accommodation / Expenses: BMS, Roche, AstraZeneca, Boeringher Ingelheim. M. Milella: Honoraria (self): Pfizer, EUSA Pharma, AstraZeneca. E. Bria: ...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

465PA phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumours
ConclusionsThrough all doses tested thus far, VT1021 has been shown to be safe for patients and induces expression of Tsp-1.Clinical trial identificationNCT03364400 December 6, 2017.Legal entity responsible for the studyVigeo Therapeutics, Inc.FundingVigeo Therapeutics, Inc.DisclosureS. Wang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Vigeo Therapeutics, Inc. K. Kerstein: Full / Part-time employment: Vigeo Therapeutics, Inc. G. Berk: Advisory / Consultancy: Vigeo Therapeutics, Inc. M.J. Cieslewicz: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Vigeo Th...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

244PImmune infiltrate composition across intrinsic subtypes in hormone receptor (HR)+/HER2- early breast cancer (BC) enrolled in the prospective LETLOB trial
ConclusionsIn HR+/HER2- early BC, non-luminal subtypes show higher TIL levels and a more pro-inflammatory anti-tumour immune infiltrate composition. This immune heterogeneity across intrinsic subtypes should be considered when analysing the complex prognostic role of TILs in HR+/HER2- early BC.Clinical trial identificationNCT00422903.Legal entity responsible for the studyUniversity of Padua.FundingGlaxoSmithKline funded the clinical trial (LETLOB) including gene-expression analysis; DOR grants 1721185/17 and 1830512/18 from the University of Padua.DisclosureM.V. Dieci: Advisory / Consultancy: EliLilly; Advisory / Consultan...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1137PIntegrated data review evaluating safety, pharmacokinetics (PK) and immunogenicity of RM-1929 photoimmunotherapy (PIT) in subjects with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC)
ConclusionsThe integrated clinical safety data indicated that RM-1929 PIT treatment had a favorable safety profile with no unexpected safety concerns.Clinical trial identificationNCT02422979.Legal entity responsible for the studyRakuten Medical, Inc.FundingRakuten Medical, Inc.DisclosureJ.M. Johnson: Advisory / Consultancy: Foundation Medicine; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca. J.M. Curry: Research grant / Funding (institution): AstraZeneca. S.T. Kochuparambil: Shareholder / Stockholder / Stock options, Full / Par...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

245PFrequency of germline mutations in women ’s cancer susceptibility genes in a large cohort of Chinese breast cancer patients
ConclusionsOur study derived the prevalence of P/LP germline mutation in 524 Chinese BC patients and 11% were found to have a germline mutation. We explored the characteristics of tumor somatic mutations in germline mutations carriers, which provided a better understanding of patients with germline mutations.Legal entity responsible for the studyNing Liao.FundingNational Natural Science Foundation of China (Grant No. 81602645), Guangdong Provincial Natural Science Foundation (Grant No. 2016A030313768).DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1585PDNA damage repair deficiency is associated with early resistance to crizotinib: Whole-genome analysis in non-small cell lung cancer patients with ALK-fusion
AbstractBackgroundALK-tyrosine kinase inhibitor (TKI) is associated with a favarable survival benefit in ALK-fusion patients in advanced non-small cell lung cancer (NSCLC). However, almost 20% patients with TKI early resistance (progression-free survival is shorter than six months while treated by either crizotinib or second-line TKIs), show a poor survival with no more than one year. The mechanisms of early resistance to TKIs are unknown. Reliable biomarkers are required to predict the response to ALK-TKIs, especially in the early resistance. So we investigated genomic variations associated with responses to crizotinib in...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

466PInterim results from trial of SL-801, a novel XPO-1 inhibitor, in patients with advanced solid tumours
ConclusionsSL-801 reversibly binds XPO1, a clinically validated target in oncology. To date 27% of heavily pre-treated patients have achieved SD as best response. Enrollment and dose escalation continue.Clinical trial identificationNCT02667873.Legal entity responsible for the studyStemline Therapeutics.FundingStemline Therapeutics.DisclosureJ. Wang: Speaker Bureau / Expert testimony: AstraZeneca. E. Chiorean: Research grant / Funding (institution): Boehringer-Ingelheim, Merck, BMS, Lilly, Stemline, Ignyta/Roche, Incyte, Halozyme; Advisory / Consultancy: AstraZeneca, Array, Ipsen, Eisai, Halozyme, Seattle Genetics, Vicus, F...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

10PDevelopment of chimeric antigenic receptor (CAR) against VEGFR2 for solid tumour treatment
ConclusionsThe cytotoxicity assay showed that the VEGFR2-overexpressed FS293 cells were apparently killed by VEGFR2-CART cells. The antitumor effects of the VEGFR2-CART cells have been proved in a murine tumor model, suggesting that targeting VEGFR2 with CART cells can be a novel strategy in cancer immunotherapy.Legal entity responsible for the studyDevelopment Center for Biotechnology.FundingThe government of the Republic of China (Taiwan).DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

246PTriple blinded prospective study assessing the impact of genomics & amp; artificial intelligence Watson for oncology (WFO) on MDT ’s decision of adjuvant systemic therapy for hormone receptor positive early breast carcinoma
ConclusionsTumor board decision can be more scientific& evidence based with the help of genomics& a learnt colleague in the form of Watson for Oncology. Even though the clinical experience is the important determinant of adjuvant therapy, genomic test with artificial intelligence, which includes the scientific evidence, will guide in decision making. Long term follow up is needed for the validation in our clinical setting.Legal entity responsible for the studyManipal Hospital Ethical Committee.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

1138PFirst-line versus second-line immunotherapy in recurrent/metastatic squamous cell carcinoma of the head and neck
ConclusionsICI given as second line treatment were associated with similar OS but significant prolonged duration of response. We showed a trend to better OS in the cohort of pts who received ICI in second line setting (22 months).Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest. (Source: Annals of Oncology)
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research

247PPrognostic significance of progesterone receptor levels in luminal-like Her2- early breast cancer patients. A retrospective single cancer center analysis
AbstractBackgroundThe prognostic role of Progesterone receptor (PR) expression in early invasive breast cancer (BC) remains controversial. The aim of this retrospective analysis was to investigate the impact of PR expression levels on outcome of patients with luminal-like Her2 negative early BC.MethodsA population cohort of 441 primary invasive ER+/Her2- early BC patients from a single cancer center underwent surgery and received adjuvant endocrine therapy from 2000 to 2017 was retrieved. To assess the impact of the different PR levels on the prognosis, we calculated the Distant Free Survival (DFS) and the Breast Cancer Sp...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research