Legal entity responsible for the study: The authors. Funding: Has not received any funding.
Disclosure:All authors have declared no conflicts of interest.
780P Effect of neoadjuvant chemotherapy on the programmed death-1 pathway in esophageal and gastric cancer
M.C. Svensson1 , A. Linde´n1 , J. Nygaard1 , C. Hedner1 , B. Nodin1 , D. Borg1 , K. Leandersson2 , K. Jirstro¨m1 1
Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden,2
Cancer Immunology, Department of Translational Medicine, Lund University, Malmo¨, Sweden, Lund University, Lund, Sweden
Background: Esophageal and gastric (EG) cancers stand for a considerable amount of cancer cases and deaths worldwide. Although addition of neoadjuvant and/or adjuvant therapy has led to an improved survival in patients with resectable tumours, there is still a great unmet need for novel treatment strategies and complementary biomarkers. This study examined the effect of neoadjuvant chemotherapy on the expression of pro-grammed death receptor 1 (PD-1) and propro-grammed death ligand 1 (PD-L1) in EG adenocarcinoma, as well as the associations of PD-1 and PD-L1 expression with histo-pathological response and clinical outcome.
Methods: Immunohistochemical expression of PD-1 on tumour-infiltrating immune cells (TIC) and of PD-L1 on tumour cells (TC) and TIC was assessed on paired pre-treatment biopsies, post-pre-treatment resected primary tumours and a subset of paired lymph node metastases from a consecutive cohort of 148 patients with neoadjuvant þ/- adjuvant treated EG adenocarcinoma.
Results: PD-1 expression was significantly higher in resected tumours and in lymph node metastases compared to biopsies, but the expression of PD-L1 TC and PD-L1 TIC was similar before and after neoadjuvant therapy. PD-1 expression was not associated with histopathological response or with survival. Positive PD-L1 TC expression in biopsies was significantly associated with histopathological response but not with sur-vival, whereas positive PD-L1 TC expression in resected tumours signified a reduced overall survival. High PD-L1 TIC expression in biopsies, but not in resected tumours, was significantly associated with a prolonged overall survival.
Conclusions: Expression of PD-1, but not of PD-L1, is augmented after neoadjuvant treatment. Chemotherapy may however evoke more resistant subsets of PD-L1 positive TC, thus indicating a need for alternative treatment strategies in the adjuvant setting. Legal entity responsible for the study: Lund University.
Funding: SUS Stiftelse och Donationer Fru Berta Kamprads Stiftelse Vetenskapliga ra˚det, Projektmedel fo¨r forsknings- och Utvecklingsarbete.
Disclosure:All authors have declared no conflicts of interest.
781P A user-friendly nomogram to predict relapse-free survival (RFS) in western patients with resected gastric cancer (GC)
M. Salati1 , S. Pipitone2 , M. Rimini1 , F. Gelsomino1 , A. Casadei-Gardini1 , K. Andrikou1 , F.M. Schipilliti1, G. Cortesi3, L. Cassanelli1, E. Caffari1, F. Serra4, A. Ricciardolo4, N. De Ruvo4, R. Gelmini4, S. Cascinu3, A. Spallanzani3
1
Medical Oncology, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy,2Oncologia Medica, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy,3Department of Oncology and Hematology, Azienda Ospedaliero -Universitaria Policlinico di Modena, Modena, Italy,4Surgical Oncology, Azienda Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy
Background:Despite multimodality treatment, in the Western world > 50% of GC patients relapse following curative-intent surgery and succumb to their disease. The absolute survival benefit of perioperative or adjuvant chemotherapy ranges from 6 to 15% at 5 years and must be balanced against treatment-related toxicities. Reliable tools to risk-stratify patients are lacking. The aim of this study was to build a practical tool to guide daily decision-making and clinical trial design.
Methods:Data of patients undergoing curative-intent surgery for T2-4 and N-positive GC between 2008 and 2018 at the Modena Cancer Centre were retrieved.
Clinicopathologic and biochemical parameters deemed of potential interest were col-lected. The cut-off value for continuos variables was assessed at 75percentile.
Univariate and multivariate Cox proportional-hazard models were used to assess the prognostic value of covariates. Based on the multivariate model, a nomogram to pre-dict 2- and 3-year RFS was developed with a corresponding number of points assigned to a given magnitude of the variable.
Results:A total of 157 patients were eligible for the analysis. 51% (n¼ 80) were female and 88% (n¼ 139) had an ECOG PS of 0-1. Only 6% of cases were gastroesophageal junction cancers. 13% (n¼ 20), 25% (n ¼ 40), 62% (n ¼ 97) presented at diagnosis with stage I, II and III, respectively. Adjuvant chemotherapy was administered to 49% of patients. Out of 15 covariates tested, the following were independent predictors of outcome in the multivariate analysis and therefore included in the nomogram: ECOG PS (HR 2.51; p¼ 0.006), nodal status (HR 3.04; p ¼ 0.078), angioinvasion (HR 2.62; p¼ 0.005) and logNeutrophil/Lymphocyte ratio (HR 3.50; p < 0.001).
Conclusions:We built an easy-to-use nomogram to estimate 2- and 3-year individual RFS probability in resected GC. Interestingly, this tool incorporates variables reflecting
patients characteristics (ECOG PS), tumour aggressiveness (nodal status and angioin-vasion) and immune-inflammation status (NLR). This nomogram could assist clini-cians in discussing with patients prognosis and the risk-to-benefit ratio of systemic treatment as well as the design of future trials.
Legal entity responsible for the study:Massimiliano Salati. Funding:Has not received any funding.
Disclosure:All authors have declared no conflicts of interest.
782P Efficacy and toxicity of weekly carboplatin and paclitaxel as induction or palliative treatment in advanced esophageal cancer patients F.M. de Man, R.A.G. Van Eerden, E. Oomen-de Hoop, J.N. Veraart, N. van Doorn, L. van Doorn, A. van der Gaast, R.H.J. Mathijssen
Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
Background: Half of all patients with esophageal cancer present with advanced disease at diagnosis. The most optimal treatment for this group has not been identified yet. Therefore, we evaluated a weekly regimen of carboplatin for 6 cycles (area under the curve (AUC) of 4)þ paclitaxel 100mg/m2as induction (iCT) or palliative treatment (pCT). Methods: All patients with advanced (gastro-) esophageal cancer treated with this regi-men between 2002-2018 at the Erasmus MC Rotterdam were included. Patients who received radiotherapy or were treated elsewhere were excluded. Data on toxicity, response, and survival were collected from patient records. Analyses were performed in 2 groups: iCT or pCT. Median progression free survival (PFS) and median overall sur-vival (OS) were estimated with the Kaplan-Meier method.
Results: A total of 291 patients was included (iCT:122; pCT:169). Most patients had T3 carcinoma (iCT:54%; pCT:66%), and stage IV disease (iCT:42%; pCT:91%). The majority of the tumors were adenocarcinomas (iCT:50%; pCT:70%) and located at the distal esophagus (iCT:47%; pCT:73%). Incidence of severe grade3 gastrointestinal toxicity was low (iCT:3%; pCT:5%). Grade3 toxicity occurred mainly as hematologi-cal toxicity (iCT:71%; pCT:73%) with grade3 neutropenia of 43% and grade 4 of 25% in both groups. Nonetheless, only 3% of patients experienced febrile neutropenia. Premature termination of the planned cycles due to toxicity occurred in 12% of the iCT group and 17% of the pCT group. Cycle delay due to toxicity occurred in 42% (iCT) and 43% (pCT) of the patients. Sensory neuropathy was low-graded and seen in 25% (iCT) and 26% (pCT) of the patients. Overall response rates were 48% (iCT) and 44% (pCT). Esophagectomy or definitive chemoradiotherapy followed in 42% of iCT, resulting in a PFS of 22.1 months (interquartile range (IQR): 12.4-114.2) and OS of 26.8 months (IQR: 15.4-91.7). For pCT, PFS was 8.2 months (IQR: 5.1-14.5) and OS 10.9 months (IQR: 6.5-18.3).
Conclusions: Weekly carboplatin (AUC4) and paclitaxel (100mg/m2) as an outpatient regimen is well-tolerated and an effective induction or palliative treatment regimen for patients with locally advanced or metastatic disease.
Legal entity responsible for the study: A.H.J. Mathijssen. Funding: Has not received any funding.
Disclosure:R.H.J. Mathijssen: Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): Cristal Therapeutics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pamgene; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi; Honoraria (institution): Servier; Honoraria (institution): Novartis; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Astellas. All other authors have declared no conflicts of interest.
783P Perioperative chemotherapy with docetaxel, oxaliplatin, fluorouracil and leucovorin (FLOT) versus epirubicin, platinum and capecitabine or flourouracil (EOX/ECF) in resectable gastric or gastroesophageal junction adenocarcinoma: Safety and response data from India T. Chawla1 , R. Thambudorai2 , A. Ashok3 , B. Roy2 , J. Ghosh4 , S. Ganguly4 , P. Roy5 , M. Mallath4 1
Clinical Pharmacology, Tata Medical Center, Kolkata, India,2
GI-HPB Surgery, Tata Medical Center, Kolkata, India,3
Thoracic Surgery, Tata Memorial Hospital, Mumbai, India,4
Medical Oncology, Tata Medical Center, Kolkata, India,5
Pathology, Tata Medical Center, Kolkata, India
Background: Gastric and GEJ cancers are one of the top four cancers in India with poor 5-year survival. Post ASCO 2017, we switched to docetaxel-based peri-operative chemotherapy (FLOT) which is the new standard of care. In this audit, we report the pathological response and toxicity of FLOT compared to our older standard (EOX/ ECF).
Methods: We analysed our database of 118 patients with gastric or GEJ adenocarci-noma treated at our center from May 2011 to April 2019. 85 patients (72%) received perioperative chemotherapy with three pre-operative and three post-operative 3-week cycles of either EOX (50mg/m2 Epirubicin and 130mg/m2 Oxaliplatin on Day 1 plus 1250mg/m2 Capecitabine for 21 days) or ECF (50mg/m2 Epirubicin and 60mg/m2 Cisplatin on Day 1 plus 800mg/m2/day Fluorouracil as continuous intravenous infu-sion for 5 days). 33 patients (28%) received four pre-operative and four post-operative
