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CD226 has been reported to participate in the rescue of CD8+ T cell dysfunction. In this study, we aimed to assess the prognostic value of CD226 in tumor-infiltrating lymphocytes (TILs) derived from colorectal cancer (CRC) liver metastases treated with chemotherapy and radical surgery. TILs from 43 metastases were isolated and analyzed ex vivo using flow cytometry. CD155 and CD3 levels in the tumor microenvironment were assessed by immunohistochemistry. Exploration and validation of biological processes highlighted in this study were performed by bioinformatics analysis of bulk RNA-seq results for 28 CRC liver metastases pretreated with chemotherapy as well as public gene expression datasets. CD226 expression contributes to the definition of the immune context in CRC liver metastases and primary tumors. CD226 on CD8+ T cells was not specifically coexpressed with other immune checkpoints, such as PD1, TIGIT, and TIM3, in liver metastases. Multivariate Cox regression analysis revealed CD226 expression on CD8+ T cells to be an independent prognostic factor (p = 0.003), along with CD3 density at invasion margins (p = 0.003) and TIGIT expression on CD4+ T cells (p = 0.019). CD155 was not associated with the prognostic value of CD226. Gene expression analysis in a validation dataset confirmed the prognostic value of CD226 in CRC liver metastases but not in primary tumors. Downregulation of CD226 on CD8+ TILs in the liver microenvironment was restored by IL15 treatment. Overall, CD226 expression on liver metastasis-infiltrating CD8+ T cells selectively contributes to immune surveillance of CRC liver metastases and has prognostic value for patients undergoing radical surgery.

Pancreatic ductal adenocarcinoma (PDAC) is marked by molecular heterogeneity and poor prognosis. Among the stemness-related transcription factors, Spalt-like Transcription Factor 4 (SALL4) is correlated with unfavorable outcomes; however, its roles in PDAC remain unclear. SALL4

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study

An integrative approach taking into consideration the tumor microenvironment, in particular cancer-associated fibroblasts (CAFs) and tumor-infiltrating lymphocytes (TILs) and its interaction with tumor cells offers a more precise reflect of pancreatic ductal adenocarcinomas (PDACs) biology. In this setting, an immunomorphological signature established from bioinformatics data could thus represent an attractive approach. Moreover to molecular signatures, on which there is still no consensus. This study aimed to evaluate the prognostic value of a panel of morphological and immunohistochemical (IHC) markers on the immune, fibroblastic and epithelial contingents of PDACs for overall (OS) and relapse-free (RFS) survival. Two hundred and seventeen patients operated for PDAC between 2000 and 2017 were included for a tissue microarray (TMA) analysis. A panel of antibodies and special stains was selected based on a previous bioinformatics study (under review) literature data. Slides were digitized and lymphocytes expressing CD3, CD8 and CD20 were quantified. A pixel classifier was used to assess the percentage of collagen and fibroblasts expressing anti-LRRC15, HSP47, α-SMA and FAP antibodies involved in the stroma reaction. Due to the co-marking of stromal and epithelial cells of PTK7 and β-catenin, respectively implicated in embryogenesis and the canonical Wnt pathway, these markers were interpreted semi-quantitatively in a double-blind fashion. After dichotomization using the maximized log-rank method, the association of these parameters with OS and RFS was assessed by univariate and multivariate Cox models. Five years after surgical resection, 26 patients (12.0%) were free of recurrence and 56 (25.8%) were alive. In multivariate analysis, the following parameters were associated with reduced OS and RFS: poor differentiation, lymph node ratio greater than 0.2, loss of tumor β-catenin on tumor cells, a low density of tumor-infiltrating CD3 T lymphocytes and a high percentage of HSP47 fibroblasts. Reduced OS was also associated with an age greater than 65 years at the time of surgery and the absence of adjuvant treatment. In order to evaluate the joint effects of the three tumor compartments markers independentely related to OS and RFS (β-catenin, HSP47, CD3), we grouped them into 3 classes (0/1+, 2+, 3+) according to the number of good prognosis criteria (class 3+ with the greatest number of good prognosis criteria). The multivariate analysis shows an additive effect of these parameters in OS and RFS compared to class 3+ patients. These data underline the interest of simultaneously characterizing the three epithelial, immune and fibroblastic compartments in PDAC. Furthermore, we highlight for the first time the prognostic impact of HSP47 by immunohistochemistry and confirm the β-catenin one. This tissue approach with an IHC panel studied on an operating specimen could be a first step towards applicability on biopsies and lead to a better patient stratification in a therapeutic setting. Citation Format: Franck Monnien, Chloé Molimard, Marine Abad, Marie-Paule Algros, Sophie Félix, Nikolaus Zirganos, Bruno Heyd, Angélique Vienot, Christophe Borg, Frédéric Bibeau. Prognostic impact of an immunomorphological signature integrating immune, fibroblast and tumor markers in a series of 217 patients operated on for pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C064.

Simple Summary This is an exciting moment in clinical research in the squamous cell carcinoma of the anus (SCCA). Historical barriers regarding this disease are vanishing thanks to the creation of research networks in this rare pathology, gained knowledge in tumor biology and its environment in this human papillomavirus (HPV)-induced disease in more than 90% of patients, and the arrival of taxane-based chemotherapy regimens as well as immunotherapies and its novel combinations. This review sheds light on the present and the future of research on SCCA, new understanding of its rational for ongoing clinical trials, with special focus in locally advanced and metastatic diseases. Abstract Squamous cell carcinoma of the anus is an orphan disease, and after more than three decades of no substantial advances in disease knowledge and treatment, it is finally gaining momentum with the arrival of a taxane-based chemotherapy and immunotherapy. Currently, about 20 combination clinical trials with an anti-PD1/L1 are ongoing in localized and advanced stages, in association with radiotherapy, chemotherapy, tumor vaccines, anti-CTLA4, anti-EGFR, or antiangiogenic molecules. Moreover, a new biomarker with high sensitivity and specificity such as HPV circulating tumor DNA (HPV ctDNA) by liquid biopsy, is improving not only the prognostic measurement but also the treatment strategy guidance for this disease. Finally, better understanding of potential targets is reshaping the present and future clinical research in this unique, HPV genotype-16-related disease in the great majority of patients.

BACKGROUND: FOLFIRINOX has shown promising results in locally advanced (LAPA) or borderline resectable (BRPA) pancreatic adenocarcinoma. We report here a cohort of patients treated with this regimen from the AGEO group. METHODS: This is a retrospective multicentre study. We included all consecutive patients with non-pre-treated LAPA or BRPA treated with FOLFIRINOX. RESULTS: We included 330 patients (57.9% male, 65.4%

Biliary tract cancers (BTC) are a heterogeneous group of epithelial neoplasms, with a poor prognosis. Advanced BTC remains a challenging, non-curable disease. In this review, we provide an overview of the medical treatment options in advanced BTC and new strategies under development. Gemcitabine plus platinum chemotherapy is the standard first-line therapy in this setting. Recently, 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX) regimen became the only second-line therapy to be prospectively validated beyond failure of gemcitabine plus cisplatin combination in a phase III study, even though chemotherapy yielded modest survival improvement over best supportive care. Anti-epidermal growth factor receptor and antiangiogenic antibodies have not demonstrated any survival benefit in unselected patient populations. In recent years, knowledge about the molecular heterogeneity of BTC has considerably increased with the advent of large-scale genomic and transcriptomic analyses, opening up new perspectives for so-called personalised targeted therapies. Patients with BTC may be particularly good candidates for biomarker-driven strategies in clinical practice. Among current developments, the targeting of fibroblast growth factor receptor and isocitrate dehydrogenase gene alterations are the most promising avenues, and combination immunotherapies are under investigation.

Background Our study describes the feasibility and efficacy of a first-line FOLFIRINOX (5-fluorouracil [5FU], folinic acid, irinotecan, and oxaliplatin) induction chemotherapy (CT) followed by de-escalation as a maintenance strategy for advanced pancreatic cancer. Materials and Methods This multicenter retrospective study was conducted from January 2011 to December 2018. FOLFIRINOX de-escalation was defined as stopping oxaliplatin and/or irinotecan after at least four cycles of FOLFIRINOX, without evidence of disease progression. Maintenance schedules were fluoropyrimidine monotherapy (intravenous or oral [capecitabine]), FOLFOX (5FU, oxaliplatin), or FOLFIRI (5FU, irinotecan). Primary endpoint was overall survival (OS). Secondary endpoints were first progression-free survival (PFS1), second progression-free survival (PFS2), and toxicity. Results Among 321 patients treated with FOLFIRINOX, 147 (45.8%) were included. Median OS was 16.1 months (95% confidence interval [CI], 13.7–20.3) and median PFS1 was 9.4 months (95% CI, 8.5–10.4). The preferred maintenance regimen was FOLFIRI in 66 (45%) patients versus 5FU monotherapy in 52 (35%) and FOLFOX in 25 (17%) patients. Among 118 patients who received maintenance CT with FOLFIRI or 5FU, there was no difference in PFS1 (median, 9.0 vs. 10.1 months, respectively; p = .33) or OS (median, 16.6 vs. 18.7 months; p = .86) between the two maintenance regimens. Reintroduction of FOLFIRINOX was performed in 20.2% of patients, with a median PFS2 of 2.8 months (95% CI, 2.0–22.3). The rates of grade 3–4 toxicity were significantly higher with FOLFIRI maintenance CT than with 5FU (41% vs. 22%; p = .03), especially for neuropathy (73% vs. 9%). Conclusion 5FU monotherapy maintenance appeared to be as effective as FOLFIRI, in a FOLFIRINOX de-escalation strategy, which is largely used in France. Implications for Practice FOLFIRINOX de-escalation and maintenance is a feasible strategy in advanced pancreatic cancer that decreases chemotherapy toxicity to improve both survival and quality of life. Survivals in patients with maintenance therapy are clinically meaningful. Fluoropyrimidine monotherapy maintenance seems to be as efficient as FOLFIRI and should be a reference arm in future pancreatic cancer maintenance trials.

International audience; Fluoropyrimidine (FP) plus platinum chemotherapy has been recently established as a second-line (L2) preferred option in advanced biliary tract cancer (aBTC) (ABC-06 phase III trial). However, the overall survival (OS) benefit was limited and comparison with FP monotherapy was not available. Our aim was to assess the OS of patients treated with a FP monotherapy compared to a doublet with irinotecan or platinum in L2. We performed a retrospective analysis of two large multicenter prospective cohorts: a French cohort (28 centers) and an Italian cohort (9 centers). All consecutive patients with aBTC receiving FP-based L2 after gemcitabine plus cisplatin/gemcitabine plus oxaliplatin L1 between 2003 and 2016 were included. A subgroup analysis according to performance status (PS) and an exploratory analysis according to platinum sensitivity in L1 were planned. In the French cohort (n = 351), no significant OS difference was observed between the FP monotherapy and doublet groups (median OS: 5.6 vs 6.8 months, P = .65). Stratification on Eastern Cooperative Oncology Group (ECOG) PS showed similar results in PS 0-1 and 2. Median OS was not different between FP monotherapy, platinum- and irinotecan-based doublets (5.6 vs 7.1 vs 6.7 months, P = .68). Similar findings were observed in the Italian cohort (n = 174) and in the sensitivity analysis in pooled cohorts (n = 525). No L2 regimen seemed superior over others in the platinum resistant/refractory or sensitive subgroups. Our results suggest that FP monotherapy is as active as FP doublets in aBTC in L2, regardless of the patient PS and country, and could be a therapeutic option in this setting.

International audience; Hepatocellular carcinoma (HCC) and biliary tract cancers (BTC) display a poor prognosis with 5-year overall survival rates around 15%, all stages taken together. These primary liver malignancies are often diagnosed at advanced stages where therapeutic options are limited. Recently, immune therapy has opened new opportunities in oncology. Based on their high programmed death-ligand 1 expression and tumor-infiltrating lymphocytes, HCC and BTC are theoretically good candidates for immune checkpoint blockade. However, clinical activity of single agent immunotherapy appears limited to a subset of patients, which is still ill-defined, and combinations are under investigation. In this review, we provide an overview of (i) the biological rationale for immunotherapies in HCC and BTC, (ii) the current state of their clinical development, and (iii) the predictive value of immune signatures for both clinical outcome and response to these therapies.

BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy (L1) in advanced pancreatic ductal adenocarcinoma (aPDAC). FOLFOXIRI, a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil, has demonstrated efficacy and feasibility in colorectal cancer. AIM To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice. METHODS Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions, with either FOLFOXIRI (n = 165) or FOLFIRINOX (n = 124) regimens. FOLFOXIRI consisted of irinotecan (165 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2) and 5-fluorouracil (3200 mg/m2 as a 48-h continuous infusion) every 2 wk. Ninety-six pairs of patients were selected through propensity score matching, and clinical outcomes of the two treatment regimens were compared. RESULTS Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts, respectively. After propensity score matching, survival rates remained similar between the two regimens in terms of overall survival (hazard ratio = 1.22; P = 0.219) and progression-free survival (hazard ratio = 1.27; P = 0.120). The objective response rate was 37.1% in the FOLFOXIRI group vs 47.8% in the FOLFIRINOX group (P = 0.187). Grade 3/4 toxicities occurred in 28.7% of patients in the FOLFOXIRI cohort vs 19.5% in the FOLFIRINOX cohort (P = 0.079). FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events. Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5% with both regimens. CONCLUSION FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX. The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.

Resume Introduction La demographie des internes en oncologie a change depuis 2010 avec l’elargissement de l’effectif des promotions. L’evolution des aspirations des internes vis-a-vis de la recherche et de leur exercice futur en parallele de ces changements demographiques, n’a pas ete evaluee. Methodes Un questionnaire a ete elabore par le groupe jeune/translationnel Dig’IN du GERCOR (groupe cooperateur en oncologie), impliquant des cliniciens, des chercheurs, membres du GERCOR et des internes. Il comprenait 62 questions reparties en 7 sections : demographie, these de medecine, post-internat, mobilite, activite de recherche, recherche fondamentale et recherche clinique/translationnelle. L’enquete nationale a ete diffusee par l’Association d’enseignement et de recherche des internes en oncologie (AERIO). Resultats Au total, 143 internes ont participe, dont 116 (81,1 %) ayant complete le questionnaire dans son integralite. La population etait representative de la demographie actuelle avec une majorite de femmes (65,0 %) et un âge median de 28 ans. L’analyse non supervisee a revele quatre profils d’internes dont un profil tres interesse par la recherche, avec une volonte d’implication forte (16,8 %), un profil majoritaire avec volonte d’implication intermediaire (41,3 %) et un profil ne semblant pas du tout vouloir s’impliquer dans la recherche (14,7 %). L’incertitude quant a l’obtention d’un poste, le manque de temps et d’interactions avec les chercheurs apparaissaient comme les principales barrieres a l’implication dans la recherche. Conclusion Cette etude nationale a permis d’analyser plus finement le rapport des internes a la recherche academique. Elle pourra servir de base a la proposition de mesures adaptees a leurs attentes.

International audience; BACKGROUND:FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) is an option for fit patients with metastatic (MPC) and locally advanced unresectable (LAPC) pancreatic cancer. However, no criteria reliably identify patients with better outcomes.PATIENTS AND METHODS:We investigated putative prognostic factors among 137 MPC/LAPC patients treated with triplet chemotherapy. Association with 6-month survival status (primary endpoint) was assessed by multivariate logistic regression models. A nomogram predicting the risk of death at 6 months was built by assigning a numeric score to each identified variable, weighted on its level of association with survival. External validation was performed in an independent data set of 206 patients. The study was registered at ClinicalTrials.gov (NCT03590275).RESULTS:Four variables (performance status, liver metastases, baseline carbohydrate antigen 19-9 level, and neutrophil-to-lymphocyte ratio) were found to be associated with 6-month survival by multivariate analysis or had sufficient clinical plausibility to be included in the nomogram. Accuracy was confirmed in the validation cohort (C index = 0.762; 95% confidence interval, 0.713-0.825). After grouping all cases, 4 subsets with different outcomes were identified by 0, 1, 2, or > 2 poor prognostic features (P < .0001).CONCLUSION:The nomogram we constructed accurately predicts the risk of death in the first 6 months after initiation of FOLFIRINOX in MPC/LAPC patients. This tool could be useful to guide communication about prognosis, and to inform the design and interpretation of clinical trials.

Background: The management of locally advanced pancreatic cancer (LAPC) patients remains controversial. Better discrimination for overall survival (OS) at diagnosis is needed. We address this issue by developing and validating a prognostic nomogram and a score for OS in LAPC (PROLAP). Methods: Analyses were derived from 442 LAPC patients enrolled in the LAP07 trial. The prognostic ability of 30 baseline parameters was evaluated using univariate and multivariate Cox regression analyses. Performance assessment and internal validation of the final model were done with Harrell's C-index, calibration plot and bootstrap sample procedures. On the basis of the final model, a prognostic nomogram and a score were developed, and externally validated in 106 consecutive LAPC patients treated in Besançon Hospital, France. Results: Age, pain, tumour size, albumin and CA 19-9 were independent prognostic factors for OS. The final model had good calibration, acceptable discrimination (C-index=0.60) and robust internal validity. The PROLAP score has the potential to delineate three different prognosis groups with median OS of 15.4, 11.7 and 8.5 months (log-rank P, SCOPUS: ar.j, info:eu-repo/semantics/published

Docetaxel, cisplatin and 5-fluorouracil (DCF) chemotherapy regimen is highly effective in advanced anal squamous cell carcinoma (SCCA), as demonstrated by the Epitopes-HPV02 study results. Here, we analyzed the impact of DCF regimen and the prognostic value of adaptive immune responses and immunosuppressive cells in SCCA patients included in two prospective studies (Epitopes-HPV01 and HPV02). The presence of T-cell responses against Human papillomavirus (HPV)16-E6/E7 and anti-telomerase (hTERT)-antigens was measured by IFNᵧ-ELISpot. Here, we showed that HPV-adaptive immune responses are increased in SCCA patients. SCCA patients also displayed enhanced circulating TH1 T-cells restricted by hTERT. Exposition to DCF increased hTERT immunity but not HPV or common viruses immune responses. Notably, the correlation of hTERT immune responses with SCCA patients&rsquo, clinical outcomes highlights that hTERT is a relevant antigen in this HPV-related disease. The influence of peripheral immunosuppressive cells was investigated by flow cytometry. While both regulatory T-cells and monocytic-myeloid-derived suppressive cells (M-MDSC) accumulated in the peripheral blood of SCCA patients, only high levels of M-MDSC were negatively correlated with hTERT adaptive immune responses and predicted poor prognosis. Altogether, our results reveal that hTERT is a relevant antigen in HPV-driven SCCA disease and that M-MDSC levels influence TH1-adaptive immune responses and patients&rsquo, survival.

International audience; BACKGROUND:Enterocolitis is a rare, but serious gastrointestinal complication associated with docetaxel-based chemotherapy in patients with cancer. The incidence, clinical presentation and outcome of enterocolitis in patients with cancer treated with docetaxel-based chemotherapy was assessed in this study Patients and Methods: All patients treated with docetaxel for cancer between January 2010 and December 2014 at the University Hospital of Besançon were identified and their medical records reviewed.RESULTS:During this period, 1,227 patients received docetaxel chemotherapy and gastrointestinal events occurred in 381 (31.1%) patients. In multivariate analysis, a higher risk of gastrointestinal events was associated with a higher dose of docetaxel (≥75 mg/m2) (odds ratio(OR)=46.2; 95% confidence interval(CI)=5.4-397.0, p=0.0005) and the first cycle of docetaxel (OR=4.2; 95% CI=1.8-10.1, p=0.001). Among the 381 patients with gastrointestinal events, grade 3/4 neutropenia, diarrhea, febrile neutropenia, mucositis, nausea/vomiting, and rectal bleeding were diagnosed in 65 (17.1%), 51 (13.4%), 37 (9.7%); 12 (3.1%), seven (1.8%) and three (0.8%) patients, respectively; 54 patients (14.2%) were hospitalized. Computed tomographic scan was performed for 39 patients (10.2%). Twenty-seven patients presented radiological signs of enterocolitis. Three deaths (0.8%) related to enterocolitis were recorded. Docetaxel was resumed in 261 patients (68.5%) and the dose was reduced in 89 patients (23.4%). Docetaxel was discontinued in 120 patients (31.5%).CONCLUSION:Gastrointestinal events in patients treated with docetaxel may be a potential sign of fatal enterocolitis and require particular attention. Dose reduction at the first cycle may reduce the risk of such events.

Background Anal squamous cell carcinoma (SCCA) is associated with E6 and E7 oncoproteins encoded by human papillomavirus (HPV) 16. Addition of Docetaxel to 5-Fluorouracil plus Cisplatin (DCF) induces favorable disease control and complete remission rate in recent clinical trials. Taking this observation into account, we decided to analyze the impact of DCF chemotherapy on adaptive immunity and immunosuppressive cells in SCCA. Methods Peripheral blood mononuclear cells from healthy donors and SCCA patients included in Epitopes-HPV01 and 02 studies were analyzed. The presence of T-cell responses after short term T-cell stimulation against HPV16-E6/E7 and TERT-antigens was measured by IFNγ-ELISpot. Immune checkpoint expression and immunosuppressive cells were monitored by flow cytometry. Results We first observed an enhanced HPV-specific T-cell response following DCF chemotherapy. Our investigations also suggest that TERT might be a relevant antigen in HPV-driven cancers. TERT-restricted CD4 Th1 were correlated to E6 responses and also enhanced following DCF treatment of SCCA patients. The distribution of T-cell exhaustion markers on peripheral T lymphocytes unraveled a drop of CD226 expression and the emergence of CD226-TIGIT+ T-cell subset. Monocytic-myeloid-derived-suppressor cells (M-MDSC) and regulatory T-cell (Treg) rates were increased. Treg levels and T-cell exhaustion markers did not influence clinical outcomes and frequencies of specific immune responses. M-MDSC levels monitored after DCF chemotherapy were correlated with progression free survival and antigen-specific T-cell response intensity and diversity. Conclusions DCF chemotherapy did not impair antigen-specific T-cell responses, supporting the potential interest to combine DCF chemotherapy with immunotherapies. Moreover, our study identifies post-therapy M-MDSC as a prognostic factor in SCCA patients. Clinical trial identification Epitopes-HPV01: NCT01845779 Epitopes-HPV02: NCT02402842. Legal entity responsible for the study University Hospital of Besancon. Funding Besancon University Hospital, Ligue Contre le cancer Grand-Est and Association Nationale de la Recherche et de la Technologie. Disclosure All authors have declared no conflicts of interest.

Background FOLFIRINOX has shown promising results in LA or BR pancreatic adenocarcinoma (PA) in non-randomized series. We report here an updated large cohort of pts treated with FOLFIRINOX for a LA or BR PA. Methods This French retro-prospective multicenter study included all consecutive patients (pts), PS 0/1/2, with non-metastatic, non-resectable, non-pretreated, LA or BR PA treated with FOLFIRINOX. Non-resectability was defined by each center’s multidisciplinary team meeting at diagnosis according to the ISGPS guidelines. FOLFIRINOX chemotherapy (CT) was performed as described in the PRODIGE 4 trial until progression, major toxicity or consolidation treatment radiotherapy (RT) or surgery. Results At the time of database lock, in December 2018, 293 pts were included (42% female, 33% > 65 years, 97% PS Conclusions FOLFIRINOX for LA and BR PA seems to be effective with a manageable toxicity profile. However secondary surgery rate and OS were lower than what we previously reported, but similar to the meta-analysis we previously published. These promising results in “real life” pts have now to be confirmed in phase III randomized trial (PRODIGE 29 - NEOPAN). Updated results will be presented at the meeting. Legal entity responsible for the study AGEO. Funding Has not received any funding. Disclosure E. Francois: Advisory / Consultancy: Roche; Advisory / Consultancy: Servier; Advisory / Consultancy: Amgen; Advisory / Consultancy: MSD; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Novartis. J. Bachet: Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi. D. Tougeron: Advisory / Consultancy: Amgen; Advisory / Consultancy: Merck; Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche; Advisory / Consultancy: Bayer; Advisory / Consultancy: Servier. J. Forestier: Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bayer; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Ipsen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Honoraria (self): Servier. R. Coriat: Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy: Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Keocyt. J. Taieb: Advisory / Consultancy: Amgen; Advisory / Consultancy: Lily; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: MSD; Advisory / Consultancy: Celgene; Advisory / Consultancy: Servier; Advisory / Consultancy: Sirtex; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Amgen; Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.

Background Advanced pancreatic ductal adenocarcinoma (aPDAC) remains a challenging, non-curable disease. FOLFIRINOX regimen is the standard in first-line chemotherapy (L1) in this setting. FOLFOXIRI, a similar schedule with a lower dose of irinotecan and no bolus 5-fluorouracil, has demonstrated efficacy and good tolerance in metastatic colorectal cancer. We aimed to compare clinical outcomes of this two regimens in patients with aPDAC in routine clinical practice. Methods Analyses were derived from all consecutive aPDAC patients treated in L1, between 2011 and 2017 in two French institutions, with FOLFOXIRI (n = 165) or standard (n = 124) regimens. FOLFOXIRI consisted of irinotecan (165 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2) and 5-fluorouracil (3200 mg/m2 as a 48-hour continuous infusion) every two weeks. One hundred pairs of patients were selected through propensity score matching (PSM) analysis and clinical outcomes of the two treatments were compared. Results After a median follow up of 44.1 months, median overall survival (OS) was 11.1 months (95% confidence interval [CI], 9.8 to 13.1) in the FOLFOXIRI group and 11.6 months (95% CI, 10.8 to 15.5) in the FOLFIRINOX group. Median progression free survival (PFS) was 5.8 months (95% CI, 3.9 to 6.9) in the FOLFOXIRI group and 6.7 months (95% CI, 6.0 to 7.7) in the FOLFIRINOX group. After PSM, the survival of patients remained similar between the two regimens in OS (hazard ratio [HR], 0.79; 95% CI, 0.58 to 1.08; P = 0.137) and PFS (HR, 0.80; 95% CI, 0.60 to 1.08; P = 0.139). The objective response rate was 33.3% in the FOLFOXIRI group versus 47.2% in the FOLFIRINOX group, while disease-control rates were 62.8% and 75.3%, respectively (P = 0.129). The grade 3 or 4 toxicities were occurring in 29.0% of patients in FOLFOXIRI group versus 21.3% in FOLFIRINOX group (P = 0.216). FOLFOXIRI was associated with a higher incidence of grade 3 or 4 digestive adverse events compared to FOLFIRINOX group (11.0% versus 5.0%, respectively) but was similar to the safety profile of FOLFIRINOX previously reported in the PRODIGE 4/ACCORD 11 trial. Conclusions FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX regimen. Legal entity responsible for the study Besancon University Hospital. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.