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Background: Lymph node metastasis and positive resection margins have been reported to be major determinants of overall survival (OS) and poor recurrence-free survival (RFS) for patients who underwent resection for perihilar cholangiocarcinoma (pCCA). However, the prognostic value of positive lymph nodes independently from resection margin status on OS has not been evaluated. Methods: From the European Cholangiocarcinoma (ENSCCA) registry, patients who underwent resection for pCCA between 1994 and 2021 were included in this retrospective cohort study. The primary outcome was OS stratified for resection margin and lymph node status. The secondary outcome was recurrence-free survival. Results: A total of 325 patients from 11 different centers and six European countries were included. Of these, 194 (59.7%) patients had negative resection margins. In 113 (34.8%) patients, positive lymph nodes were found. Lymph node status, histological grade, and ECOG performance status were independent prognostic factors for survival. The median OS for N0R0, N0R1, N+R0, and N+R1 was 38, 30, 18, and 12 months, respectively (p < 0.001). Conclusion: These data indicate that in the presence of positive regional lymph nodes, resection margin status does not determine OS or RFS in patients with pCCA. Achieving negative margins in patients with positive nodes should not come at the expense of more extensive surgery and associated higher mortality. The ENSCCA Registry is completely funded by the European Association for the Study of the Liver (EASL; Registry grant awards 2016 and 2019 to J.M.B.), Incyte Bioscience International Sàrl (grant award 2020 to J.M.B.) and European Union’s Horizon 2020 Research and Innovation Program (grant number 825510, ESCALON: to J.M.B. and A.L.).

PURPOSEApproved systemic therapies for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have shown limited capacity to reduce tumor burden and no antitumor activity after progression to targeted agents (TAs). We investigated the efficacy and safety of lenvatinib in patients with previously treated advanced GEP-NETs.PATIENTS AND METHODSThis was a multicenter, single-arm, open-label, phase II trial with two parallel cohorts (ClinicalTrials.gov identifier: NCT02678780 ) involving 21 institutions in 4 European countries. Eligible patients had histologically confirmed advanced grade 1-2 pancreatic (panNET) or GI (GI-NET) NETs with documented tumor progression after treatment with a TA (panNET) or somatostatin analogs (GI-NET). Patients were treated with lenvatinib 24 mg once daily until disease progression or treatment intolerance. The primary end point was overall response rate by central radiology review. Secondary end points included progression-free survival, overall survival, duration of response, and safety.RESULTSBetween September 2015 and March 2017, a total of 111 patients were enrolled, with 55 (panNET) and 56 (GI-NET) patients in each cohort. The median follow-up was 23 months. The overall response rate was 29.9% (95% CI, 21.6 to 39.6): 44.2% (panNET) and 16.4% (GI-NET). The median (range) duration of response was 19.9 (8.4-30.8) and 33.9 (10.6-38.3) months in the panNET and GI-NET groups, respectively. The median progression-free survival was 15.7 months (95% CI, 14.1 to 19.5). The most common adverse events were fatigue, hypertension, and diarrhea; 93.7% of patients required dose reductions or interruptions.CONCLUSIONWe report the highest centrally confirmed response reported to date with a multikinase inhibitor in advanced GEP-NETs, with a particularly strong response in the panNET cohort. This study provides novel evidence for the efficacy of lenvatinib in patients with disease progression following treatment with other TAs, suggesting the potential value of lenvatinib in the treatment of advanced GEP-NETs.

Biliary tract cancers (BTCs) are a group of rare and aggressive malignancies that arise in the biliary tree within and outside the liver. Beyond surgical resection, which is beneficial for only a small proportion of patients, current strategies for treating patients with BTCs include chemotherapy, as a single agent or combination regimens, in the adjuvant and palliative setting. Increased characterisation of the molecular landscape of these tumours has facilitated the identification of molecular vulnerabilities, such as IDH mutations and FGFR fusions, that can be exploited for the treatment of BTC patients. Beyond targeted therapies, active research avenues explore the development of novel therapeutics that target the crosstalk between cancer and stroma, the cellular pathways involved in the regulation of cell death, the chemoresistance phenotype and the dysregulation of RNA. In this review, we discuss the therapeutic opportunities currently available in the management of BTC patients, and explore the strategies that can support the implementation of precision oncology in BTCs, including novel molecular targets, liquid biopsies and patient-derived predictive tools.

[Lessons Learned] - Palbociclib demonstrated no detectable activity in molecularly unselected and heavily pretreated patients with advanced grade 1/2 pancreatic neuroendocrine tumors. - Predictive biomarkers that improve patient selection should be investigated in future studies of palbociclib., [Background] Palbociclib, a CDK4/6 inhibitor, has shown in vitro activity in pancreatic neuroendocrine tumor (pNET) cell lines. Here we prospectively assessed the activity and safety of palbociclib in monotherapy in metastatic refractory pNETs., [Methods] This was a nonrandomized, open‐label, phase II study of patients with metastatic grade (G)1/2 pNETs recruited from 10 centers in Spain. Palbociclib 125 mg was orally administered once daily for 21 of 28 days until disease progression or unacceptable toxicity., [Results] Twenty‐one patients were included; 52.4% were men, and median age was 57.4 years (range, 37.4–73.4). Patients had previously received a median of three prior lines of systemic therapy (range, 1–10) for advanced disease (somatostatin analogues, 71.4%; sunitinib, 81.0%; everolimus, 47.6%; chemotherapy, 47.6%). Nineteen patients were evaluated for objective response rate (ORR), with a median follow‐up of 12.4 months (range, 7.53–19.33). No objective and confirmed responses were observed (0%); 11 (57.9%) patients had stable disease, and 6 of them lasted more than 6 months; 8 (42.1%) patients had disease progression as best response. Median progression‐free survival (PFS) was 2.6 months (95% confidence interval [CI], 0–14.4) and median overall survival (OS) was 18.7 months (95% CI, 7.4–29.9; Fig. 1). Most frequent toxicities of any grade were asthenia (76.2%), neutropenia (42.9%), diarrhea (33.3%), and nausea (33.3%). Five (23.8%) patients developed G3–4 neutropenia and two (9.5%) patients developed G3–4 thrombocytopenia., [Conclusion] Lack of activity was observed with palbociclib as a single agent in molecularly unselected and heavily pretreated patients with advanced G1/2 pNETs., This work was supported by Pfizer Oncology.

Most of the patients with cholangiocarcinoma (CCA) present with advanced (inoperable or metastatic) disease, and relapse rates are high in those undergoing potentially curative resection. Previous treatment nihilism of patients with advanced disease has been replaced by active clinical research with the advent of randomized clinical trials (RCTs) and a much greater effort at understanding molecular mechanisms underpinning CCA. Three RCTs have recently been reported evaluating adjuvant chemotherapy following curative resection; only one of these has the potential to change practice. The BILCAP study failed to meet its primary endpoint by intention-to-treat analysis; however, a survival benefit was seen in a preplanned sensitivity analysis (predominantly adjusting for lymph nodes status). This, along with the numerical difference in median overall survival has led to the uptake of adjuvant capecitabine by many clinicians. In patients with advanced disease, the only level 1 data available supports the use of cisplatin and gemcitabine for the first-line treatment of patients with advanced disease; there is no established second-line chemotherapy. Previous forays into targeted therapy have proven unfruitful (namely targeting the epithelial growth factor receptor and vascular endothelial growth factor pathways). An increasing number of genomic subtypes are being defined; for some of these on-target therapeutic options are under active investigation. The most developed are studies targeting IDH-1 (isocitrate dehydrogenase) mutations and FGFR-2 (fibroblast growth factor receptor) fusions, with promising early results. Several other pathways are under evaluation, along with early studies targeting the immune environment; these are too premature to change practice to date. These emerging treatments are discussed.

360 Background: Angiogenesis plays an important role in NET development and progression. Axitinib is a potent and selective VEGFR-1,2,3 inhibitor, with proven activity against several vascular-dependent solid tumors. The aim of this randomized, double-blind phase II/III study was to assess the efficacy of axitinib in patients with advanced G1-2 extra-pancreatic NETs. Methods: Eligible pts were randomized (1:1) to receive octreotide LAR (30 mg IM q4w) with axitinib (5 mg BID) or placebo BID until disease progression or unacceptable toxicity. Pteswere stratified by time from diagnosis to study entry ( > or < 12m), primary tumor site (GI tract vs non-GI) and Ki-67 index (< 5% vs > 5%). Prior therapy with SSA, IFN and up to 2 lines of systemic treatment was allowed, but not prior VEGF- or VEGFR-targeted drugs. Clinical and/or radiological disease progression within 12 months prior to study entry was required. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), time to progression, overall response rate (ORR), duration of response, biochemical response and safety. Results: 256 pts were randomized (106 in the Phase II part, and 150 additional pts in the Phase III part), 126 to axitinib and 130 to placebo. The main characteristics of the study population were: median age 61 years (range: 21-85), 52% male, PS 0-1 (64-35%), G1-2 (29%-71%), primary tumor site GI (40%)-Lung (17%)-Other (32%). Prior therapies included: SSA (46%), everolimus (13%), chemotherapy (13%), TACE (5%) and PRRT (2%). ORR was significantly higher in axitinib- vs placebo-treated patients (17.5% vs 3.8%, p = 0.0004). PFS per investigator assessment also favored axitinib vs placebo-treated patients, although the difference did not reach statistical significance (median PFS 17.2 vs 12.3 months, respectively, HR 0.816, p = 0.169). Grade 3-4 treatment-related AEs occurred more frequently in the axitinib vs placebo arm (52% vs 13.8%), and included hypertension (21% vs 6 %), cardiac disorders (3.2% vs 0.7%), diarrhoea (13% vs 1.5 %), asthenia (9% vs 3%) and nausea&vomiting (2% vs 0.7%). There were 3 treatment-related deaths, 1 in the axitinib arm (cardiac failure) and 2 in the placebo arm (myocardial infarction and hepatorenal syndrome). Conclusions: Although the study failed to demonstrate a significant PFS benefit per investigator assessment, axitinib in combination with octreotide LAR demonstrated activity and had a tolerable safety profile in patients with advanced G1-2 extra-pancreatic NETs. Data base cleaning and central blinded radiological PFS assessment are currently ongoing. Clinical trial information: NCT01744249.

Purpose Gemcitabine plus nanoparticle albumin-bound (NAB) paclitaxel (GA) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and a Karnofsky performance status (PS) of 70% or greater. Because of the low number of patients with reduced PS, the efficacy of this regimen in fragile patients remains unclear. This study aimed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS. Patients and Methods In the phase I part of this study, patients were randomly assigned to one of the following four parallel GA treatment arms (six patients per arm): a biweekly schedule of NAB-paclitaxel (150 mg/m2 [arm A] or 125 mg/m2 [arm C]) plus gemcitabine 1,000 mg/m2 or a standard schedule of 3 weeks on and 1 week off of NAB-paclitaxel (100 mg/m2 [arm B] or 125 mg/m2 [arm D]) plus gemcitabine 1,000 mg/m2. The two regimens with the better tolerability profile on the basis of predefined criteria were evaluated in the phase II part of the study, the primary end point of which was 6-month actuarial survival. Results Arms B and D were selected for the phase II part of the study. A total of 221 patients (111 patients in arm B and 110 patients in arm D) were enrolled. Baseline characteristics including median age (71 and 68 years in arms B and D, respectively), sex (51% and 55% men in arms B and D, respectively), and metastatic disease (88% and 84% in arms B and D, respectively) were comparable between arms. The most frequent grade 3 or 4 toxicities in arms B and D were anemia (12% and 7%, respectively), neutropenia (32% and 30%, respectively), thrombocytopenia (7% and 11%, respectively), asthenia (14% and 16%, respectively), and neurotoxicity (11% and 16%, respectively). In arms B and D, there were no significant differences in response rate (24% and 28%, respectively), median progression-free survival (5.7 and 6.7 months, respectively), and 6-month overall survival (63% and 69%, respectively). Conclusion NAB-paclitaxel administered at either 100 and 125 mg/m2 in combination with gemcitabine on days 1, 8, and 15 every 28 days is well tolerated and results in acceptable safety and efficacy in patients with metastatic pancreatic ductal adenocarcinoma and a poor PS.

3549 Background: The outcome for mCRC has changed since the introduction of new chemotherapy schedules and targeted therapies, however new predictive biomarkers are needed. bCTCs and BRAF / PIK3CA mutations have been studied as a potential predictive biomarkers. The primary endpoint was progression-free survival (PFS) in pts WT KRAS and 1) and mutation status of BRAF and/or PIK3CA (WT vs MUT) and randomized to group A (FOLFIRI+Bev) or group B (FOLFIRI+Cet). Results: 240 pts (196 WT and 44 MUT: 6 BRAF, 12 PIK3CA and 6 BRAF + PIK3CA) were included. General characteristics per mutation status (WT vs MUT): Mean age (59 vs 61 years), gender (Male/Female 68/32 vs 70/30%), ECOG 0/1 (57/43 vs 66/34%), primary tumor unresected (48 vs 64%), RAS MUT in 12 pts (11 and 1 pts, respectively), previous chemotherapy (12 vs 9%). Overall response rate (ORR) was 52 and 41% in the WT and MUT groups, respectively. PFS and overall survival (OS) are presented in the table. Conclusions: In the low risk mCRC pts according to bCTCs, BRAF and/or PIK3CA MUT have a negative impact in OS and a trend to worse PFS in the ITT population. The impact of treatment is under evaluation and will be provided during the meeting. Clinical trial information: 2012-000840-90. [Table: see text]

4106 Background: Approved systemic therapies for advanced NETs have showed limited tumor shrinkage and no data of activity after progression to prior targeted agents (TA) is available. Lenvatinib, a potent VEGFR1-3 & FGFR1-4 inhibitor may increase efficacy and revert primary and acquired resistance to TA. We report the final results of the TALENT trial. Methods: Two independent cohorts were included: panNETs and giNETs. All pts had baseline documented progression disease (PD) by RECIST. For panNETs, PD to TA was mandatory, regardless of prior therapy with somatostatin analogs (SSAs) or chemotherapy (CHT); and for giNETs, PD on SSAs. Pts were treated with lenvatinib at 24 mg qd until PD or intolerable toxicity. The primary endpoint was overall response rate (ORR) by central radiology review. Progression-free (PFS) and overall survival (OS) were assessed by investigator. With 55 pts per arm, our study was powered to identify an ORR ≥25% (90% power, 5% α-error). Results: We recruited 111 pts: 55 panNETs and 56 giNETs (78% from small intestine). Prior therapies were CHT 32%, SSAs 87%, everolimus 70% and sunitinib 30% for panNETs. ORR was 29%, 42.3% for panNETs and 16.3% for giNETs. With a median follow-up of 19 m, PFS and OS for panNETs were 15.5 m (95% CI 11.3-not reached (NR)) and 29.2 m (95% CI 23.2-NR); and 15.4 m (95% CI 11.5-19.4) and NR for giNETs, respectively. Pts who obtained a response by RECIST had a significantly better PFS compared with non-responders (NR vs 11.2 m in panNETs (p=0.004); 37.2 m vs 14.9 m in giNETs (p=0.005). In the subgroup analyses, all pts obtained the same benefit in PFS and ORR, including tumor grade, prior therapies, hormone release, primary location and tumor burden. The most frequent G3/4 adverse events were hypertension (22%), fatigue (11%) and diarrhea (11%). Dose reductions/interruptions were needed in 91.8% with a median dose of 20 mg qd. Conclusions: To our knowledge, we report the highest ORR by central radiology assessment with a TA in this setting. Lenvatinib showed a promising PFS and OS in a pretreated population with benefit across subgroups. Further development in advanced NETs is warranted. Clinical trial information: NCT02678780.

3507 Background: FOLFOXIRI+BEV has demonstrated a survival benefit compared with FOLFIRI plus BEV (TRIBE Lancet Oncol 2015) in first-line mCRC. Nevertheless, due to its safety profile, this schedule is not recommended for all pts. In addition, we have showed that the detection of ≥3 bCTCs is a poor prognostic factor for survival (MACRO The Oncologist 2012). The VISNU-1 trial compares FOLFOX + BEV vs FOLFOXIRI + BEV in pts with mCRC and ≥3 bCTCs. Progression-free survival (PFS) is the primary endpoint. Secondary endpoints included overall response rate (ORR) and overall survival (OS). Methods: This is an open, multicentric, randomized phase III trial. Patients with mCRC younger than 70 years, ECOG 0-1 were randomized to FOLFOX+BEV (arm A) or FOLFOXIRI+BEV (arm B), stratified per KRAS mutation (mutated vs WT) and number of involved organs (1 vs >1). Results: 349 pts were included in the ITT population; 177 in group A and 172 in group B. Characteristics of the pts, molecular profiling and safety analysis have been previously presented at ASCO 2018 and showed that this schedule had an acceptable toxicity profile. Efficacy analysis in the ITT population is shown in the table. Conclusions: In this population with very bad prognosis, our study met its primary endpoint. Pts who received FOLFOXIRI + Bev benefit for a statistically significative PFS and ORR. OS showed a trend of benefit in the experimental arm. According to these results, FOLFOXIRI-Bev could be considered an adequate treatment option for pts with mCRC and ≥3 bCTCs. Clinical trial information: 2012-000846-37. [Table: see text]

332 Background: Pts with advanced G1/G2 NETs have limited treatment options with overall response rates (ORR) with targeted agents (TA) < 10%. Benefit on PFS after TA therapy has not been demonstrated. The mechanism of action of lenvatinib (VEGFR1-3 & FGFR1-4 inhibitor) may increase efficacy and revert primary and acquired resistance to TA. We report the updated results on PFS, safety and subgroups. Methods: This prospective phase II study had two cohorts: G1/G2 panNETs and giNETs. All pts had baseline documented disease progression (PD) by RECIST. For panNETs, PD to TA was mandatory, regardless prior therapy with somatostatin analogs (SSAs) or chemotherapy (CHT), and for giNETs, PD on SSAs. Pts were treated with lenvatinib at 24 mg qd until PD or intolerable toxicity. The primary endpoint was ORR by central radiology review. PFS was calculated by investigator assessment. Biochemical responses were defined as reduction from baseline > 50%. With 55 pts per arm our study was powered to identify an ORR ≥ 25% (90% power, 5% α-error). Results: We recruited 111 pts (55 panNETs/56 giNETs). Prior therapies were CHT 32%, SSAs 87%, everolimus (E) 70% and sunitinib (S) 30% for panNETs. ORR was 29%, 40% for panNETs and 18.5% for giNETs. With a median follow-up of 17 months (m), PFS for panNETs was 15.8 m (95% CI 11.4-NR) and 15.4 m (95% CI 11.5-19.5) for giNETs. Dose reductions/interruptions were needed in 91.8% with a median dose of 20 mg qd. In the subgroups analyses, all pts obtained the same benefit in PFS and ORR, including grade and prior therapy with S (PFS: 16.4 m, ORR: 43.7%) or E (PFS: 15 m, ORR: 37.1%) (p = ns). A significant correlation of chromogranin A decrease and prolonged PFS in giNETs (17.6 m vs NR, p = 0.032) was observed. The most frequent G3-4 adverse events were hypertension (20.7%), asthenia (13.5%), diarrhea (7.2%) and abdominal pain (5.4%). Conclusions: Lenvatinib showed the highest reported ORR with a TA by central radiology assessment in panNETs and giNETs with promising PFS in a pretreated population. The benefit was observed across subgroups analyses, including pretreated pts with TA. Clinical trial information: NCT02678780.

The REDISSEC CARESS-CCR (Results and Health Services Research in Colorectal Cancer)- group: Jose María Quintana, Marisa Baré, Maximino Redondo, Eduardo Briones, Nerea Fernández de Larrea, Cristina Sarasqueta, Antonio Escobar, Francisco Rivas, Maria M. Morales-Suárez, Juan Antonio Blasco, Isabel del Cura, Inmaculada Arostegui, Amaia Bilbao, Nerea González, Susana García-Gutiérrez, Iratxe Lafuente, Urko Aguirre, Miren Orive, Josune Martin, Ane Antón-Ladislao, Núria Torà, Marina Pont, María Purificación Martínez del Prado, Alberto Loizate, Ignacio Zabalza, José Errasti, Antonio Z Gimeno, Santiago Lázaro, Mercè Comas, Jose María Enríquez, Carlos Placer, Amaia Perales, Iñaki Urkidi, Jose María Erro, Enrique Cormenzana, Adelaida Lacasta, Pep Piera Pibernat, Elena Campano, Ana Isabel Sotelo, Segundo Gómez-Abril, F. Medina-Cano, Julia Alcaide, Arturo Del Rey-Moreno, Manuel Jesús Alcántara, Rafael Campo, Alex Casalots, Carles Pericay, Maria José Gil, Miquel Pera, Pablo Collera, Josep Alfons Espinàs, Mercedes Martínez, Mireia Espallargues, Caridad Almazán, Paula Dujovne Lindenbaum, José María Fernández-Cebrián, Rocío Anula Fernández, Julio Ángel Mayol, Ramón Cantero, Héctor Guadalajara, María Heras, Damián García, Mariel Morey, Javier Mar., [Background] Colorectal cancers are one of the most common forms of malignancy worldwide. But two significant areas of research less studied deserve attention: health services use and development of patient stratification risk tools for these patients., [Methods] Design: a prospective multicenter cohort study with a follow up period of up to 5 years after surgical intervention. Participant centers: 22 hospitals representing six autonomous communities of Spain. Participants/Study population: Patients diagnosed with colorectal cancer that have undergone surgical intervention and have consented to participate in the study between June 2010 and December 2012. Variables collected include pre-intervention background, sociodemographic parameters, hospital admission records, biological and clinical parameters, treatment information, and outcomes up to 5 years after surgical intervention. Patients completed the following questionnaires prior to surgery and in the follow up period: EuroQol-5D, EORTC QLQ-C30 (The European Organization for Research and Treatment of Cancer quality of life questionnaire) and QLQ-CR29 (module for colorectal cancer), the Duke Functional Social Support Questionnaire, the Hospital Anxiety and Depression Scale, and the Barthel Index. The main endpoints of the study are mortality, tumor recurrence, major complications, readmissions, and changes in health-related quality of life at 30 days and at 1, 2, 3 and 5 years after surgical intervention. Statistical analysis: In relation to the different endpoints, predictive models will be used by means of multivariate logistic models, Cox or linear mixed-effects regression models. Simulation models for the prediction of discrete events in the long term will also be used, and an economic evaluation of different treatment strategies will be performed through the use of generalized linear models., [Discussion] The identification of potential risk factors for adverse events may help clinicians in the clinical decision making process. Also, the follow up by 5 years of this large cohort of patients may provide useful information to answer different health services research questions., [Trial registration] ClinicalTrials.gov Identifier: NCT02488161. Registration date: June 16, 2015., This work was supported in part by grants from the Fondo de Investigación Sanitaria (PS09/00314, PS09/00910, PS09/00746, PS09/00805, PI09/90460, PI09/90490, PI09/90397, PI09/90453, PI09/90441); Department of Health of the Basque Country (2010111098); KRONIKGUNE –Centro de Investigación en Cronicidad (KRONIK 11/006); and the European Regional Development Fund (ERDF).

Cetuximab and panitumumab are epidermal growth factor receptor (EGFR) inhibitors used in metastatic colorectal cancer (mCRC). Most patients develop a papulopustular rash that may predict tumor response to treatment. EGFR gene polymorphisms may also determine tumor response and appearance of skin rash. We hypothesized an association between EGFR gene polymorphisms, papulopustular rash and response to anticancer treatment. Four EGFR polymorphisms (-216, -191, CA-SSR, R521K) were analysed in 51 patients with mCRC receiving anti-EGFR. Severity of cutaneous rash and tumor response was measured following standard scales. We report an association between SNP-216 and tumor response (P = 0.003): no tumor progression occurred in TT genotype. Moreover, 92.3% of the responder patients developed skin rash, 62.9% of them presenting a grade ≥2 (P = 0.015). Thus, although underpowered, our preliminary data suggest that SNP-216 polymorphism of the EGFR gene could be useful in predicting tumor response and the appearance of severe skin rash might also be associated.

3536Background: FOLFOXIRI plus bevacizumab has demonstrated a survival benefit compared with FOLFIRI plus bevacizumab (TRIBE Lancet Oncol 2015) in first-line mCRC. This schedule is not routinely re...

751 Background: In the VELOUR trial, adding Z to FOLFIRI improves OS, PFS and RR in mCRC pts progressing after oxaliplatin ±biologic agents. The ASQoP trial (NCT01571284) was designed to gather safety and QoL data from mCRC in real-life setting. We report data collected by the Spanish investigators. Methods: ASQoP is single-arm, open-label trial evaluating safety and QoL of Z in mCRC pts as 2nd line. Eligible pts received Z (4mg/kg) q2wks on day 1/cycle, followed by FOLFIRI (dosing was at physician’s discretion) until disease progression, unacceptable toxicity, death, or investigator/pt decision. The EQ-5D was used for utility index (UI) measure and the EORTC QLQ-C30 as generic cancer instrument. QoL population consisted of pts completing the questionnaire at baseline and ≥1 assessment post-baseline and received ≥1 part of 1 dose of study treatment. Results: The safety population comprised 77 pts with ≥1 completed cycle of treatment. Grade (G)3/4 AEs were reported in 72.7% of pts (vs 83.5% in VELOUR), being G3 most commonly reported. There was no G4 hypertension, stomatitis, or proteinuria. G4 Diarrhea was found in 1.3% of pts. Mean baseline UI was 0.7 (95% CI, 0.63-0.78) in 51 pts, and remained relatively stable at cycles 3 (n=39) and 7 (n=24), with a mean (±SD) change from baseline of 0.03 (±0.26) and -0.06 (±0.35), respectively. Mean baseline global health status score was 63.1 (95% CI, 55.8-70.4) in 54 pts, and remained stable up to cycle 9 with a mean (±SD) change from baseline of 4.17 (±38). Conclusions: Thisanalysis has identified no new safety signals and suggests an acceptable toxicity profile with a relatively stable UI and QoL in Spanish mCRC pts in the real-life setting. [Table: see text]

Oxaliplatin has been approved for adjuvant treatment of colorectal cancer. Toxicity induced by oxaliplatin is moderate and manageable, but some isolated cases of severe pulmonary toxicity associated to oxaliplatin have been reported. Two fatal cases of interstitial pneumonitis rapidly evolving to pulmonary fibrosis are reported here.

e14656 Background: The RECIST criteria may be limited in assessing response to biologic agents such as bevacizumab (BVZ). Retrospective studies of patients (pts) with colorectal liver metastases (C...

The diagnosis of adenocarcinomas located in the pancreas head, i.e., distal cholangiocarcinoma (dCCA) and pancreatic ductal adenocarcinoma (PDAC), constitutes a clinical challenge because they share many symptoms, are not easily distinguishable using imaging techniques and accurate biomarkers are not available. Searching for biomarkers with potential usefulness in the differential diagnosis of these tumors, we have determined serum metabolomic profiles in healthy controls and patients with dCCA, PDAC or benign pancreatic diseases (BPD). Ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis was performed in serum samples from dCCA (n = 34), PDAC (n = 38), BPD (n = 42) and control (n = 25) individuals, divided into discovery and validation cohorts. This approach permitted 484 metabolites to be determined, mainly lipids and amino acids. The analysis of the results led to the proposal of a logistic regression model able to discriminate patients with dCCA and PDAC (AUC value of 0.888) based on the combination of serum levels of nine metabolites (acylcarnitine AC(16:0), ceramide Cer(d18:1/24:0), phosphatidylcholines PC(20:0/0:0) and PC(O-16:0/20:3), lysophosphatidylcholines PC(20:0/0:0) and PC(0:0/20:0), lysophosphatidylethanolamine PE(P-18:2/0:0), and sphingomyelins SM(d18:2/22:0) and SM(d18:2/23:0)) and CA 19-9. In conclusion, we propose a novel specific panel of serum metabolites that can help in the differential diagnosis of dCCA and PDAC. Further validation of their clinical usefulness in prospective studies is required. This study was supported by the Centro Internacional sobre el Envejecimiento, Spain (OLD-HEPAMARKER, 0348_CIE_6_E) co-financed with European Union ERDF funds; Carlos III Institute of Health, Spain (PI16/00598, PI16/01126, PI18/01075, PI19/00819) and Miguel Servet Program (CON14/00129) co-financed by European Regional Development Fund; Asociación Española Contra el Cancer, Spain (AECC-Cánceres raros 2017/2020); H2020 ESCALON project: H2020-SC1-BHC-2018-2020; Fundacion La Caixa (Hepacare Project); MCIU/AEI/FEDER, EU (SAF2017-87301-R); Severo Ochoa Excellence Accreditation (SEV-2016-0644). A. Sanchez-Martin and A. Lapitz were supported by pre-doctoral scholarships funded by the Ministry of Science, Innovation and Universities (FPU17/04027) and the Basque Government (PRE_2017_1_0345), respectively, and M.L. Gutiérrez is supported by the "Stop fuga de Cerebros" grant from ROCHE FARMA SA. This work was carried out in the framework of Working Group 5 of the COST Action CA18122, European Cholangiocarcinoma Network, EURO-CHOLANGIO-NET.