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Lurbinectedin is a synthetic marine-derived anticancer agent that acts as a selective inhibitor of oncogenic transcription. Lurbinectedin monotherapy (3·2 mg/mIn this phase 3, open-label, randomised study, adult patients aged 18 years or older with SCLC who relapsed after platinum-based chemotherapy were recruited from 135 hospitals across North America, South America, Europe, and the Middle East. Patients were randomly assigned (1:1) centrally by dynamic allocation to intravenous lurbinectedin 2·0 mg/mBetween Aug 30, 2016, and Aug 20, 2018, 613 patients were randomly assigned to lurbinectedin plus doxorubicin (n=307) or control (topotecan, n=127; CAV, n=179) and comprised the intention-to-treat population; safety endpoints were assessed in patients who had received any partial or complete study treatment infusions (lurbinectedin plus doxorubicin, n=303; control, n=289). After a median follow-up of 24·1 months (95% CI 21·7-26·3), 303 patients in the lurbinectedin plus doxorubicin group and 289 patients in the control group had discontinued study treatment; progressive disease was the most common reason for discontinuation (213 [70%] patients in the lurbinectedin plus doxorubicin group vs 152 [53%] in the control group). Median overall survival was 8·6 months (95% CI 7·1-9·4) in the lurbinectedin plus doxorubicin group versus 7·6 months (6·6-8·2) in the control group (stratified log-rank p=0·90; hazard ratio 0·97 [95% CI 0·82-1·15], p=0·70). 12 patients died because of treatment-related adverse events: two (1%) of 303 in the lurbinectedin plus doxorubicin group and ten (3%) of 289 in the control group. 296 (98%) of 303 patients in the lurbinectedin plus doxorubicin group had treatment-emergent adverse events compared with 284 (98%) of 289 patients in the control group; treatment-related adverse events occurred in 268 (88%) patients in the lurbinectedin plus doxorubicin group and 266 (92%) patients in the control group. Grade 3 or worse haematological adverse events were less frequent in the lurbinectedin plus doxorubicin group than the control group (anaemia, 57 [19%] of 302 patients in the lurbinectedin plus doxorubicin group vs 110 [38%] of 288 in the control group; neutropenia, 112 [37%] vs 200 [69%]; thrombocytopenia, 42 [14%] vs 90 [31%]). The frequency of treatment-related adverse events leading to treatment discontinuation was lower in the lurbinectedin plus doxorubicin group than in the control group (26 [9%] of 303 patients in the lurbinectedin plus doxorubicin group vs 47 [16%] of 289 in the control group).Combination therapy with lurbinectedin plus doxorubicin did not improve overall survival versus control in patients with relapsed SCLC. However, lurbinectedin plus doxorubicin showed a favourable haematological safety profile compared with control.PharmaMar.

Summary Background Few options exist for treatment of patients with small-cell lung cancer (SCLC) after failure of first-line therapy. Lurbinectedin is a selective inhibitor of oncogenic transcription. In this phase 2 study, we evaluated the acti and safety of lurbinectedin in patients with SCLC after failure of platinum-based chemotherapy. Methods In this single-arm, open-label, phase 2 basket trial, we recruited patients from 26 hospitals in six European countries and the USA. Adults (aged ≥18 years) with a pathologically proven diagnosis of SCLC, Eastern Cooperative Oncology Group performance status of 2 or lower, measurable disease as per Response Criteria in Solid Tumors (RECIST) version 1.1, absence of brain metastasis, adequate organ function, and pre-treated with only one previous chemotherapy-containing line of treatment (minimum 3 weeks before study initiation) were eligible. Treatment consisted of 3·2 mg/m2 lurbinectedin administered as a 1-h intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. The primary outcome was the proportion of patients with an overall response (complete or partial response) as assessed by the investigators according to RECIST 1.1. All treated patients were analysed for activity and safety. This study is ongoing and is registered with ClinicalTrials.gov , NCT02454972 . Findings Between Oct 16, 2015, and Jan 15, 2019, 105 patients were enrolled and treated with lurbinectedin. Median follow-up was 17·1 months (IQR 6·5–25·3). Overall response by investigator assessment was seen in 37 patients (35·2%; 95% CI 26·2–45·2). The most common grade 3–4 adverse events (irrespective of causality) were haematological abnormalities—namely, anaemia (in nine [9%] patients), leucopenia (30 [29%]), neutropenia (48 [46%]), and thrombocytopenia (seven [7%]). Serious treatment-related adverse events occurred in 11 (10%) patients, of which neutropenia and febrile neutropenia were the most common (five [5%] patients for each). No treatment-related deaths were reported. Interpretation Lurbinectedin was active as second-line therapy for SCLC in terms of overall response and had an acceptable and manageable safety profile. Lurbinectedin could represent a potential new treatment for patients with SCLC, who have few options especially in the event of a relapse, and is being investigated in combination with doxorubicin as second-line therapy in a randomised phase 3 trial. Funding Pharma Mar.

Objective: Long-term survivors (LS) of non-small cell lung cancer (NSCLC) without driver alterations, displaying an overall survival (OS) of more than 3 years, comprise around 10% of cases in several series treated with chemotherapy. There are classical prognosis factors for these cases [stage, Eastern Cooperative Oncology Group (ECOG), etc.], but more data are required in the literature. In this multi-center study, we focused on LS of advanced NSCLC with OS above 36 months to perform a clinical-pathological and molecular characterization. Methods: In the first step, we conducted a clinical-pathological characterization of the patients. Afterwards, we carried out a genetic analysis by comparing LS to a sample of short-term survivors (SS) (with an OS less than 9 months). We initially used whole-genome RNA-seq to identify differentiating profiles of LS and SS, and later confirmed these with reverse transcription-polymerase chain reaction (RT-PCR) for the rest of the samples. Results: A total of 94 patients were included, who were mainly men, former smokers, having adenocarcinoma (AC)-type NSCLC with an ECOG of 0–1. We obtained an initial differential transcriptome expression, displaying 5 over- and 33 under-expressed genes involved in different pathways: namely, the secretin receptor, surfactant protein, trefoil factor 1 (TFF1), serpin, Ca-channels, and Toll-like receptor (TLRs) families. Finally, RT-PCR analysis of 40 (20 LS/20 SS) samples confirmed that four genes (surfactant proteins and SFTP) were significantly down-regulated in SS compared to LS by using an analysis of covariance (ANCOVA) model: SFTPA1 (P = 0.023), SFTPA2 (P = 0.027), SFTPB (P = 0.02), and SFTPC (P = 0.047). Conclusions: We present a sequential genetic analysis of a sample of NSCLC LS with no driver alterations, obtaining a differential RNA-seq/RT-PCR profile showing an abnormal expression of SF genes.

BackgroundCurrent front-line treatment for ES-SCLC includes chemotherapy plus a PD-L1 inhibitor. FDA has recently approved LUR for pretreated patients with SCLC. 2SMALL is a two-part phase 1/2 study assessing the safety, tolerability and efficacy of LUR in combination with ATZ as second line treatment for ES-SCLC. Here we report data from phase I part of the 2SMALL trial (data cut off 14-07-2021)Methods2SMALL phase I was an open-label, single arm, dose exploration trial. Elegible patients had confirmed ES-SCLC, who progressed to first line platinum based treatment, ECOG performance status score 0-1 and adequate organ function; prior exposure to immunotherapy was not allowed. During dose finding phase pts received increasing doses of LUR (2.5 mg/m2 - 3.2 mg/m2) on day (D) 1 plus a fixed dose of ATZ (1200 mg) every 3 weeks following a standard 3+3 dose escalation design. Study endpoints included the definition of the safety profile and the recommended dose. Additional objectives included efficacy (ORR and PFS).Results26 patients were treated, including male 14 pts (53,84%), with median age 60.6 years. Five pts received LUR 2.5 mg/m2 + ATZ 1200 mg, and 3 pts were evaluable without DLT. Out of the 21 pts who received LUR 3.2 mg/m2+ ATZ 1200 mg (6 pts with primary G-CSF), 5 pts (20.83%) developed DTLs: 2 pts G3 febrile neutropenia (9.52%) (1 pt with G4 thrombocytopenia), 2 pts G4 neutropenia lasting more than 72h (9.52%), 1 pt G4 thrombocytopenia (4.76%). Most frequent haematological adverse events ≥ grade 2 (21 pts) were neutropenia (42.86%), thrombocytopenia (28.57%), anaemia (19.05%); lymphopenia (4.76%) and febrile neutropenia (4.76%). The most common non-haematological TAEs ≥ grade 2 was asthenia 30,76%. No deaths treatment-related were reported. Objective responses were observed in 15 pts (ORR: 57.69%), including complete responses in 2 pts (7.69%), partial response in 13 pts (50%). 6 pts had stable disease (26.92%) and 3 pts progressive disease (11.54%). Disease control rate was 84.61%. With 8 pts censored for progression, median PFS was 4.93 months (range 3.37 - 7.67 months).ConclusionsThe combination of LUR plus ATZ was well tolerated, without unexpected toxicities. Transient haematological toxicity was dose limiting. The RD for further studies is LUR 3.2 mg/m2 on D1 + ATZ 1200 mg D1 with G-CSF. Preliminary anti-tumor activity is remarkable. 2SMALL trial part II is ongoing, and will provide further data regarding efficacy and safety of the regimen for second line SCLC.Trial RegistrationNCT04253145ReferencesSubbiah V, Paz-Ares L, Besse B, et al. Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment. Lung Cancer 2020;150:90–96.Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol 2020; 21(5):645–654.Ethics ApprovalEthics committe Hospital Universitario 12 de Octubre

Sarcomatoid carcinoma is a subtype of non-small cell lung cancer (NSCLC) characterized by mesenchymal – epithelial transition component and awful prognosis. In this report, based on a case of stage IV lung sarcomatoid carcinoma with an extraordinary evolution and survival over 4 years, we address unresolved questions about the treatment of this cancer. We also make a literature review about the key factors that characterize this histology and that should be considered when treating those patients. Sarcomatoid carcinoma presents with mutations as KRAS, EGFR, ALK or MET in up to 70% of cases, and an important expression of PD-L1 (also called B7-H1), which can influence treatment of those patients with new drugs as immune checkpoint inhibitors. Immunotherapy has changed the horizon of patients with stage IV lung cancers without driver mutations, as their survival has improved extraordinary. Moreover, radical treatments are being considered in long survivors with oligometastatic disease. In this report, we review targeted and radical therapy, treatment duration and the mechanisms responsible of disease evolution of sarcomatoid tumors., Highlights • Sarcomatoid lung cancer is a rare entity with awful prognosis. • It may express driver mutations for potential treatment of those patients. • There are arising data of efficacy of immunotherapy in sarcomatoid lung carcinoma.

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SummaryBackground A phase I study found remarkable activity and manageable toxicity for doxorubicin (bolus) plus lurbinectedin (1-h intravenous [i.v.] infusion) on Day 1 every three weeks (q3wk) as second-line therapy in relapsed small cell lung cancer (SCLC). An expansion cohort further evaluated this combination. Patients and methods Twenty-eight patients with relapsed SCLC after no more than one line of cytotoxic-containing chemotherapy were treated: 18 (64%) with sensitive disease (chemotherapy-free interval [CTFI] ≥90 days) and ten (36%) with resistant disease (CTFI Results Ten patients showed confirmed response (overall response rate [ORR] = 36%); median progression-free survival (PFS) = 3.3 months; median overall survival (OS) = 7.9 months. ORR was 50% in sensitive disease (median PFS = 5.7 months; median OS = 11.5 months) and 10% in resistant disease (median PFS = 1.3 months; median OS = 4.6 months). The main toxicity was transient and reversible myelosuppression. Treatment-related non-hematological events (fatigue, nausea, decreased appetite, vomiting, alopecia) were mostly mild or moderate. Conclusion Doxorubicin 40 mg/m2 and lurbinectedin 2.0 mg/m2 on Day 1 q3wk has shown noteworthy activity in relapsed SCLC and a manageable safety profile. The combination is being evaluated as second-line therapy for SCLC in an ongoing, randomized phase III trial. Clinical trial registrationwww.ClinicalTrials.gov code: NCT01970540. Date of registration: 22 October, 2013.

Introduction: Based on the high incidence of thromboembolic events (TEs) observed in lung adenocarcinomas with ALK translocations and taking into account the biological proximity of ROS1 and ALK, we conducted a retrospective analysis of patients with advanced lung carcinoma carrying rearrangements in ROS1 from 23 centres in Spain and one centre in Portugal. Methods: The main objective of the study was to analyse the incidence of TE in this population, looking for predictive risk factors, and its impact on overall survival. Results: A total of 58 patients were included. The incidence of TEs throughout the disease was 46.6% (n = 27) with a median follow-up of 19 months (range: 1-78 months) and a median overall survival of 52 months in the total population and 50 months for the patients presenting TEs, with a hazards ratio of 1.12 (95% confidence interval: 0.47-2.65) p = 0.78. The majority of the events were venous (n = 24; 89%) and occurred in the ambulatory setting (n = 18; 67%). Almost half of the patients (n = 13; 48%) presented the TE in the peri-diagnostic period. Conclusions: The high incidence of thrombosis, especially during the cancer diagnosis process, requires special attention from a clinician. Despite the limitations of such a small descriptive study, its results are in accordance with previously reported data. It would be important to design prospective studies of antithrombotic prophylaxis in this population because of their possible impact in reducing the risk of TEs. (C) 2020 Elsevier Ltd. All rights reserved.

Introduction: The National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)≥180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m2 1 -h intravenous infusion every 3 weeks as second-line therapy. We report results for the pre-planned subset of patients with CTFI ≥ 180 days. Material and Methods: Twenty patients aged ≥18 years with pathologically proven SCLC diagnosis, pretreated with only one prior platinum-containing line, no CNS metastases, and with CTFI ≥ 180 days were evaluated. The primary efficacy endpoint was the overall response rate (ORR) assessed by the Investigators according to RECIST v1.1. Results: ORR was 60.0 % (95 %CI, 36.1−86.9), with a median duration of response of 5.5 months (95 %CI, 2.9−11.2) and disease control rate of 95.0 % (95 %CI, 75.1−99.9). Median progression-free survival was 4.6 months (95 %CI, 2.6−7.3). With a censoring of 55.0 %, the median overall survival was 16.2 months (95 %CI, 9.6-upper level not reached). Of note, 60.9 % and 27.1 % of patients were alive at 1 and 2 years, respectively. The most common grade 3/4 adverse events and laboratory abnormalities were hematological disorders (neutropenia, 55.0 %; anemia; 10.0 % thrombocytopenia, 10.0 %), fatigue (10.0 %) and increased liver function tests (GGT, 10 %; ALT and AP, 5.0 % each). No febrile neutropenia was reported. Conclusion: Lurbinectedin is an effective treatment for platinum-sensitive relapsed SCLC, especially in patients with CTFI ≥ 180 days, with acceptable safety and tolerability. These encouraging results suggest that lurbinectedin can be another valuable therapeutic option rather than platinum re-challenge., SCOPUS: ar.j, info:eu-repo/semantics/published

Objectives Neurotrophic tropomyosin receptor kinase (NTRK) fusions might be an off-target resistance mechanism to ALK Tyrosine Kinase Inhibitors (TKIs) in the same way as it has been suggested with activating epidermal growth factor receptor (EGFR) TKIs. Materials and methods DNA and RNA next-generation sequencing (NGS) was performed on the resected brain metastasis of a patient with advanced ALK Rearranged Non–Small Cell Lung Carcinoma (NSCLC) after resistance to several ALK TKIs including third generation ALK inhibitor, for pathological diagnosis and molecular resistance mechanism analysis. Results and conclusion NGS revealed an EML4-NTRK3 fusion that was confirmed by Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH). Despite having two potential targetable fusions, the patient did not respond to entrectinib, a multi-targeted pan-RTK, ROS1 and ALK inhibitor. NGS analysis in blood or tissues samples should be encouraged once resistance develops to TKIs in patients with ALK rearrangements, as actionable fusions, mutations or amplifications might arise as resistance mechanism and some patients could benefit from targeted therapy.

Resumen Introduccion y objetivos El sindrome de lisis tumoral (SLT) es una complicacion poco frecuente en neoplasias solidas tras el inicio de tratamiento, y su desarrollo espontaneo (SLTE) es excepcional. En este estudio se analizan las principales caracteristicas clinicas y pronosticas de una serie de casos con SLT y SLTE. Material y metodos Estudio retrospectivo observacional que incluyo a todos los pacientes con neoplasias solidas diagnosticados de SLT y SLTE en nuestro hospital en un periodo de 16 anos, siguiendo los criterios de Cairo-Bishop. Resultados Se incluyeron 19 pacientes (edad media 63 ± 16 anos): 10 pacientes (53%) presentaban SLT y 9 (47%) SLTE. En 8 casos (42%) el tumor primario fue de pulmon. Todos los pacientes presentaban deterioro grave de funcion renal en el momento del diagnostico, asociandose con hiperuricemia (16 ± 6 mg/dl) e hiperpotasemia (6 ± 0,9 mmol/l). A pesar del tratamiento con sueroterapia, alcalinizacion y rasburicasa, 3 pacientes (16%) requirieron tratamiento dialitico y 12 (63%) acabaron falleciendo durante el ingreso. Conclusiones El desarrollo de SLT en neoplasias solidas se asocia a una elevada mortalidad, por lo que es necesario un alto indice de sospecha para el diagnostico e inicio precoz de tratamiento.

Introduction and objective Tumour lysis syndrome (TLS) is an uncommon complication in solid tumours following treatment initiation, and its spontaneous development (STLS) is exceptional. In this study, we analyse the main clinical and prognostic features of a case series with TLS and STLS. Material and methods Observational retrospective study in which we included all patients with solid tumours diagnosed with TLS and STLS over a period of 16 years, according to Cairo-Bishop criteria. Results Nineteen patients were included in the study (mean age 63 ± 16 years): 10 patients (53%) with TLS, and 9 (47%) STLS. The primary tumour in 8 cases (42%) was lung cancer. All patients had severe renal impairment at the time of diagnosis along with hyperuricemia (16 ± 6 mg/dl) and hyperkalemia (6 ± 0.9 mmol/l). Despite treatment with intravenous fluids, urinary alkalinisation and rasburicase, 3 patients (16%) required dialysis, and 12 (63%) died during the follow-up period. Conclusions The development of TLS in solid tumours is associated with increased mortality and therefore, a high index of suspicion is essential for early diagnosis and treatment initiation.

Resumen La Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), a traves de las areas de Cirugia Toracica y de Oncologia Toracica, ha promovido la realizacion de un manual de recomendaciones para el diagnostico y el tratamiento del cancer de pulmon de celulas no pequenas. Las elevadas incidencia y mortalidad de esta patologia hacen necesaria una constante actualizacion de las mejores evidencias cientificas para su consulta por parte de los profesionales de la salud. Para su confeccion se ha contado con un amplio grupo de profesionales de distintas especialidades que han elaborado una revision integral, que se ha concretado en 4 apartados principales. En el primero se ha estudiado la prevencion y el cribado de la enfermedad, incluyendo los factores de riesgo, el papel de la deshabituacion tabaquica y el diagnostico precoz mediante programas de cribado. En un segundo apartado se ha analizado la presentacion clinica, los estudios de imagen y el riesgo quirurgico, incluyendo el cardiologico y la evaluacion funcional respiratoria. Un tercero trata sobre los estudios de confirmacion cito-histologica y de estadificacion, con un analisis de las clasificaciones TNM e histologica, metodos no invasivos y minimamente invasivos, asi como las tecnicas quirurgicas para el diagnostico y estadificacion. En un cuarto y ultimo capitulo se han abordado aspectos del tratamiento, como el papel de las tecnicas quirurgicas, la quimioterapia, la radioterapia, el abordaje multidisciplinar por estadios y otros tratamientos dirigidos frente a dianas especificas, terminando con recomendaciones acerca del seguimiento del cancer de pulmon y los tratamientos paliativos quirurgicos y endoscopicos en estadios avanzados.

Tumor lysis syndrome (TLS) is a life-threatening condition characterized by massive lysis of malignant cells after treatment, which results in hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. These metabolic abnormalities may cause acute kidney injury (AKI), seizures, cardiac arrhythmia and sudden death. Spontaneous TLS (STLS), which occurs in the absence of chemotherapy or radiotherapy, is a rare entity that has particularly been described in the setting of hematological malignancies. STLS has been exceptionally associated with solid tumors; however it could be an underdiagnosed entity and should certainly be considered in the differential diagnosis of AKI in patients with solid tumors. Moreover, due to further delay in diagnosis this entity could be associated with worse prognosis. Early management with intravenous hydration, hypouricemic agents and correction of electrolyte disorders are essential, although clinical course may be aggressive. We describe two unusual cases of STLS in the setting of small cell lung cancer who developed STLS. A high index of suspicion is needed in order to initiate necessary prophylactic precautions and avoid fatal consequences.

High incidence and prognostic relevance of thromboembolic disease in patients with ALK-rearranged NSCLCs

KRAS mutations represent one of the most prevalent oncogenic driver mutations in non-small cell lung cancer (NSCLC). For many years we have unsuccessfully addressed KRAS mutation as a unique disease. The recent widespread use of comprehensive genomic profiling has identified different subgroups with prognostic implications. Moreover, recent data recognizing the distinct biology and therapeutic vulnerabilities of different KRAS subgroups have allowed us to explore different treatment approaches. Small molecules that selectively inhibit KRAS G12C or use of immune checkpoint inhibitors based on co-mutation status are some examples which anticipate that personalized treatment for this challenging disease is finally on the horizon.

8506 Background: Lurbinectedin (L) is a novel anticancer drug that inhibits activated transcription and induces DNA double-strand breaks, leading to apoptosis. Methods: A multicenter phase 2 basket trial assessed the efficacy and safety of L in several cancer types, including small cell lung cancer (SCLC). Primary endpoint was confirmed overall response rate (ORR) by RECIST v.1.1. In the SCLC cohort, a target ORR ≥30% was set. One-hundred and five patients (pts) with ECOG PS 0-2 who had received one prior chemotherapy line were treated with L 3.2 mg/m2 as a 1-hour i.v. infusion on Day 1 q3wk. Results: Median age was 60 years (range, 40-83), 60% were male, ECOG PS 0/1/2 (32%/62%/6%), liver metastasis 41%, history of CNS involvement 3.8%, prior platinum 100%, median chemotherapy-free interval (CTFI): 3.5 (0-16.1) months; prior immunotherapy (IO): 7.6%. Pts received a median of 4 cycles (range, 1-24). Conclusions: L monotherapy is active in second-line SCLC in both resistant and sensitive disease. The acceptable and manageable safety profile is also associated to a convenient treatment administration (Day 1 q3wk). L as second-line treatment in SCLC emerges as a new promising drug for this unmet clinical need. Clinical trial information: NCT02454972. [Table: see text]

e20621 Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but more information is missing in the literature. Recently, EGFR, ALK and ROS 1 population (less than 20%) reach OS longer than 2 years. Immunotherapy has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 7 hospitals in Madrid. Methods: In this serie, first of all, we will try to make a clinical, histopathological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months). Initially, we used a NGS method of RNA-seq technology to identify differentiating profiles of gene expression between the two opposite populations. And finally, we confirmed this preliminary profile by RT-PCR in the rest of samples. Results: Ninety-six patients were initially included. The majority were men, smokers or former with adenocarcinoma and ECOG 0- 1. We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 over-expressed and 42 down-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this initial profile belong to different cellular pathways: Secretin Receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca-bindings Protein channel and Toll like Receptor family. Finally, we carried on by RT-PCR in 40 samples of SS and LS survivors and only four genes were significantly down-regulated in SS compared to LS in the multivariate analysis. These 4 genes were related to Surfactant Proteins: SFTPA1 (p = 0.023), SFTPA2 (p = 0.027), SFTPB (p = 0.02) and SFTPC (p = 0.047). Conclusions: We present a sequential genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA seq- and RT-PCR gene profile based on different surfactant proteins expression. A further confirmation in a larger sample is ongoing.

116 Background: NSCLC accounts for ~85% of lung cancers; most patients (pts) are at an advanced stage at the time of diagnosis. Cemiplimab (REGN2810) is being investigated for the treatment of NSCLC, in addition to other indications (NCT02383212). Methods: In the dose escalation (DE) phase, enrolled pts with advanced malignancies with no alternative standard-of-care therapeutic option received cemiplimab 1, 3 or 10 mg/kg every 2 weeks (Q2W) intravenously (IV) for up to 48 weeks. In the NSCLC expansion cohort (EC 1), enrolled pts with advanced disease who had relapsed after, or were refractory to at least first-line therapy received cemiplimab 200 mg Q2W IV for up to 48 weeks. Tumor biopsies were performed at baseline (EC 1 only), Day 29 and progression, if possible. Tumor measurements were performed every 8 weeks according to RECIST 1.1. Results: As of Sept 1, 2017, 21 pts with NSCLC (1 in DE at 1 mg/kg; 20 in EC 1) were enrolled; median age was 65.0 years (range, 50–82; 14 M/ 7 F); 81.0% had a ECOG performance status of 1, 19.0% of 0; 13/21 (61.9%) had a histology of adenocarcinoma. The most common treatment-related adverse events (TRAEs) were asthenia, pneumonitis, and rash (each n = 3, 14.3%). Each of the following ≥Grade 3 TRAEs occurred once: pneumonitis, diabetic ketoacidosis, and nephritis. By central independent review, 6 pts had partial response (PR), 6 had stable disease (SD) or non-complete response (CR)/non-progressive disease (PD), and 9 had PD. Overall response rate (ORR; CR + PR) was 28.6%. Duration of response exceeded 8 months in 5 of the 6 responders. Disease control rate (ORR + SD) was 57.1%. Disease control has been maintained for 7 pts after a planned treatment completion at 48 weeks. Of the 17 pts who had tissue available for PD-L1 expression evaluation, 11 (64.7%) had a tumor proportion score (TPS) of < 1%, and 3 (17.6) had a TPS of > 50%. Conclusions: Cemiplimab showed an acceptable safety profile and demonstrated antitumor activity in pretreated pts with NSCLC. Pivotal trials of cemiplimab as monotherapy or in combination with other treatments in pts with advanced NSCLC are currently enrolling (NCT03088540; NCT03409614). Clinical trial information: NCT02383212.

The Thoracic Surgery and Thoracic Oncology groups of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) have backed the publication of a handbook on recommendations for the diagnosis and treatment of non-small cell lung cancer. Due to the high incidence and mortality of this disease, the best scientific evidence must be constantly updated and made available for consultation by healthcare professionals.To draw up these recommendations, we called on a wide-ranging group of experts from the different specialties, who have prepared a comprehensive review, divided into 4 main sections. The first addresses disease prevention and screening, including risk factors, the role of smoking cessation, and screening programs for early diagnosis. The second section analyzes clinical presentation, imaging studies, and surgical risk, including cardiological risk and the evaluation of respiratory function. The third section addresses cytohistological confirmation and staging studies, and scrutinizes the TNM and histological classifications, non-invasive and minimally invasive sampling methods, and surgical techniques for diagnosis and staging. The fourth and final section looks at different therapeutic aspects, such as the role of surgery, chemotherapy, radiation therapy, a multidisciplinary approach according to disease stage, and other specifically targeted treatments, concluding with recommendations on the follow-up of lung cancer patients and surgical and endoscopic palliative interventions in advanced stages. (C) 2016 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved.

Tumour lysis syndrome (TLS) is an uncommon complication in solid tumors following treatment initiation, and its spontaneous development (STLS) is exceptional. In this study, we analyse the main clinical and prognostic features of a case series with TLS and STLS.Observational retrospective study in which we included all patients with solid tumours diagnosed with TLS and STLS over a period of 16 years, according to Cairo-Bishop criteria.Nineteen patients were included in the study (mean age 63±16 years): 10 patients (53%) with TLS, and 9 (47%) STLS. The primary tumour in 8 cases (42%) was lung cancer. All patients had severe renal impairment at the time of diagnosis along with hyperuricemia (16±6mg/dl) and hyperkalemia (6±0.9mmol/l). Despite treatment with intravenous fluids, urinary alkalinisation and rasburicase, 3 patients (16%) required dialysis, and 12 (63%) died during the follow-up period.The development of TLS in solid tumors is associated with increased mortality and therefore, a high index of suspicion is essential for early diagnosis and treatment initiation.

e21057Background: NSCLC accounts for ~85% of lung cancers; most patients (pts) are at an advanced stage at the time of diagnosis. Cemiplimab (REGN2810) is being investigated for the treatment of NS...

e21128Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors ...

17 Background: Patients diagnosed with gastroesophageal adenocarcinoma (GEA) have a poor prognosis despite curative attempts with multimodal treatment including surgery, chemotherapy (CT) and radiotherapy (RT). VEGF, EpCAM, MUC1, CK19 and CK20 and CD133 have shown to provide additional prognostic information in advanced GEA patients. Methods: Circulating mRNA of total VEGF (and 2 VEGF isoforms 121 and 165), EpCAM, MUC1 and CD133 were determined in 36 loco-regional GEA patients (pts). Blood samples were collected before surgery or, when indicated, before the preoperative chemotherapy treatment, within a 7 days window. Additionally, 14 healthy volunteers and 7 advanced GEA pts were included to comparative analyses. The Wilcoxon test was used to assess differences in expression among the groups. Results: Pre-surgery CT was administered in 30 pts (79%). ECF or its modifications were administered in 22 pts, and FOLFOX in 7 pts. Type of resection achieved was R0 (19 pts, 59%), R1(7 pts, 22%) and R2 (6 pts, 10%). Post-surgery CT was administered in 22 pts (73%) including ECF or its modifications (10 pts), FOLFOX (7 pts) and CT-RT (4 pts). PFS occurred in 19 pts (61%) and 34 patients remained alive at the time of this analysis. Patients diagnosed with loco-regional GEA exhibited over expression as compared to healthy volunteers of VEGFi121 in 17 pts (47%) by 33-fold median change (IQR 5-43, %, p = 0.0008); VEGFi165 in 17 pts (47%) by 15-fold (IQR 5-36, p = 0.002); total VEGF in 19 pts (53%) by 15 fold (IQR 8-59, p = 0.01); EpCAM in 8 pts (22%) by 3-fold (IQR 0.5-3, NS); MUC1 in 19 pts (53%) by 23-fold (IQR7-59, p = 0.0008); and CD133 in 2 pts (6%) by 55-fold (IQR 28-83, NS). CK20 expression was not detected in healthy controls but was detected in 3 patients. Conclusions: VEGF and its isoforms VEGF121 and VEGF165 and MUC1 are potential diagnostic biomarkers in GEA. Due to the short follow-up of patients we cannot yet evaluate their role as prognostic biomarkers.

e15061 Background: The clinical usefulness of tumor markers (TM) as predictors of treatment outcome in advanced EGA has been poorly defined. The aim of this study was to evaluate the prognostic sig...

7509 Background: PM01183 inhibits transactivated transcription and acts on the tumor microenvironment. It lacks cross-resistance with platinum. PM01183 and DOX are synergistic in vitro. Recommended...

201 Background: Advanced gastric cancer (AGC) is a highly lethal disease worldwide with a median overall survival (OS) of less than 12 months. Ramucirumab was the first targeted agent to show survival benefit in the second-line (2L) treatment of AGD. From the REGARD trial, women exhibited a trend towards a worse survival when compared to men. Methods: We retrospectively analyzed the outcome of a Spanish cohort of 55 AGC patients who had received at least two consecutive chemotherapy lines of treatment at our institution. We preselected some clinical parameters (age, gender, Lauren subtype, Her-2 status, grade of differentiation, primary tumor localization and resection, TNM stage, neoadjuvant/adjuvant administration, mono/polychemotherapy in 2L, irinotecan- or taxane-based 2L, Trastuzumab treatment, and administration of third-lines [3L]) to be tested as potential prognostic factors. We focused our analysis on the gender effect in OS after 2L treatment in AGC. The SPSS software package was used for all statistical analyses (Mann-Whitney U test, Chi Square, Kaplan-Meier, Cox regression). Results: Women, diffuse subtype, poorly differentiated tumors, sub-cardia location, single-agent 2L and 3L administration were the clinical characteristics with a significant shorter OS by the univariable analysis. Median OS of women (5 months, 95%CI 3.9-6.0) was significant lower than that in men (13 months, 95%CI 7.9-18.0) by both Log-Rank and Breslow tests (p 0.002). We found no significant differences in age, progression-free survival or time-on-treatment between men and women. Female gender was significantly associated with more taxane-based 2L and with less 3L treatment administration. When 3L treatment administration was excluded in the multivariable analysis, female gender was the only independent prognostic factor of all the clinical parameters included in our review (HR 0.33, 95%CI 0.15-0.75, p 0.008). Conclusions: Our retrospective study found that gender, Lauren subtype, grade of differentiation, primary tumor location, polychemotherapy and 3L administration may be potential prognostic factors in AGC after 2L treatment. Female gender was an independent prognostic factor in our Spanish cohort.