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PURPOSE Venous thromboembolism (VTE) is a leading cause of death among patients with cancer. The Khorana score was developed for assessing the risk of VTE in outpatients with cancer receiving chemotherapy, but its accuracy in identifying patients at high risk has been questioned. The aim of this study was to develop and validate a clinical-genetic score that improves the assessment of VTE risk in oncology outpatients within 6 months of diagnosis. METHODS The new score was developed using the data of 364 outpatients belonging to the Spanish ONCOTHROMB 12-01 population. In this cohort, clinical data associated with the risk of VTE were collected at the time of diagnosis, including the Khorana score. These patients were also genotyped for the 51 genetic variants known to be associated with VTE. Multivariate logistic regression was performed to determine the weight of each genetic and clinical variable in relation to VTE risk, allowing a clinical-genetic risk score (the ONCOTHROMB score) to be developed. The Khorana and the ONCOTHROMB scores were then compared via the area under the receiver operating characteristic curve (AUC), calibration, and the number of patients needed to treat. The new score was then validated in a study of 263 patients in the Vienna Cancer and Thrombosis Study population. RESULTS Nine genetic variants, tumor site, TNM stage, and a body mass index of > 25 kg/m2 were found to be associated with VTE and were used to build the ONCOTHROMB score, which better predicted the overall risk of VTE than did the Khorana score (AUC, 0.781 v 0.580; P < .001). Similar AUC results were recorded in the validation study the Vienna Cancer and Thrombosis Study cohort involving patients with the same type of tumor (AUC for the ONCOTHROMB score v the Khorana score: 0.686 v 0.577; P < .001) and with all type of tumors (AUC for the ONCOTHROMB score v the Khorana score: 0.720 v 0.561; P < .0001). CONCLUSION The ONCOTHROMB score for VTE risk in outpatients with cancer, which takes into account both clinical and genetic variables, better identifies patients who might benefit from primary thromboprophylaxis than does the Khorana score.

Background: Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe as maintenance therapy for recurrent platinum-sensitive (Pt-S) ovarian cancer (OC). The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for the above-mentioned indication, as well as for patients with BRCA-mutated Pt-S or platinum-resistant (Pt-R) OC and no therapeutic alternatives. Methods: In this observational, retrospective study we analysed the efficacy and safety of rucaparib within the RAP in Spain. Hospitals associated with the Spanish Ovarian Cancer Research Group (GEICO) recruited patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer treated with rucaparib 600 mg twice daily as maintenance or treatment (Pt-S/Pt-R) in the RAP. Baseline characteristics, efficacy, and safety data were collected. Results: Between July 2020 and February 2021, 51 patients treated in 22 hospitals in the RAP were included in the study. Eighteen patients with a median of 3 (range, 1–6) prior treatment lines received rucaparib as maintenance; median progression-free survival (PFS) for this group was 9.1 months (95% confidence interval [CI], 4.2–11.6 months). Among 33 patients (median 5 [range, 1–9] prior treatment lines) who received rucaparib as treatment, 7 and 26 patients had Pt-S and Pt-R disease, respectively. Median PFS was 10.6 months (95% CI, 2.5 months-not reached) in the Pt-S group and 2.2 months (95% CI, 1.1–3.2 months) in the Pt-R group. Grade ≥ 3 treatment-emergent adverse events were reported in 39% of all patients, the most common being anaemia (12% and 15% in the maintenance and treatment groups, respectively). At data cut-off, 5 patients remained on treatment. Conclusion Efficacy results in these heavily pre-treated patients were similar to those from previous trials. The safety profile of rucaparib in real life was predictable and manageable.

e17598 Background: Rucaparib is a PARP inhibitor (PARPi) approved as maintenance therapy for platinum (Pt)-sensitive recurrent high-grade ovarian cancer (HGOC), and as treatment for BRCA-mutant HGOC patients. To date, there is little evidence about the efficacy and safety of rucaparib after prior exposure to PARPi. This subanalysis aims to describe the patients’ characteristics and treatment outcomes with rucaparib in women who were included in the rucaparib early access program (RAP) in Spain and had received a prior PARPi. Methods: A retrospective study was conducted by GEICO at 22 hospitals in Spain to analyze data of 51 women treated within the RAP (600 mg BID). Adult women with HGOC, fallopian tube, or primary peritoneal cancer, who had received at least one prior PARPi before rucaparib were analyzed. Patients’ characteristics, medical history, safety, efficacy, and dosing data were collected. Results: A total of 14 women, with a median age of 63 years old (42-78) were included in this subanalysis. Of them, 92.9% were diagnosed of epithelial ovarian cancer and 78.6% had mutations in BRCA1/ 2 genes. The median number of lines before rucaparib was 5 (3-8), while the number of lines before the first PARPi was 3 (2-5). Except for one woman who had received 2 prior PARPis before rucaparib, the others had received just 1. Most patients were given olaparib as the first PARPi (n = 12, 85.8%), while niraparib was the initial PARPi in the remaining cases (n = 2, 14.3%). The outcomes of the treatment with rucaparib in these patients are outlined in table 1. Rucaparib was given as maintenance therapy in 1 patient and as treatment in 13 patients, 12 of them being Pt-resistant. The progression-free survival (PFS) ranged from 0.23 to 9.12 months. Adverse events (AE) of any grade were detected in 78.6% of patients, whereas AE of grade ≥3 affected 28.6% of women. Rucaparib dose was interrupted in 57.1% and reduced in 42.9% of patients. Only 1 patient discontinued rucaparib due to toxicity. No new safety signals were detected. Conclusions: This is one of the first real-word studies reporting the use of rucaparib after treatment with another PARPi. Even in these heavily pre-treated patients who had received prior PARPi, rucaparib efficacy has been notable in some cases, and its safety profile is consistent with that reported in previous clinical trials. Future studies should focus on the selection of patients who could benefit from rucaparib after prior PARPi exposure. [Table: see text]

e17562 Background: Rucaparib is a PARP inhibitor approved for the treatment of high-grade ovarian cancer (HGOC). Clinical trials have demonstrated its benefit both as maintenance therapy (MTN) for platinum (Pt)-sensitive recurrent HGOC, and as treatment (Tx) in BRCA-mutated relapsed or recurrent HGOC patients. Here we analyze real-world data from the rucaparib early access program (RAP) in Spain with focus in the long-term responder patients (LTR). Methods: A retrospective observational study was performed by GEICO at 22 hospitals in Spain that had treated patients within the RAP. Adult women with HGOC, fallopian tube, or primary peritoneal cancer were included and received rucaparib (600 mg BID) in the MTN, Tx Pt-sensitive or Tx Pt-resistant setting. Patients’ characteristics, medical history, safety, efficacy, and dosing data were collected. In this analysis, long-term response was defined as progression-free survival (PFS) ≥12 months for the MTN group and ≥6 months for the Tx group. LTR were stratified based on the rucaparib indication (MTN/Tx). Results: Between July 2020 and February 2021, 51 patients were recruited: 18 received rucaparib as MTN and 33 as Tx. In the MTN group, 6 patients (33.3%) were LTR, with a median age of 65 years (54-79). Of them, 2 patients (33.2%) harbored BRCA or RAD51C mutations. The median number of prior lines was 3 (2-6), being ≥5 in 33.2%, and 50.0% received prior bevacizumab. ECOG PS was ≤1 in all these patients, 66.6% had measurable disease and 50.0% achieved a partial response to prior Pt-based chemotherapy. In the Tx group, 10 patients (30.3%) were LTR, with a median age of 71 years (47-86). All of them harbored BRCA and/or RAD51C mutations. The median number of prior lines was 6 (2-9), with 60.0% receiving ≥5 prior lines, and 50.0% received prior bevacizumab. Regarding Pt-status, 40.0% of patients were Pt-sensitive and 60.0% were Pt-resistant. The ECOG PS was ≥1 in 30.0% of patients and 60.0% had measurable disease. The median PFS of LTR was not achieved in the MTN group and was 10.9 months (95% CI: 7.0-16.7) in the Tx group. Adverse events (AE) of any grade were reported in 66.6% of LTR within the MTN group and in 100.0% within the Tx group, while AE of grade ≥3 occurred in 16.6% and 50.0%, respectively. Rucaparib dose was reduced in 50.0% of LTR in the MTN group and 80.0% in the Tx group. Discontinuation rate due to rucaparib toxicity was 20.0% in the Tx group and there were no discontinuations due to toxicity in the MTN group. No new safety signals were detected. At present, 3 and 1 patients are still receiving rucaparib as MTN and Tx, respectively. Conclusions: A durable response was achieved in a notable proportion of patients, even despite their unfavorable conditions at treatment initiation (heavily pre-treated patients, partial response or resistance to Pt, or high volume of disease). The safety profile of rucaparib in this real-world setting is consistent with that reported in clinical trials.

Background Small-cell lung cancer (SCLC) is an aggressive disease with high metastatic potential and poor prognosis. Due to its low prevalence, epidemiological and clinical information of SCLC patients retrieved from lung cancer registries is scarce. Patients and methods This was an observational multicenter study that enrolled patients with lung cancer and thoracic tumors, recruited from August 2016 to January 2020 at 50 Spanish hospitals. Demographic and clinical data, treatment patterns and survival of SCLC patients included in the Thoracic Tumor Registry (TTR) were analyzed. Results With a total of 956 cases, the age of 64.7 ± 9.1 years, 78.6% were men, 60.6% smokers, and ECOG PS 0, 1 or ≥ 2 in 23.1%, 53.0% and 23.8% of cases, respectively. Twenty percent of patients had brain metastases at the diagnosis. First-line chemotherapy (CT), mainly carboplatin or cisplatin plus etoposide was administered to >90% of patients. In total, 36.0% and 13.8% of patients received a second and third line of CT, respectively. Median overall survival was 9.5 months (95% CI 8.8–10.2 months), with an estimated rate of 70.3% (95% CI 67.2–73.4%), 38.9% (95% CI 35.4–42.4%), and 14.8% (95% CI 11.8–17.8%) at 6, 12 and 24 months respectively. Median progression-free survival was 6.3 months. Higher mortality and progression rates were significantly associated with male sex, older age, smoking habit, and ECOG PS 1–2. Long-term survival (> 2 years) was confirmed in 6.6% of patients, showing a positive correlation with better ECOG PS, poor smoking and absence of certain metastases at diagnosis. Conclusion This study provides an updated overview of the clinical situation and treatment landscape of ES-SCLC in Spain. Our results might assist oncologists to improve current clinical practice towards a better prognosis for these patients.

Background and Aim: In Stage IIIA-N2 non-small cell lung cancer (NSCLC), the accuracy of combined positron-emission tomography/computed tomography imaging (PET-CT), together with mediastinal staging techniques, has led to a wide range of challenging clinical scenarios in terms of therapeutic management. Concurrent chemoradiotherapy followed by consolidation immunotherapy remains the standard of care. In patients with potentially-resectable disease, surgery plays an important role in multimodal therapy. The introduction of targeted therapies and immune-checkpoint inhibitors has revolutionized multimodal treatment. In the present article, we review current treatment options and future trends in stage IIIA-N2 NSCLC. Relevance for Patients: This article provides insight into the current status of multimodal treatment for NSCLC to support decision-making in routine clinical practice.

Objective: We assessed trabectedin in patients with advanced uterine leiomyosarcoma (uLMS) in real-life clinical practice given according to the marketing authorization. Methods: Thirty-six women from 11 tertiary hospitals across Spain who received trabectedin after anthracycline-containing regimen/s were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Results: Median PFS and overall survival (OS) since starting trabectedin treatment were 5.4 (95%CI: 3.5-7.3) and 18.5 months (95%CI: 11.5-25.6), respectively. Median OS was significantly higher (P = 0.028) in patients receiving trabectedin in = 3rd (15.1 months) and with ECOG performance status = 2nd line/s (0.0% and 20.0%), whereas the DCR was similar across treatment lines. Reversible neutropenia was the most common grade 3/4 laboratory abnormality (19.4%). Conclusions: Trabectedin confers clinical benefit in patients with recurrent/metastatic uLMS, given after failure to an anthracycline-based regimen being comparable to those reported in clinical trials and with a manageable safety profile., This study was supported by funding from PharmaMar (Madrid, Spain).

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death among patients with cancer. Outpatients with cancer should be periodically assessed for VTE risk, for which the Khorana score is commonly recommended. However, it has been questioned whether this tool is sufficiently accurate at identifying patients who should receive thromboprophylaxis. The present work proposes a new index, TiC-Onco risk score to be calculated at the time of diagnosis of cancer, that examines patients' clinical and genetic risk factors for thrombosis. METHODS: We included 391 outpatients with a recent diagnosis of cancer and candidates for systemic outpatient chemotherapy. All were treated according to standard guidelines. The study population was monitored for 6 months, and VTEs were recorded. The Khorana and the TiC-Onco scores were calculated for each patient and their VTE predictive accuracy VTEs was compared. RESULTS: We recorded 71 VTEs. The TiC-Onco risk score was significantly better at predicting VTE than the Khorana score (AUC 0.73 vs. 0.58, sensitivity 49 vs. 22%, specificity 81 vs. 82%, PPV 37 vs. 22%, and NPV 88 vs. 82%). CONCLUSIONS: TiC-Onco risk score performed significantly better than Khorana score at identifying cancer patients at high risk of VTE who would benefit from personalised thromboprophylaxis.

Background Lung cancer is the leading cause of cancer mortality worldwide with more than 2 million new cases and 1.8 million deaths in 2018. The TTR could be of use to objectively understand the clinical reality of lung cancer in Spain. Methods Observational cohort multicenter study performed in Spain. Enrollment took place between Aug’16 and Dec’18. Evaluation included a review of demographic data. Results 6600 patients in 56 Spanish hospitals were included. Median age at diagnosis was 64 in advanced disease and 65 in early-stage. The majority of patients presented with advanced, stage III (n = 1874, 28.4%) or IV (n = 3446, 52.2%) at diagnosis, independently of gender (63.1% in males; 70.6% in females). There was a higher number of patients with no comorbidities at diagnosis in advanced disease than in early-stage (63.4% vs. 36.6%, p Conclusions The RTT provides information on comorbidities, risk associations, personal and family history of cancer necessary for the knowledge of lung cancer in real life, which could even be useful when planning the analysis of national health policies. Clinical trial identification NCT02941458. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Novartis, MSD, Lilly. Disclosure M. Provencio: Advisory / Consultancy: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Background Peritoneal dissemination is the most common route of spread of epithelial ovarian cancer (EOC). Cytoreductive surgery (CRS) followed by platinum-based systemic chemotherapy is the current standard treatment in advanced stages, with suboptimal results. The aim of this study is to analyze the outcome of advanced EOC treated with CRS plus hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) combined with systemic chemotherapy. Methods We analyze a cohort of women treated with CRS plus HIPEC for peritoneal carcinomatosis secondary to EOC from May 2007 to December 2014. We included both patients with peritoneal disease at first diagnosis of EOC and peritoneal recurrences after initial treatment. Results We performed 61 CRS with HIPEC procedures, 31 cases as primary treatment (4 as upfront therapy and 27 after neoadjuvant chemotherapy) and 30 as secondary treatment (recurrences). Median Peritoneal Carcinomatosis Index (PCI) was 9; the cytoreduction was optimal in 92% of the procedures. Severe morbidity (Grade III-IV of Clavien-Dindo classification) was 29.5%, without mortality. Median follow-up was 23 months and median disease-free survival (DFS) was 14 months (14 in primary surgery group and 17 in recurrence group, P=0.51). Median overall survival (OS) was 57 months; in primary surgery group, OS was 96.8% at 1 year, and 55% at 5 years, and median OS was not reached; OS in recurrence group was 89.3% at 1 year and 47.1% at 5 years, and median OS was 57 months. Conclusions CRS with HIPEC is a treatment option for EOC with good results in terms of morbidity and survival, in experienced centers.

e13608Background: The Spanish Lung Cancer Group (GECP) initiated a Tumor Thoracic Register (RTT) in September 2016 with the aim of evaluating accurate, basic data concerning this oncological pathol...

La afectacion cardiaca por enfermedades neoplasicas puede deberse a invasion cardiaca por el propio tumor, a compresion del corazon y/o de los grandes vasos por neoplasias extracardiacas, embolizacion y fundamentalmente a los efectos de la terapeutica antitumoral. El tratamiento del cancer ha experimentado un importante avance en las ultimas decadas por la gran expansion de agentes quimioterapicos y el refinamiento de las tecnicas de radioterapia; no obstante, muchos de los mas efectivos farmacos antineoplasicos y la irradiacion toracica ocasionan cardiotoxicidad aguda y cronica. Asi, el seguimiento a largo plazo de pacientes que han recibido antraciclinas, farmacos cruciales en la terapia de muchas neoplasias, demuestra fallo cardiaco clinico en el 4,5 al 7% de los pacientes, incrementandose la incidencia de anomalias en la funcion cardiaca con el tiempo. Su patogenia probablemente incluya la formacion de radicales libres, alteraciones en el transporte del calcio, disfuncion adrenergica o liberacion de aminas vasoactivas. El dexrazoxano es el unico cardioprotector de uso clinico comercializado para un grupo seleccionado de pacientes con carcinoma de mama, por lo que es necesario el desarrollo de nuevos agentes que protejan de la cardiotoxicidad de este grupo de farmacos y reduzcan la morbimortalidad secundaria a los mismos.

PURPOSE To evaluate the impact of the selection criteria that are used in current high-dose consolidation chemotherapy (HDCT) trials on the outcome of high-risk breast cancer patients treated with conventional adjuvant chemotherapy. PATIENTS AND METHODS From 1975 to 1995, 265 breast cancer patients at our institution showed involvement of ten or more positive axillary lymph nodes. Of these, 171 received standard adjuvant combination chemotherapy, but not HDCT consolidation, and were the subjects of our study. One hundred twenty-eight patients met the standard selection criteria for HDCT with hematological support (< 60 years, no significant concomitant disease, and no progression during adjuvant treatment), whereas 43 did not. Clinical outcome was analyzed by using disease-free survival (DFS) and overall survival (OS) as endpoints. To provide an assessment of the short-term efficacy of HDCT, we also evaluated the outcome in a cohort of 39 patients from the last 4 years who met the criteria for, and were actually treated with, HDCT after adjuvant chemotherapy. RESULTS With a median follow-up of 4.4 years (range, 0.7 to 17.2 years), 112 of the 171 patients have had a relapse, and 87 have died. The estimated 5-year DFS was 32.3%, and OS was 49.4%. DFS was significantly higher for patients who met the HDCT criteria (36.6% at 5 years) than for those who did not (15.8% at 5 years; P < .05). OS was also significantly more favorable in patients meeting HDCT criteria (55.4% at 5 years) than in patients not meeting HDCT criteria (22.7% at 5 years; P < .01). We performed a multivariate analysis to adjust for other potential prognostic factors and found that meeting the HDCT criteria and having undergone locoregional radiotherapy were the only significant independent predictors for DFS and OS. Finally, we compared the outcome of the 128 patients who met the HDCT criteria and were treated with conventional adjuvant chemotherapy only with that of the 39 patients who met the criteria and who actually underwent HDCT, and we did not observe significant differences in the DFS or OS between these groups. CONCLUSIONS Meeting HDCT inclusion criteria is an independent indicator of favorable prognosis in high-risk breast cancer patients. The selection of patients by these criteria may explain, at least in part, the promising short-term results of nonrandomized adjuvant HDCT trials in high-risk breast cancer.

e22112 Background: Detection of EGFR m in p with NSCLC is done in a routine way. Given the data published on ALK positive p detection is crucial for therapeutic decision making. ALK t should be per...

Summary Background: The aim of this study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine plus cisplatin, administered every three weeks, in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods: Twenty-six previously untreated stages III (14) and IV (12) patients were included. Gemcitabine was administered on days 1 and 8 at a dose of 1250 mg/m 2 and cisplatin was administered at a dose of 100 mg/m 2 on day 1, every 21 days. Results: Twenty-five patients were evaluable for response. One patient achieved a complete response, and 16 patients partial responses. The overall response rate was 65.3% (95% CI: 45%-82%). The main toxicity was hematological: neutropenia NCIC-CTC grade 3-4 in 54% of the patients, and thrombocytopenia grade 3-4 in 23%. The non-hematological toxicity was mild and tolerable. Only 13% of gemcitabine injections were dose-reduced or omitted due to toxicity. The actual dose-intensity of gemcitabine was 715 mg/m~/week, and 31 mg/nr/week for cisplatin. These figures represent the 86% and 93% of the theoretical dose intensity of both drugs, respectively. With a median follow-up of 10 months (range 7-13), 17 patients are still alive and nine have died. The median overall survival is 12 months. Conclusion: This novel combination of gemcitabine and cisplatin administered every three weeks is well tolerated and induces a remarkably high response rate. The regimen proves more interesting than the four-week schedules, particularly regarding patients who are candidates for local therapy.