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Background: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. Patients and methods: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). Results: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8- 32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade >= 3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. Conclusions: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade >= 3 TRAEs were more common in patients on combination.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations, Background There is a lack of useful diagnostic tools to identify EGFR mutated NSCLC patients with long-term survival. This study develops a prognostic model using real world data to assist clinicians to predict survival beyond 24 months. Methods EGFR mutated stage IIIB and IV NSCLC patients diagnosed between January 2009 and December 2017 included in the Spanish Lung Cancer Group (SLCG) thoracic tumor registry. Long-term survival was defined as being alive 24 months after diagnosis. A multivariable prognostic model was carried out using binary logistic regression and internal validation through bootstrapping. A nomogram was developed to facilitate the interpretation and applicability of the model. Results 505 of the 961 EGFR mutated patients identified in the registry were included, with a median survival of 27.73 months. Factors associated with overall survival longer than 24 months were: being a woman (OR 1.78); absence of the exon 20 insertion mutation (OR 2.77); functional status (ECOG 0–1) (OR 4.92); absence of central nervous system metastases (OR 2.22), absence of liver metastases (OR 1.90) or adrenal involvement (OR 2.35) and low number of metastatic sites (OR 1.22). The model had a good internal validation with a calibration slope equal to 0.781 and discrimination (optimism corrected C-index 0.680). Conclusions Survival greater than 24 months can be predicted from six pre-treatment clinicopathological variables. The model has a good discrimination ability. We hypothesized that this model could help the selection of the best treatment sequence in EGFR mutation NSCLC patients.

Introduction Patients with cancer may be at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The GRAVID study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19. Methods Prospective observational study that included medical records of patients with lung cancer and PCR-confirmed COVID-19 diagnosis across 65 Spanish hospitals. The primary endpoint was all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU). Results A total of 447 patients with a mean age of 67.1 ± 9.8 years were analysed. The majority were men (74.3 %) and current/former smokers (85.7 %). NSCLC was the most frequent type of cancer (84.5 %), mainly as adenocarcinoma (51.0 %), and stage III metastatic or unresectable disease (79.2 %). Nearly 60 % of patients were receiving anticancer treatment, mostly first-line chemotherapy. Overall, 350 (78.3 %) patients were hospitalized for a mean of 13.4 ± 11.4 days, 9 (2.0 %) were admitted to ICU and 146 (32.7 %) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates. Conclusions Mortality rate was higher among patients treated with corticosteroids during hospitalization, while anticancer therapy was not associated with an increased risk of hospitalization or death. Tailored approaches are warranted to ensure effective cancer management while minimizing the risk of exposure to SARS-CoV-2.

Background Malignant mesothelioma is a rare but aggressive tumor arising from the pleura, typically associated with exposure to asbestos. The purpose of this investigation was to describe mesothelioma patient characteristics, treatment patterns, and outcomes in Spain. Material and methods Patients diagnosed with malignant mesothelioma of the pleura were recorded in an anonymous online database (BEMME, Epidemiologic Spanish Malignant Mesothelioma Database) from June 2008 through May 2013. Patient and tumor characteristics at time of diagnosis, as well as subsequent treatments (surgery, radiation, and chemotherapy), were collected. Among patients treated with chemotherapy, we explored type of chemotherapy regimen and outcomes by treatments. Results A total of 560 malignant pleural mesothelioma (MPM) patients were recorded. The median age at diagnosis was 68 years, mainly with epithelioid histology (62 %), and any asbestos exposure was noted in 45 % of patients. Nearly two-thirds of patients (71 %) received chemotherapy, mainly platinum-pemetrexed combination, as part of their treatment. Surgery and radiotherapy were given in 36 % and 17 % of patients, respectively. The median overall survival (OS) in the whole cohort was 13.0 months (95 % confidence interval (CI), 11.1–14.8 months) with 1-year OS of 53.2 % (95 % CI, 48.7–57.7 %). In patients receiving first-line chemotherapy (N = 315), the median OS was 13.4 months (95 % CI, 10.8–16.0 months), reaching 20.2 months (95 % CI, 17.2–23.2 months) for those 68 patients receiving maintenance chemotherapy. Results of multivariate analyses showed significant association of ECOG-performance status, histology and treatment response with improved OS in MPM patients treated with palliative chemotherapy. Conclusions Despite multimodal therapeutic intervention, survival of patients with mesothelioma in Spain remains poor. Although it did not reach significance in the multivariate analysis, a meaningful additional survival benefit was observed among those patients receiving maintenance chemotherapy.

e18709 Background: Patients with cancer may be more susceptible to infection and at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The LunG canceR pAtients coVid19 Disease (GRAVID) study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19. Methods: In this large nationwide study, we reviewed medical records of patients with lung cancer and confirmed COVID-19 diagnosis from 65 Spanish hospitals. Clinical features, treatments and disease outcomes were collected. The primary endpoint was to determine all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU). Risk factors for poor prognosis were identified by univariate and multivariate logistic regression models. Results: Overall, 447 patients were included for analysis. Mean age was 67·1 ± 9·8 years; 332 (74·3%) were men, and 383 (85·7%) current/former smokers. NSCLC was the most frequent type of cancer (377, 84·5%), consisting mainly of adenocarcinoma (228, 51·0%), and stage III metastatic or unresectable disease (354, 79·2%). Two-hundred and sixty-six (59·5%) patients were receiving anticancer treatment, mostly first-line chemotherapy. In total, 350 (78·3%) patients were hospitalized for a mean of 13·4 ± 11·4 days, nine (2·0%) patients were admitted to the ICU, and 146 (32·7%) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates. Conclusions: Due to their underlying comorbidities and immunocompromised status, patients with lung cancer and COVID-19 show high hospitalization and mortality rates. These outcomes, alongside the identification of prognostic factors, may inform physicians on the risks and benefits in this population, in order to provide individualized oncological care.

BACKGROUND: Biological differences between the sexes have a major impact on disease and treatment outcome. In this paper, we evaluate the prognostic value of sex in stage IV non-small-cell lung cancer (NSCLC) in the context of routine clinical data, and compare this information with other external datasets. METHODS: Clinical data from stage IV NSCLC patients from Hospital Puerta de Hierro (HPH) were retrieved from electronic health records using big data analytics (N = 397). In addition, data from the Spanish Lung Cancer Group (GECP) Tumor Registry (N = 1382) and from a published study available from the cBioPortal (MSK) (N = 601) were analyzed. Survival curves were estimated using the Kaplan-Meier method. A Cox proportional hazards regression model was used to assess the prognostic value of sex. A meta-analysis to compare the outcome for males and females in terms of overall survival (OS) and progression free survival (PFS) was performed. RESULTS: The median OS time was 12 months for males and 19 months for females (overall HR = 0.77; 95% CI: 0.68-0.87; P < 0.001). Similarly, females with stage IV NSCLC harboring an EGFR-sensitizing mutation lived significantly longer than males (median OS: males, 19 months; females, 32 months) with a lower risk of death compared with males (overall HR = 0.75; 95% CI: 0.67-0.84). In addition, female patients benefited more from EGFR inhibitors in terms of PFS and OS (overall HR = 0.45; 95% CI: 0.32-0.64, and HR = 0.62; 95% CI: 0.48-0.80, respectively). Median PFS was 21 months in females and 12 months in males (P < 0.001). CONCLUSIONS: Using routine clinical data we confirmed the previous finding that among stage IV NSCLC patients, females had a significantly better prognosis than males. The effect size of the sex was notable, highlighting the fact that survival rates are usually estimated and patients are generally managed without considering the sexes separately, which may lead to suboptimal results.

Background Target therapy guide by biomarkers have become the standard of care for patients with lung cancer (LC). So, identify those molecular alterations is one of the most important care needs nowdays. Our objective was to know the implementation degree of these tests in a large cohort of patients in Spain using the Thoracic Tumor Registry (TTR) of the Grupo Espanol de Cancer de Pulmon (Spanish Lung Cancer Group). Methods The TTR is an observational cohort multicenter study of LC in Spain. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating institute. The registry was approved by the Spanish Drug Agency as a non-post-authorization, non-interventional study. We analyzed the molecular biomarkers considering all stages of LC. Results A total of 7,872 patients from 58 Spanish centers were enrolled between August 2016 to December 2018. The most frequent screened molecular test was the EGFR mutations, it was performed in 4,456 patients (67.5%). The proportion of biomarker evaluation has varied over time, ranging from 57.9% prior to 2012 up to 73.7% in 2017. The molecular assessment of some biomarkers reached 81.4% of these patients, with some differences between Regional Communities, regarding the molecular tests performed. Three thousand four hundred forty-six (3,446) patients (52.2%) had a stage IV at diagnosis. There was performed some biomarker test in 92% of the 2570 patients with stage IV and non-squamous histology. In those stage IV non-squamous patients, the EGFR and ALK test were performed in 92% and 79% respectively but 2 years ago ALK test was done only in 40% of the patients. ROS1 was studied in 20% of the cases. Conclusions Although no national plan exists for molecular biomarker analysis in Spain, the implementation of biomarkers tests in all the hospitals that contribute to the TTR is high. The increase in the ALK analysis in the last period is relevant. As we have some regional differences, it is important to understand the causes to improve them. Clinical trial identification NCT02941458. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Novartis, Merck Sharp and Dohme, Lilly. Disclosure All authors have declared no conflicts of interest.

Background Tobacco use, mainly as cigarette smoking, is the leading cause of lung cancer. Eighty-five percent of LC occur in smokers. Understanding the Spanish smoking habits allows the government to design health care policies against this consumption. To do so, the Grupo Espanol de Cancer de Pulmon (Spanish Lung Cancer Group) made this analysis within the context of the Thoracic Tumor Registry (TTR). Methods The TTR is an observational cohort multicenter study in Spain. The study is conducted according to the Declaration of Helsinki and approved by the institutional review board of each participating site. The registry was approved by the Spanish Drug Agency, as a non-post-authorization, non-interventional study. Results Data have been collected from 6,600 LC from 58 different hospital sites across Spain. 12% (866 p) were non-smokers, 46% (3,039 p) were former smokers and 39% (2,611 p) were smokers. There were significant differences by gender, more women were non-smokers (37 % vs. 45% in males), meanwhile more former smokers were male (53.4% vs. 27.9% in women) (p-valor Conclusions Tobacco use is the leading cause of LC in Spain accounting 85% of the cases. Consumption has increased in both genders, but specially in women, in our country among lung cancer patients. Tobacco cessation campaigns, especially in women, should be a priority in western countries, like Spain, and it has to be adapted to regional differences in tobacco use. 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 CT-RT is the standard treatment for unresectable LA-NSCLC. P plus vinorelbine is widely used. Metronomic CT is a frequent administration of low doses of CT. mOV has shown good efficacy and improved safety, and could improve the RT effect. Our goal is to evaluate the efficacy and safety of P-mOV with radical RT in patients (pts) with LA-NSCLC. Methods Pts aged 18-75 years with histologically proven untreated and unresectable LA-NSCLC, adequate bone marrow, hepatic & renal function, ECOG PS0-1, received P 80mg/m2 D1 every 3 weeks combined with mOV 50mg/day on days D1, 3 & 5/weekly, 2 cycles (cy) as induction; patients without progression received 2 more cy of P at the same dose with mOV 30mg/day on D1, 3 & 5/weekly, concurrently with RT (66Gy in 6.5weeks). Primary endpoint was progression-free survival (PFS) by RECIST v1.1; secondary endpoints were: overall response rate (ORR), disease control rate (DCR), overall survival and safety profile. To guarantee an overall type-1 α error no greater than 0.05 and a type II (β) error 0.1 for PFS, a sample size of 67 pts was planned. Results Sixty-seven pts were recruited in 17 Spanish sites from 04/2016 to 06/2017. One of them didn’t meet all the inclusion criteria. We analyzed 66 pts included. Pt characteristics: Male 77.3%; median age 62 (range 33-75); PS 0/1 52/49%; smokers 53%; adenocarcinoma/squamous 43.9/42.4%; stage IIIA/B 42.4/57.6%. Only 32.3% of pts presented any grade 3-4 adverse event, including: neutropenia 20.0%; anemia 4.6%; febrile neutropenia 6.2%; esophagitis 3.1%; pneumonitis 1.5%. There were two deaths non-related to the treatment, during this period. Fifty-one pts have completed the treatment. ORR: 67.7%. DCR: 84.6%. With a median follow-up of 22.3 months (range 1.1-34.9), the median PFS is 11.5 months (CI95%; 9.9-15,4). Conclusions mOV-P with RT is as effective as the standard administration of vinorelbine, improving its safety profile. Clinical trial identification EudraCT 2015-003312-21. Legal entity responsible for the study Spanish Lung Cancer Group. Funding Pierre Fabre. Disclosure All authors have declared no conflicts of interest.