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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.

The outbreak of the new coronavirus disease (COVID-19) has become the greatest threat to public health worldwide. Oncological patients have an increased risk of infection due to their oncological disease, which supresses the immune system and mielosupressive effects of antincancer treatments. Throughout this article, the impact of COVID-19 in the oncological field will be reviewed, centering in diagnosis (susceptibility, differential diagnoses, delays in diagnosis in post-COVID era, triage systems); treatment (treatment of COVID-19 infection, surgeries, oncological treatments); impact in mortality and emotional impact. Maintaining quality of care in patients as vulnerable as cancer patients is a huge challenge in the face of possible outbreaks or future times when we have to face living with the infection but maintaining quality standards in healthcare.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR)= 1.02 (0.66-1.58), two-sided P= 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR= 0.95 (0.59-1.52), P= 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade =3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

Introduction: There are currently no predictive biomarkers for long-term survival after neoadjuvant chemoimmunotherapy. However, the identification of non-small lung cancer (NSCLC) patients who obtain long-term benefit from chemoimmunotherapy is essential to optimize therapies. Methods: Using samples from NADIM clinical trial (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with nivolumab, we have evaluated the capacity of ctDNA levels before treatment initiation to predict overall survival (OS) and progression-free survival (PFS) by calculating Harrell’s C-statistic and we compare its predictive value with classical survival surrogates as the pathological response and clinical response assessed according to RECIST criteria v.1.1. The ctDNA was analyzed by NGS, using the Oncomine Pan-Cancer Cell-Free Assay™ (Thermo Fisher Scientific®). To explore the prognostic value of the amount of ctDNA at baseline, for each positive plasma sample, we calculated the sum of the mutant allele frequency (MAF) for all detected mutations. Patients who died from COVID19 were excluded from this analysis. Results: In our study, clinical responses based on RECIST criteria were not predictive for OS or PFS. On the contrary, in the multivariate analysis, patients with low ctDNA levels (

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, Background We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC). Patients and methods VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and 1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m2 then 250 mg/m2 weekly) plus FOLFIRI [irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 (bolus) then 2400 mg/m2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory. Results Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups. Conclusions BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy, This work was supported by Roche Farma S.A (no grant number). Medical writing support was funded by Roche Farma S.A and provided by H. Lamb and L. Miller of Miller Medical Communications Ltd.

Background and importance Biological treatments represent a great opportunity but their increasing and widespread use is causing sustainability problems in health systems due to their high cost. Emergence of biosimilars can lead to significant savings for health systems. Aim and objectives The aim of this study is to analyse the impact of the introduction of the biosimilar adalimumab (BA) (Hyrimoz) in three different scenarios, to choose the most convenient. Material and methods Firstly, we took into account all patients treated with the reference adalimumab (RA) between 2013 and 2018 to calculate the average incidence for every quarter. Also, we calculated prevalence on 31 December 2018. We then made a quarterly consumption forecast for the next three years (2019–2021). Secondly, we created an excel model for three possible scenarios: (1) all patients treated with RA, (2) the introduction of BA only in new patients with old patients continuing with RA or (3) all patients treated with BA. In every scenario, we calculate costs of buying adalimumab in each year. Finally, to assess the robustness of the data, different deterministic sensitivity analyses were conducted changing ±10% the three variables considered to have more impact in our model (price of adalimumab, incidence and prevalence). Also, an extreme analysis was performed for the best and worst conditions. Results Despite the increasing costs in all scenarios due to a growing incidence, costs would vary from 4 million in 3 years (scenario 1), 3.5 million (scenario 2), to 2.7 million (scenario 3). The choice of the different scenarios would mean savings of 11.5–31.8%, depending on the number of patients who were treated with BA. Sensitivity analyses showed that the cost of adalimumab was the most important factor in the final cost results. Analysis of extreme conditions showed a 20% variation from base case with savings of about 11.5% (scenario 2) and 30% (scenario 3). The most convenient was scenario 3 (change patients already treated with RA and treat new patients with BA). Conclusion and relevance Despite scenario 3 providing the greatest savings (making it possible to treat a large number of patients), the authorities decided not to change patients currently treated with RA, loosing savings of about 20.33%. References and/or acknowledgements Conflict of interest No conflict of interest

8531 Background: Coronavirus disease 2019 (COVID-19) is diagnosed by detecting the virus by reverse transcription polymerase chain reaction (RT-PCR). The majority of p go on to develop antibodies (Ab) against viral proteins. However, it is not known how long these antibodies last nor whether cancer treatments could affect the duration of immune response. The prognosis and greater or lesser vulnerability of the oncological population are also unknown. Methods: This prospective, longitudinal, multicenter serological study in the setting of SARS-CoV-2 was carried out in 50 Spanish hospitals. Eligibility criteria was a diagnosis of any thoracic cancer. The first determinations were performed between April 21, 2020 and June 3, 2020, either for p in follow up or in active treatment. Between September 10, 2020, and November 20, 2020, the second antibody (Ab) determination was performed in all previously seropositive p. Clinical and treatment data were collected, as was their clinical situation at study end. Study objectives were to prospectively determine seroprevalence in unselected lung cancer p during the first wave of the pandemic; the natural history of these p; the persistence of immunity more than 4 months after first determination; protection or lack thereof against reinfection after this period, and the nature of such protection; and the influence of treatments on maintenance or loss of immunity. Results: Of 1,500 p studied, 128 were seropositive, representing an overall prevalence of 8.5% seropositivity [95% confidence interval [CI], 7.2%, 10.1%]. Seventy-five percent were in active cancer treatment. COVID-19 infection was suspected in 47.7% [95% CI, 38.8%, 56.6%]. A second determination was performed on average 4.5 months later [IQR: 4; 5] and obtained for 104 of the initially seropositive p (81%). A second determination could not be obtained in 24 p, the majority due to death caused by disease progression (73%). In the second determination, IgG was not detected in 30.8% (32/104) of p. The severity of the infection, the need for hospitalization (p: 0.032) and the presence of symptoms at diagnosis (p: 0.02), including fever (p: 0.005) and nasal congestion (p: 0.005), were associated with persistence of immunity in the second determination. No variables or treatments received were associated with Ab loss. At time of last follow-up among those p for whom a second determination was performed, 89% (93 p) had completely recovered from the virus, with no lasting after effects. Only 1 of the 128 (0.78%) seropositive p had died from COVID-19. Conclusions: The prevalence of infection in lung cancer p is similar to that of the general population. Immunity against SARS-CoV-2 does not appear to be compromised by treatment, persisting beyond 4 months. Neither do mortality rates appear to be particularly high in this unselected population.

Introduction: Neoadjuvant chemoimmunotherapy been shown to be highly effective in resectable stage IIIA NSCLC. Now we provide long term survival data Methods: This was an open-label, multicentre, single-arm phase 2 trial in which patients with histologically or cytologically documented stage IIIA NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 and who were deemed locally to be surgically resectable by a multidisciplinary clinical team were treated with neoadjuvant intravenous paclitaxel (200 mg/m2) and carboplatin (area under curve 6;6 mg/mL per min) plus nivolumab (360 mg) on day 1 of each 21-day cycle, for three cycles before surgical resection, followed by adjuvant intravenous nivolumab monotherapy for 1 year (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). Here we report progression-free survival (PFS) and Overall survival (OS) at 36 and 42 months, assessed in the modified intention-to-treat population (ITT), which included all patients who received neoadjuvant treatment, and in the per-protocol population (PP), which included all patients who had tumour resection and received at least one cycle of adjuvant treatment. Results: Median follow-up time was 37.9 months (95%CI: 36.7-40.7), with a 94% maturity at 36 months. Among the ITT population (N=46), 37 patients, constituting the PP population, received subsequent adjuvant therapy. Of them, 27 (58.7%) patients completed the adjuvant treatment (16 cycles), 10 (21.7%) patients received between 3 and 15 cycles of adjuvant therapy, and 9 (19.6%) patients did not receive adjuvant therapy. At the time of data cutoff (March 2021), progression disease was diagnosed in 14 patients and 9 deaths were recorded in the ITT population. Of these, three deaths corresponded to patients who did not undergo surgery and had disease progression, four deaths corresponded to patients who underwent surgery and had disease progression, and the two remaining deaths corresponded to patients who were diagnosed as being disease free but died from COVID19 infection. Notably, among patients who could not undergo surgery (N=5), one of them is still alive and with no evidence of disease. PFS at 36 and 42 months in the ITT population were 69.6% (95%CI: 54.1-80.7), in both cases. Similarly, PFS at 36 and 42 in the PP population were 81.1% (95%CI: 64.4-90.5) in both cases. The percentage of patients who were alive at 36 and 42 months in the modified ITT population were 81.86% (95% CI: 66.8-90.6) and 78.94% (95%CI: 63.1-88.6), respectively. Likewise, OS at 36 and 42 months in the PP population was 91.0% (95%CI: 74.2-97.0) and 87.3% (95%CI: 69.3-95.1), respectively. Conclusion: The efficacy of nivolumab in combination with platinum-based chemotherapy in patients with resectable stage IIIA NSCLC is clearly supported by long term survival data. Keywords: NADIM trial, neoadjuvant chemo-therapy, long term survival

Background: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored. Materials and methods: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR. Results: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRASG12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRASG12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRASG12C patients tested negative for the presence of p.T790M resistance mutation. Conclusions: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRASG12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature, This work was supported by CLARIFY project (https://www.clarify2020.eu/). ES-H was supported by the Consejería de Ciencia, Universidades e Innovación of the Comunidad de Madrid (Doctorados Industriales of the Comunidad de Madrid) [grant number IND2019/BMD-17258]. EG-V was supported by AECC (Asociación española Contra el Cáncer) grant ‘Programa de Prácticas de Laboratorio de curso académico AECC 2020’ (no grant number).

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: Madrid has been the epicenter of the SARS-CoV2 pandemic in Spain. We analyzed the experience at our hospital with SARS-CoV2 infection and cancer patients (p). Method(s): We analyzed our experience from March 1 to April 30 at the Puerta de Hierro University Hospital in Madrid. Diagnosis of SARS-CoV2 infection was made by RT-PCR, suspected cases not confirmed were excluded. Result(s): Overall in-hospital mortality cancer p with COVID-19 was 15.2% (95%CI, 6.3;5.2), similar to 12.7% (95%CI,11.1;4.4) with p=0.615 of the global COVID-19 hospitalised population and greater than that of patients admitted without SARS-CoV-2 infection during the same period 4.3% (95%CI;3.6;5.2) p0.001. Among 653 patients receiving active cancer therapy during this period, 24 (3.7%) developed COVID-19 and required admission, 4.2% of were receiving chemotherapy, 9.5% immunotherapy and 2.1% targeted therapies. Lung and breast cancer were the most frequent (26.1%), followed by colorectal (19.6%) and breast cancer. No significant differences due to the cancer treatment received were observed. Mortality in lung cancer patients was the highest (25%). The univariate analysis (between p who developed serious event vs. those who did not), showed that higher Brescia, CURB-65 scale, lactate dehydrogenase (LDH) or C-reactive protein (CRP) levels at admission, the greater risk of developing severe complications (p0.05) [Formula presented]. Conclusion(s): Patients with cancer, especially lung cancer, and SARS-CoV2 infection have a worse overall prognosis than the general population. Objective parameters such as LDH, CRP at admission, Brescia index or CURB-65 should alert us to a more serious evolution and suggest early an early intensive care unit (ICU) admission. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2020

Background Palliative care units (PCU) have shown an improvement in the quality of life of patients with cancer by reducing overtreatments at the end of life and increasing symptomatic care at home, avoiding unnecessary emergency room visits and decreasing the number of hospital admissions. Methods A retrospective observational study was conducted, selecting all patients with a first consultation in the Medical Oncology Unit of the Puerta de Hierro University Hospital (HUPdH) between 2014 and 2015 and died before December 31st 2017. Assessment by PCU, number of hospital admissions and re-admissions and most frequent symptoms for admission in the last 6 months of life were reviewed. The main objective was to know if there were differences between those who were valued by PCU or not. Results A total of 662 patients were selected. From them, 86 (13%) patients had never been admitted at HUPdH, 312 (47%) had been admitted once, 169 (26%) twice and 95 (14%) three or more times. Before death, 474 (72%) had been valued by PCU and 302 did not received PCU visit before the second hospital admission episode. The three most frequent causes of admission were deterioration of the general condition, infections and uncontrollable pain. In those with an assessment by PCU before the second admission process, there was a significant decrease in the number of readmissions (25% versus 68%). Moreover, in these patients, there was a statistically significant decrease in the number of re-admissions because of the three main causes of admission but also in others, such as dyspnea, neurological worsening, bleeding and nauseas and vomiting. (Table). Table . 1606P PCU: Percentage of patients re-admitted with an assessment by palliative care unit by the time of re-admission; Non PCU: Percentage of patients re-admitted without assessment by palliative care units before re-admission Symptom PCU Non PCU Risk Ratio Deterioration of the general condition 9% 21% RR 0.41, 95% CI 0.27-061, p Dyspnea 3% 13% RR 0.24, 95% CI 0.12-0.45, p Neurological worsening 2% 8% RR 0.25, 95% CI 0.11-0.56, p Infections 5% 24% RR 0.20, 95% CI 0.12-0.32, p Uncontrollable pain 5% 15% RR 0.35, 95% CI 0.21-0.59, p Nauseas and vomiting 2% 7% RR 0.32, 95% CI 0.14-0.71, p Bleeding 2% 7% RR 0.34, 95% CI 0.15-0.75%, p Conclusions In our cohort, in patients with an assessment by PCU before the second admission episode, was observed a decrease in number and severity of re-admissions. An optimization of the symptomatic treatment at home implies a decrease in hospital-acquired or nosocomial complications which leads to a reduction in costs and above all, an improvement in the quality life both of patients and their families. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.