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Background Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective treatments for EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC). However, routine clinical practice is different between countries/institutions. Patients and methods The REFLECT study (NCT04031898) is a retrospective medical chart review that explored real-life treatment and outcomes of EGFRm NSCLC patients receiving first-line (1L) first-/second-generation (1G/2G) EGFR TKIs in 8 countries. This study included adult patients with documented advanced/metastatic EGFRm NSCLC with 1L 1G/2G EGFR TKIs initiated between Jan 2015 – Jun 2018. We reviewed data on clinical characteristics, treatments, EGFR/T790M testing patterns, and survival outcomes. Here, we report data from 120 medical charts in 3 study sites from Slovenia. Results The Slovenian cohort (median age 70 years, 74% females) received 37% erlotinib, 32% afatinib, 31% gefitinib. At the time of data collection, 94 (78%) discontinuations of 1L TKI, and 89 (74%) progression events on 1L treatment were reported. Among patients progressing on 1L, 73 (82%) were tested for T790M mutation yielding 50 (68%) positive results, and 62 (85%) received 2L treatment. 82% of patients received osimertinib. Attrition rate between 1L and 2L was 10%. The median (95% CI) real-world progression free survival on 1L EGFR TKIs was 15.6 (12.6, 19.2) months; median overall survival (95% CI) was 28.9 (25.0, 34.3) months. Conclusions This real-world study provides valuable information about 1G/2G EGFR TKIs treatment outcomes and attrition rates in Slovenian EGFRm NSCLC patients. The reduced attrition rate and improved survival outcomes emphasize the importance of 1L treatment decision.

Background Immune checkpoint inhibitors (ICI) are becoming increasingly common in treating several cancer types. Durvalumab is a human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80 and has recently been approved for the treatment of extensive-stage small-cell lung cancer (ES-SCLC) and locally advanced unresectable (NSCLC). The present review aimed to analyse immune-mediated uveitis, secondary to durvalumab treatment, through a review of the literature and a presentation of two clinical cases. Patients and methods A literature review using PubMed search was conducted to identify cases of uveitis secondary to durvalumab and cases of uveitis with optic disc oedema secondary to ICI use that were reported prior to November 14, 2021. Additionally, we report two cases of uveitis consequent on durvalumab treatment. Results Five cases of uveitis secondary to durvalumab use were identified in the literature. Anterior, posterior uveitis and vasculitis were reported. Additionally, we present a case of bilateral intermediate uveitis with bilateral optic disc oedema and a case of bilateral posterior uveitis. Our further search revealed 12 cases of uveitis with optic disc oedema secondary to ICI use, with the majority of cases reported secondary to PD-1 inhibitors. Conclusions Rarely reported, uveitis secondary to durvalumab can present various clinical pictures and requires a thorough diagnostic workup. Once the diagnosis is established, treatment, commonly with a local or systemic corticosteroid, should be adapted to the severity of the inflammation.

Because cancer patients are especially endangered by SARS-CoV-2 infection and have worse disease course and outcomes, it is crucial to protect them from this infection. This study was aimed at assessing protective antibodies after patients received mRNA-based SARS-CoV-2 vaccines. Protective antibodies (e.g., anti-SARS-CoV-2 S1 IgG antibodies) were assessed in patients’ blood before vaccination, after the first and second doses and 3 months after a complete primary course vaccination. Patients’ oncological treatment was unaffected by the vaccination received. The results of protective antibodies were also compared with healthy control subjects who were vaccinated in the same manner. More than 110 cancer patients participated and agreed to have their blood samples analyzed. The rate of antibody production was 96% after a complete primary course of vaccination and was similar with that of healthy control subjects. However, there were some differences noted regarding the oncological treatment that the patients were receiving, with patients who were treated with targeted therapy achieving the highest levels of protective antibodies. Adverse events after vaccination were mostly mild and did not interfere with patients’ general performance. The rate of antibody production for cancer patients after SARS-CoV-2 vaccination is high and similar to that in healthy control subjects but varies with regard to the oncological treatment that patients are receiving. However, antibodies decline substantially after 3 months, and thus a third vaccination is desirable. There were no new safety concerns after vaccination, and most adverse events were mild and short-lived.

Summary Purpose To establish a transborder virtual tumor board (VTB) fostering state-of-the-art management of cancer patients by exchanging knowledge and expertise among oncologists in Central and Southeastern Europe (CEE). Methods We established and implemented a VTB based on the WebEx platform. This allowed for password-protected and secure upload of patient cases to be presented and discussed among colleagues from various oncology centers scattered throughout CEE in order to arrive at a recommendation for further diagnoses and/or treatment. Results A total of 73 cases from 16 oncology centers located in 11 CEE countries were uploaded by 22 physicians; 71 were discussed over the course of 17 virtual meetings between June 2018 and May 2019 and 12 different kinds of malignant diseases were discussed with lung cancer (46.6%), melanoma (19.2%) and bladder cancer (13.6%) being the most commonly presented tumor entities. Of the discussed patients, 93.3% had stage IV disease at the time of presentation, 62.6% received chemotherapy or targeted treatment and 67.1% were treated with immune checkpoint inhibitors (ICPIs). The most common causes for presentation and discussion of patient cases were related to the use of ICPIs (80%). Conclusion When the need for expertise exceeds locally available resources, web-based VTBs provide a feasible way to discuss patient cases and arrive at conclusions regarding diagnoses and/or treatment across large geographic distances. Moreover, VTBs provide an innovative way for proper, state-of-the-art management of patients with malignant diseases in times of social distancing and the resulting need for restricted interaction during the current SARS-CoV‑2 (severe acute respiratory syndrome coronavirus type 2) pandemic.

Background: SARS-CoV-2 vaccination in cancer patients is crucial since they are at increased risk of severe COVID-19 disease course, but data on efficacy and safety of vaccination are scarce.Methods: We performed a prospective observational study of patients with solid cancers on active anticancer treatment (chemotherapy, immunotherapy with immune checkpoint inhibitors (ICI) or targeted therapy) that received mRNA-based SARS-CoV-2 vaccination at two institutions in Slovenia. The immunogenicity was assessed by the detection of anti-SARS-CoV-2 S1 IgG antibodies in serum; patients were sampled before, 2-3 weeks after the first dose, 2-3 weeks after the second dose, and 3 months after the complete primary course of vaccination. The results were also compared to controls, sampled at similar time points.Results: Between March and July 2021 112 patients were included in the analysis. The seroconversion rate in patients without prior COVID-19 infection was 96% after the complete primary course of vaccination with 2 doses, compared to 100% for healthy controls. The seroconversion rate after vaccination for patients on chemotherapy, ICI, and targeted therapy was 100%, 91%, and 97%, respectively. All controls and the majority of patients on chemotherapy and targeted therapy, but only 83% for patients on ICI were adequate responders (anti-SARS-CoV-2 S1 IgG ≥ 880 ng/ml). Three months after the vaccination, a significant drop in antibody levels was observed in patients receiving ICI compared to controls (P < 0.001). Adverse events were mostly mild and predictable, none of the patients experienced serious adverse events after vaccination.Conclusions: Immunogenicity after mRNA-based vaccination against SARS-CoV-2 in cancer patients is only slightly impaired, but influenced by the type of anticancer therapy received. Patients on ICI have the slightest and gradual antibody production. Since antibody levels decline after three months, a third vaccination dose is reasonable to provide adequate protection against severe COVID-19 disease course.The study was approved by the National Ethics Committee (No. 0120-39/2021/6)

e18791 Background: Since cancer patients (pts) are at increased risk of severe morbidity and mortality due to COVID-19, SARS-CoV-2 vaccination is crucial to prevent severe disease course. The efficacy and longevity of vaccine protection, however, is still in question. Methods: In this prospective observational study we assessed immunogenicity of cancers patients on active treatment for solid cancers in two Slovenian Oncology Centres receiving SARS-CoV-2 vaccine by detection of anti-SARS-CoV-2 S1 IgG antibodies in serum; before, after first and second dose, 3 and 6 months (mo) after complete primary course of vaccination and 1 mo after the 3rd booster dose. Samples with ≥ 175 ng/ml were considered positive. Results: There were 125 pts included in the study, 112 completed the primary course of vaccination with 2 vaccine doses and 34 received the booster 3rd dose. Out of 34 pts receiving booster 3rd dose, the majority received mRNA based vaccines (88%) for the primary course of vaccination and all patients received mRNA based vaccines for the booster 3rd dose. Median time from 2nd to booster 3rd dose of vaccine was 6.75 mo, median age of pts was 66 yrs and 59% were male. Patients were receiving chemotherapy (ChT), immune checkpoint inhibitors (IO) or targeted therapy (TT) in 9%, 56% and 35%, respectively. They achieved seroconversion in 94% after the 2nd and in 97% after the 3rd booster dose. Overall, the median anti-SARS-CoV-2 S1 IgG titer was 11,191 ng/ml (mean 25,394; range 0 – 100,000) after complete primary course of vaccination and 1892 ng/ml (mean 6413; range 0 – 72,000) 6 mo after, P < 0.0001. However anti-SARS-CoV-2 S1 IgG antibodies increased significantly after the 3rd booster dose with median antibody value 51,310 ng/ml (mean 51,787; range 0 – 100,000), P < 0.001. Only one pt in this group got infected with SARS-CoV-2 and had a mild disease course. Conclusions: Cancer pts treated for solid malignancies achieve a high rate of seroconversion through the primary course of vaccination. However, significant waning of immunity against SARS-CoV-2 is observed 6 months thereafter, which can be potentiated with additional 3rd booster dose of vaccine.

Brain metastases (BrMs) are associated with significant morbidity and are found in up to 50% of patients with advanced non-small cell lung cancer (NSCLC). Most of the literature focuses on symptomatic BrMs, with a lack of baseline brain imaging in asymptomatic patients. Unfortunately, much of the data on local treatments with or without systemic treatment is retrospective. Clinical trials of systemic treatments largely exclude patients with BrMs. Chemotherapy is an active treatment for BrM with response rates in the brain similar to other sites of disease. Targeted systemic treatments in patients with driver mutations (EGFR and ALK-MET to date) have impressive central nervous system (CNS) penetrance and response rates. Unfortunately, no prospective data can currently guide the timings or modality of local therapies with systemic treatments in these patients who have a high incidence of CNS disease, but retrospective data suggest that early local therapies may give better intracranial progression-free survival (ICPFS). Recent immunotherapy trials have included patients with BrMs. These patients have largely been pre-treated with local therapies and are asymptomatic. Thus, the current standard is becoming, early local therapies before or in conjunction with immunotherapy agents. The approach seems to be safe. Prospective studies are needed in NSCLC BrMs patients to make sure any benefit from local therapies on the ICPFS and quality of life is not overlooked. Here we report what we think are reasonable conclusions from the available data and make suggestions for future clinical trials in the management of NSCLC BrMs.

PURPOSE: Burnout is defined as a three-dimensional syndrome—emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA)—caused by chronic occupational stress. The aim of the current study was to investigate the prevalence of burnout among oncologists in Eastern Europe and to identify the contributing factors. METHODS: The study was conducted as an online survey between October 2017 and March 2018. Oncologists (including medical, radiation, clinical, and surgical oncologists) from 19 countries were invited to participate. The survey consisted of 30 questions, including the standardized burnout instrument, Maslach Burnout Inventory, and eight demographic questions. Burnout risk was scored according to the scoring manual for health care workers. RESULTS: The study included 637 oncologists. Overall, 28% were at low or intermediate risk and 72% were at high risk for burnout. Forty-four percent of participants were at high risk for EE, 28.7% for DP, and 47.3% for PA. EE risk was associated with female sex. DP risk was highest among clinical and radiation oncologists, whereas PA risk was positively correlated with years of service, percentage of cancer deaths, and availability of the number of oncologists. In multivariate logistic regression analysis, burnout was significantly associated with standardized cancer mortality and fewer years of practice. CONCLUSION: Burnout among oncologists in Eastern Europe is high, and younger oncologists are the most vulnerable group. Preventive measures should be taken to address this issue, which negatively affects optimal care delivery and poses a threat to oncologists’ health and well-being.

Objectives: Timely access to novel anticancer drugs is challenging and value frameworks such as the European Society of Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) could assist...

BackgroundWith introduction of immunotherapy (IT) into the treatment of advanced non-small-cell lung cancer (NSCLC), a need for predictive biomarker became apparent. Programmed death ligand 1 (PD-L1) protein expression is most widely explored predictive marker for response to IT. We assessed PD-L1 expression in tumor cells (TC) and immune cells (IC) of squamous-cell carcinoma (SCC) and adenocarcinoma (AC) patients.Patients and methodsWe obtained 54 surgically resected tumor specimens and assessed PD-L1 expression by immunohistochemistry after staining them with antibody SP142 (Ventana, USA). Clinicopathological characteristics were acquired from the hospital registry database. Results were analyzed according to cut-off values of ≥ 5% and ≥ 10% of PD-L1 expression on either TC or IC.Results29 (54%) samples were AC and 25 (46%) were SCC. PD-L1 expression was significantly higher in TC of SCC compared to AC at both cut-off values (52% vs. 17%, p = 0.016 and 52% vs. 14%, p = 0.007, respectively) no difference in PD-L1 expression in IC of SCC and AC was found. In AC alone, PD-L1 expression was significantly higher in IC compared to TC at both cut-off values (72% vs. 17%, p < 0.001 and 41% vs. 14%, p = 0.008, respectively), while no significant difference between IC and TC PD-L1 expression was revealed in SCC.ConclusionsOur results suggest a significantly higher PD-L1 expression in TC of SCC compared to AC, regardless of the cut-off value. PD-L1 expression in IC is high in both histological subtypes of NSCLC, and adds significantly to the overall positivity of AC but not SCC.

9086 Background: Brain metastases (BM) frequently occur in patients (pts) with epidermal growth factor receptor mutated non-small cell lung cancer (EGFRm NSCLC) and represent a poor prognostic marker. This study aimed to describe the clinical characteristics, treatment patterns and survival outcomes in EGFRm NSCLC pts treated with 1st or 2nd generation tyrosine-kinases inhibitors (TKIs) in first-line (1L). Methods: The retrospective real-world study REFLECT (NCT04031898) collected data from 896 pts initiating 1L TKI between 1 January 2015-30 June 2018 in Europe and Israel. Descriptive statistics were used to assess demographic and clinical characteristics in subgroups of patients with and without BM. Kaplan-Meier methods were used to estimate median real world progression free survival (mPFS) and overall survival (mOS) from start of 1L. Results: Out of 896 pts, 198 (22.1%) had BM at start of 1L, 134 (15%) developed BM later (any time), and 564 (62.9%) had no sign of BM at the time of data collection. Among pts who later developed BM the median time between the start of 1L and first diagnosis of BM was 13.5 months. Median duration of follow-up was 21.5 months. Of 332 pts with BM at any time 64.2% were female, similar to the ratio in pts without BM (64.0%). At diagnosis, median age was 65 years in pts with BM vs. 70 in those who never developed BM. Of pts with BM at any time, 50.9% had exon 19 deletion, 30.4% L858R point mutation and 18.7 % uncommon EGFR mutations at baseline, compared to 56.6%, 31.7% and 11.7% in pts without BM, respectively. At data collection, 94.9% of the pts with BM at diagnosis had progressed compared to 79.8% among those with no BM. Overall, whole brain radiation was the most frequently used treatment for BM (31.0%) followed by stereotactic radiosurgery (18.1%) and targeted therapies (13.3%). T790M testing rates were highest among pts developing BM later (85.7%) and lowest among those with BM from start (66.1%). The T790M positivity rate was highest in pts developing BM later (65.7%) and lowest among those with BM from start (50.4%). More pts received osimertinib in later lines among those with BM at any time compared to those without BM (51.3% vs 43.8%). Median real world PFS and OS (95% CI) were shorter among pts with BM at baseline compared to those never developing BM: 10.2 (8.8, 11.5) vs 15.2 (13.7, 16.1) months, and 19.4 (17.1, 22.1) vs 30.3 (27.1, 33.8) months, respectively. At the time of data collection, 77.3% of pts with BM at baseline were deceased compared to 52.5% pts with no BM. Conclusions: More than one third of pts included in REFLECT had BM at any time. Uncommon EGFR variants at baseline were observed more frequently in pts with BM. mPFS and mOS were shorter in pts with BM at baseline compared to those never developing BM. These data highlight the need for improved treatment and CNS control in pts with EGFRm NSCLC. Clinical trial information: NCT04031898.

Introduction: For epidermal growth factor receptor mutation-positive (EGFRm) non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred first-line (1 L) treatment in the advanced setting. Osimertinib, a third-generation EGFR-TKI, received full approval in 2017 for second-line (2 L) treatment of EGFR T790M-positive NSCLC. The REFLECT study characterizes real-world treatment/testing patterns, attrition rates, and outcomes in patients with EGFRm advanced NSCLC treated with 1 L first-/second-generation (1G/2G) EGFR-TKIs before 1 L osimertinib approval. Methods: Retrospective chart review (NCT04031898) of European/Israeli adults with EGFRm unresectable locally advanced/metastatic NSCLC, initiating 1 L 1G/2G EGFR-TKIs 01/01/15–30/06/18 (index date). Results: In 896 patients (median follow-up of 21.5 months), the most frequently initiated 1 L EGFR-TKI was afatinib (45%). Disease progression was reported in 81%, including 10% (86/896) who died at 1 L. By the end of study, most patients discontinued 1 L (85%), of whom 33% did not receive 2 L therapy. From index, median 1 L real-world progression-free survival was 13.0 (95% confidence interval (CI): 12.3–14.1) months; median overall survival (OS) was 26.2 (95% CI: 23.6–28.4) months. 71% of patients with 1 L progression were tested for T790M; 58% were positive. Of those with T790M, 95% received osimertinib in 2 L or later. Central nervous system (CNS) metastases were recorded in 22% at index, and 15% developed CNS metastases during treatment (median time from index 13.5 months). Median OS was 19.4 months (95% CI: 17.1–22.1) in patients with CNS metastases at index, 24.8 months (95% CIs not available) with CNS metastases diagnosed during treatment, and 30.3 months (95% CI: 27.1, 33.8) with no CNS metastases recorded. Conclusion: REFLECT is a large real-world study describing treatment patterns prior to 1 L osimertinib availability for EGFRm advanced NSCLC. Given the attrition rates highlighted in the study and the impact of CNS progression on outcomes, offering a 1 L EGFR-TKI with CNS penetration may improve patient outcomes in this treatment setting.