Background We report for the first time the molecular landscape and outcome associations from the prospective CLIMEDIN trial in Greece. Methods Two hundred patients with newly diagnosed advanced NSCLC (March 2022–October 2023) were enrolled and randomized to standard-of-care education versus additional automated, adverse-event–targeted digital interventions. Within this study baseline testing (EGFR, ALK, PD-L1) was performed in all; 165 tumors underwent comprehensive NGS (Oncomine Comprehensive Assay v3). Primary endpoint was improvement in AEs/QoL; secondary endpoints included ORR, PFS and OS. Associations between genomic alterations and outcomes were explored. Results Median age was 68 years; 75% male; 52% current smokers; adenocarcinoma 68.5%. Most received chemo-immunotherapy (66%). At data cut-off (December 2025; reverse-Kaplan–Meier median follow-up 36.3 months), median PFS was 9.6 months and median OS was 15.2 months. Across 200 tumors, 495 pathogenic variants (PVs) were identified in 83 genes. Exploratory outcome analyses showed longer OS in EGFR-mutant disease (preserved under parsimonious multivariable adjustment) and a formal KRAS × smoking interaction for OS (interaction P = 0.011). Conclusions In this cohort, the molecular profile mirrors other Caucasian series, with clinically relevant enrichment patterns for EGFR and KRAS. ECOG performance status and first line treatment were the dominant prognostic factors in this cohort. A novel KRAS and smoking interaction for overall survival warrants prospective validation.

PURPOSEThis trial aims to investigate the effectiveness of online digital intervention in patients with non-small cell lung cancer (NSCLC) in terms of adverse events (AEs) and quality of life (QoL). METHODSThis randomized trial recruited 200 patients with advanced NSCLC (March 2022-October 2023). All patients received standard-of-care precise treatment, predominantly immunochemotherapy. The study was designed to assess AEs and QoL improvement. Through the CareAcross online platform, all patients received information about their disease and treatment and reported any of the 22 predefined AEs at any time. Patients were randomly assigned 1:1 in the intervention (A) and control (B) arm; patients in arm A automatically received, additionally, evidence-based guidance for the reported AEs. EuroQol 5-dimension 5-level responses were collected at baseline and at each treatment cycle. Resulting scores were compared between baseline and after the sixth cycle. In addition, patient case-level hospitalization data were collected and costs were estimated based on reimbursed costs as defined by the Ministry of Health, enabling a post hoc analysis. RESULTSClinical characteristics were well-balanced. More AEs were reported by patients online versus to their clinicians (P < .01). Among the 22 AEs, 17 improved more in arm A, with the improvement in rash and stomatitis being statistically significant. In QoL, there was no improvement in any of the five EuroQol 5-Dimension dimensions. Digital intervention was cost-saving with lower mean costs for hospitalization (P < .001). Overall response rate, progression-free survival, and overall survival were not statistically different between the two arms, ensuring comparable clinical outcome. CONCLUSIONDigital oncology tends to improve selected AEs and is cost saving. Patients report, digitally, more informative AEs. Digital oncology can be a complementary tool to the oncology team and warrants further exploration.

e23271 Background: CLIMEDIN was a randomized controlled trial of digital support for patients with advanced or metastatic non-small cell lung cancer. Patients received either general adverse event (AE) information (control arm), or personalized support depending on their reported AEs (intervention arm). Given the statistically significant difference found between the AEs reported digitally by patients and those captured directly by clinicians, this post-hoc analysis aims to identify patterns of likely co-occurrence of AEs. Methods: Between March 2022 and December 2024, 188 patients submitted 7046 reports among 22 preselected AEs, captured in the CareAcross platform database. For this analysis these reports were de-identified and structured based on the specific AEs they contained. Association rule mining (apriori algorithm with support thresholds) was used to calculate the conditional probability of an AE subset (“Associated AEs”) being reported given that another subset (“Index AEs”) was reported concurrently. Results: The analysis resulted in 7846 pairs of Associated & Index AE subsets, with up to 7 AEs per subset. The conditional probability of co-occurrence (“Confidence”) ranged from 2.5% to 100%.To make the patterns clinically meaningful and practical, analyses were restricted to subsets of 1-2 AEs, resulting in 1870 combinations. Keeping the pairs with probability > = 80% resulted in 110 records (37 of which with > = 90% probability).The majority (78/110 or 71%) of Associated AEs included Fatigue.Among the AEs that are not immediately available upon clinical examination: Anorexia was correlated with combinations containing dyspnea (with any of rash, constipation, dysphagia, dysgeusia, diarrhea) as well as dysphagia & weight loss. Dysgeusia was correlated with combinations containing anorexia (with any of pruritus, diarrhea), diarrhea (with any of cough, anorexia, dry skin), stomatitis (with any of dry skin, cough) and more.The full list of associations is available upon request.The Table contains the most frequently occurring pairs of 1 or 2 AEs that do not include Fatigue. Conclusions: Analysis of Patient-Reported Outcomes can provide relevant Real World Evidence to support clinicians in completing the view of their patients’ journeys. This can be particularly applicable when information is missing, or AEs cannot be readily evaluated clinically.Data Science and Artificial Intelligence can further help derive actionable insights for clinical care and research. Clinical trial information: 05372081 . Index AEs Associated AEs Confidence (%) Peripheral Neuropathy, Chest Pain Dry Skin 94.7 Dyspnea, Rash Anorexia 93.7 Peripheral Neuropathy, Bone Pain Dry Skin 92.1 Anorexia, Pruritus Dysgeusia 88.7 Peripheral Neuropathy, Chest Pain Bone Pain 88.4 Cough, Diarrhea Dysgeusia 88.2 Weight Loss, Dysphagia Anorexia 88.1 Cough, Diarrhea Dry Skin 87.5 Dyspnea, Rash Dysgeusia, Anorexia 86.3

Abstract Background: Co-mutations, PD-L1 and TILs are key NSCLC biomarkers. We applied deep learning to a multimodal patient cohort to identify prognostic patterns integrating morphology, mutations, and clinical features. Methods: 367 NSCLC patients from 18 Hellenic Cooperative Oncology Group-affiliated centers were retrospectively assessed for PD-L1 status (Dako 22C3 pharmDx), TILs (H&E slides), and somatic pathogenic variants with a 38-gene next-generation sequencing (NGS) panel. Whole slide images (WSI) were digitized by an optical microscope scanner. Ten pathology foundation models were benchmarked for predicting mutation, co-mutation, PD-L1 and TILs status. Mutated genes with >5% prevalence were considered for mutation and co-mutation endpoints (TP53, KRAS, STK11, PTEN, EGFR). A vision transformer model was trained on WSI features to predict endpoints and evaluate AUROC. Kaplan-Meier analysis assessed prognostic relevance of models and top feature tiles from model attention maps provided morphological explainability. The STAMP digital pathology pipeline supported feature extraction and model training. Results: Single mutation models yielded AUROC scores of 0.6-0.85, with STK11 prediction from HOptimus1 features highest. Co-mutation models produced AUROC scores of 0.69-0.77 with EGFR-TP53 prediction from Uni2 features the best. The KRAS-TP53 co-mutation model (AUROC 0.69, Uni2) showed significant separation in overall survival curves (p=0.05) between classes. Best-performing PD-L1 and TIL models also demonstrated significant survival separation (p=0.005 and p=0.05). Conclusion: Findings demonstrate the potential of pathology foundation models to derive complex clinically-relevant prognostic models for NSCLC with multimodal explainability. Citation Format: Sanddhya Jayabalan, Konstantinos Efthymiadis, Alexia Eliades, Kyriaki Papadopoulou, Abraham Pouliakis, Elena Fountzilas, Sofia Lampaki, Mattheos Bobos, Anna Goussia, Soultana Meditskou, Konstantinos Kyritsis, Helena Linardou, George Pentheroudakis, Dimitrios Bafaloukos, Dimitrios Pectasides, Epaminondas Samantas, Zunamys I. Carrero, George Fountzilas, Jakob N. Kather. Deep learning integration of molecular and histopathological data for prognostic stratification in non small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1448.

Background/Objectives: The aim of the study was to evaluate the real-world effectiveness of immunotherapy compared to chemotherapy in advanced non-small-cell lung cancer (NSCLC) and assess molecular profiling patterns in a large Greek cohort. Methods: This was a retrospective study of patients with advanced NSCLC from three oncology centers. Clinical, pathological, and/or molecular data were collected from the patient medical records. The primary endpoint was overall survival (OS). Results: Overall, 684 patients with advanced NSCLC were included; median age 67 years (range, 33 to 89). More than half of the patients (406, 59.4%) had been diagnosed with de novo metastatic disease. Overall, 289 of 684 (42.3%) patients underwent tumor molecular profiling. Immunotherapy use, with or without chemotherapy, in the first-line setting increased significantly over time (p < 0.001). Among 610 patients eligible for outcome analysis, immunotherapy at any line of treatment was associated with increased OS compared to chemotherapy alone (17.5 vs. 8.6 months; HR: 0.51, 95% CI: 0.42, 0.61; p < 0.001). The results remained consistent with the primary analysis as well as the landmark analysis using a 3-month cutoff to account for the immortal-time bias. Furthermore, time to next treatment (TTNT) was significantly longer with immunotherapy use in both first- and second-line treatment (TTNT1: 10.0 vs. 6.8 months, HR: 0.45, 95% CI: 0.34, 0.58; p < 0.001; TTNT2: 6.7 vs. 5.9 months, HR: 0.59, 95% CI: 0.40, 0.87; p = 0.009). Immunotherapy use remained an independent predictor of improved survival (HR: 0.50, 95% CI: 0.40, 0.63; p < 0.001). Conclusions: Immunotherapy, with or without chemotherapy, significantly improved clinical outcomes compared to chemotherapy alone in a real-world cohort of patients with advanced NSCLC. While molecular testing rates increased significantly over the study, only a minority of patients underwent PD-L1 testing, while broad molecular profiling was also incomplete, limiting the interpretation of treatment effects. Improvements to guarantee the universal molecular testing of patients with NSCLC are warranted.

OBJECTIVE:This study aimed to assess the cost-effectiveness of lung cancer screening (LCS) employing volume-based low-dose computed tomography (LDCT) in contrast to the absence of screening, targeting an asymptomatic high-risk population in Greece, leveraging the outcomes derived from the NELSON study, the largest European randomized control trial dedicated to LCS. METHODS:A validated model incorporating a decision tree and an integrated state-transition Markov model was used to simulate the identification, diagnosis, and treatments for a population at high risk of developing lung cancer, from a healthcare payer perspective. Screen-detected lung cancers, costs, life years (LYs), quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were predicted. Sensitivity and scenario analyses were conducted to assess the robustness and reliability of the model's outcomes under varying parameters and hypothetical situations. RESULTS:Annual LCS with volume-based LDCT detected 17,104 more lung cancer patients at early-stage among 207,885 screening population, leading to 8,761 premature lung cancer deaths averted. In addition, in contrast to no screening, LCS yielded 86,207 LYs gained and 50,207 incremental QALYs at an additional cost of €278,971,940, resulting in an ICER of €3,236 per LY and €5,505 per QALY, over a lifetime horizon. These estimates were robust in sensitivity analyses. CONCLUSIONS:LCS with volume-based LDCT, targeting an asymptomatic high-risk population, is highly cost-effective in Greece. Implementing LCS ensures efficient allocation of public healthcare resources while delivering substantial clinical benefits to lung cancer patients.

BackgroundThe treatment landscape of non-metastatic non-small cell lung cancer (NM-NSCLC) is rapidly evolving with recent approvals of immunotherapies and targeted therapies.MethodsThis retrospective study included 202 adults diagnosed with NM-NSCLC between 1 January 2018 and 31 December 2020 primarily aiming to capture initial management strategies.ResultsMost frequent treatment patterns among Stage I/II patients (N = 84) were surgery only (48.8%) and surgery with adjuvant chemotherapy (with/without RT; 42.9%). Among Stage III patients (N = 118), most frequent patterns were chemotherapy plus radiotherapy (44.9%) and chemotherapy only (18.6%); 58.6% of Stage IIIA patients underwent surgery (of these, 32.4% also received chemotherapy and radiotherapy).ConclusionInitial strategy was aligned with contemporary at that time European guidelines, setting a benchmark for understanding the future uptake of new therapies.

1515 Background: This trial aims to investigate the feasibility and effectiveness of online digital intervention to NSCLC patients in terms of adverse events (AEs), quality of life (QoL), cost, and the interrelation with clinical and molecular characteristics. Methods: This prospective randomized trial recruited 200 advanced NSCLC patients (3/22-10/23). Final analysis was undertaken in 12/24. All had NGS tissue analysis for 161 genes, and received standard treatment (predominantly immuno-chemotherapy). Through the CareAcross online platform, they received information about their disease and treatment, and periodically reported any of the 22 preplanned AEs. Patients were randomized 1:1 in the Intervention (A) and Control (B) arm; patients in arm A received digitally, additionally, evidence-based guidance for the reported AEs. The study was designed to assess AE improvement (measured per patient as reduction of AEs reported at last contact, compared to those previously reported) and QoL. EQ5D-5L scores were collected. Patient-case level hospitalization data were collected and costs were estimated based on reimbursed cost as defined by the Ministry of Health. Results were correlated with patients’ clinical and molecular characteristics. Results: Clinical and molecular characteristics will be presented during ASCO Congress. Comparing arms A vs B: ORR: 42.1% vs 41.7%; Median PFS: 11m (8.0-15) vs 10m (7.0-13), 1-year PFS: 43% (31%-54%) vs 42% (31%-53%) (p = 0.4). Median OS: 15m (12-20) vs 16m (12-21), 1-year OS: 59% (48%-68%) for both arms (p = 0.9). PFS and OS were improved for those with best responses (p < 0.001). Patients with EGFR mutations had better OS (p = 0.05). The most common AEs reported in both arms were fatigue, cough, anorexia, nausea. More AEs were reported online vs to clinicians (89% vs 68% of patients; p < 0.01). Baseline EQ5D-5L was similar for both arms; when compared with data at best response, Anxiety/Depression showed the biggest difference in improvement for arm A vs B. Among the 22 ΑEs, 17 improved more in arm A, 1 improved equally, and 4 improved more in Arm B. The comparative improvements of rash and stomatitis in arm A vs B were statistically significant (p = 0.0073 & p = 0.0447). The mean hospitalization cost (arm A vs B, in Euros) was 455.4 (95%CI: 91.9-941.5) vs 779.5 (346.6-1328.5) (p < 0.001); the mean diagnostics cost was 20.3 (0.5-50.8) vs 73.3 (1.3-186.1) (p < 0.001). Conclusions: Digital oncology is feasible, cost-effective by reducing hospitalizations and tends to improve QoL (especially anxiety and depression) and most AEs of NSCLC patients regardless of clinical and molecular status. Patients report, digitally, more informative AEs for clinical and research analysis. Through the digital transformation of healthcare, digital oncology can be a complementary tool to the Oncology team and warrants further exploration. Clinical trial information: NCT05372081 .

1520 Background: The purpose of this trial is to investigate the effectiveness of online digital intervention to NSCLC patients in terms of quality of life (QoL), cost and the interrelation with clinical and molecular characteristics. Methods: This prospective randomized trial recruited 200 advanced NSCLC patients (3/22-10/23). All had NGS tissue analysis for 161 genes and received standard treatment (predominantly immuno-chemotherapy). Through the CareAcross online platform they received information about their disease and treatment, and periodically reported any of 22 preplanned adverse events (AEs). Patients were randomized 1:1 in the intervention (A) and control (B) arm; patients in arm A received digitally, additionally, evidence-based guidance for the reported AEs. The study was designed to assess QoL improvement (measured per patient as reduction of the number of AEs reported at last contact, compared to those previously reported). EQ5D-5L scores were collected. Patient-case level hospitalizations data were collected and costs were estimated based on reimbursed costs as defined by the Ministry of Health. Results were correlated with patients’ clinical and molecular characteristics. Results: Clinical and molecular characteristics will be presented during ASCO Congress. For all patients, responses were: CR: 2%, PR: 35.5%, SD: 35%, PD: 10.5%. Median PFS was 7.0 months (95%CI: 5-8), 1-year 18% (38%-55%). Median OS: 12 months (11-14), 1-year 47% (38%-55%). No difference was found between the two arms in any of the above, nor in OS in relation to clinical and molecular characteristics. The most common AEs that patients reported were fatigue, cough, anorexia, nausea. More patients submitted AE reports online than their clinicians (89% vs 68% of patients, p<0.01); more AEs were reported per submission, compared to their clinicians. Patients in arm Α reported marginally higher improvement compared to B (77.2% vs 75.7%); 15 of 22 AEs were associated with higher (14) or same (1) improvement in arm A vs B (not statistically significant); of the most common: fatigue (61.3% vs 48.6%), anorexia (86.5% vs 70.2%; p<0.05) and nausea (93.0% vs 87.2%). Baseline EQ5D was similar in both arms; comparing post-treatment (6th cycle) results shows higher improvement in all 5 dimensions in arm A vs B, especially in Anxiety/Depression (final values: 1.9 vs 2.2). The mean AE-related costs in Euros in arm A vs B were: hospitalization: 455.4 (95%CI: 91.9-941.5) vs 779.5 (346.6-1328.5) (p<0.001); diagnostics: 20.3 (0.5-50.8) vs 73.3 (1.3-186.1) (p<0.001). Follow up is ongoing. Conclusions: Digital oncology is feasible, cost-effective by reducing hospitalizations, improves certain AEs and tends to improve QoL of NSCLC patients regardless of clinical and molecular status. Patients report digitally more informative AEs for clinical and research analysis. Online platforms can complement the Oncology team. Clinical trial information: NCT05372081 .

Lung cancer is a leading cause of cancer-related deaths globally, includes small cell lung cancer (SCLC), characterized by its aggressive nature and advanced disease at diagnosis. However, the identification of reliable biomarkers for SCLC has proven challenging, as no consistent predictive biomarker has been established. Nonetheless, certain tumor-associated antigens, including programmed death-ligand 1 (PDL1) and Delta-Like Ligand 3 (DLL3), show promise for targeted antibody-based immunotherapy. To ensure optimal patient selection, it remains crucial to comprehend the relationship between PDL1 and DLL3 expression and clinicopathological characteristics in SCLC. In this study, we investigated the expression patterns of PDL1 and DLL3 biomarkers in endobronchial samples from 44 SCLC patients, examining their association with clinical characteristics and survival. High PDL1 expression (>1%) was observed in 14% of patients, while the majority the SCLC patients (73%) exhibited high DLL3 expression (>75%). Notably, we found a positive correlation between high PDL1 expression (>1%) and overall survival. However, we did not observe any significant differences in the biomarkers expression concerning age, sex, disease status, smoking status, or distant metastases. Further subgroup analysis revealed that a high co-expression of both PDL1 (>1%) and DLL3 (100%) antigens was associated with improved overall survival. This suggests that SCLC expressing PDL1 and DLL3 antigens may exhibit increased sensitivity to therapy, indicating their potential as therapeutic targets. Thus, our findings provide novel insights into the simultaneous evaluation of PDL1 and DLL3 biomarkers in SCLC patients. These insights have significant clinical implications for therapeutic strategies, survival prediction, and development of combination immunotherapies.

Background/Aim: Nivolumab is an FDA-approved immune checkpoint inhibitor (ICI) for patients with advanced, pre-treated non-small cell lung cancer (NSCLC). However, treatment profiles and patient outcomes often differ in routine clinical practice while the financial impact of approved therapies is largely unknown. In this study, we investigated the efficacy, tolerability, and economic impact of nivolumab in real-world settings (RWS) in Greece. Patients and Methods: Patients diagnosed with advanced pre-treated NSCLC, receiving nivolumab were recruited from October 2015 until November 2019 across 18 different clinical centers in Greece. Endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. Cost analysis was conducted using a third-party public-payer perspective (National Organization for Healthcare Services Provision; EOPYY). Results: A total of 346 patients, median age 66.5 years, were included. With 43.4 months median follow-up, median PFS was 7.8 months and median OS 15.8 months. The 1-year OS rate was 56.5%, 2-year OS 38.8%, and 3-year OS 27.3%. The ORR was 29.5% and DCR 58.7%, with a median response duration of 26.8 months. Patients with objective response were more likely to experience long-term survival (HR=0.14, p<0.001). Only 8.4% of patients experienced grade 3-4 adverse events. The presence of immune-related adverse events was associated with improved OS (HR=0.77, p=0.043). Nivolumab-associated economic burden accounted for €2,214.10 per cycle for each patient, mainly attributed to drug-acquisition costs. Conclusion: This is the first report of real-world efficacy, safety, and economic burden of nivolumab in pre-treated patients with NSCLC in Greece. Indirectly compared to clinical trials, nivolumab was associated with improved efficacy in RWS, further supporting its use in clinical practice and providing insights on clinical prognosticators. The main cost component affecting the nivolumab economic burden was drug-acquisition costs, while toxicity-associated cost was negligible.

Background/Aim: Real-world data on the EGFR mutational profile upon progression after first/second-generation EGFR-TKI treatment in patients with advanced non-small-cell lung cancer (NSCLC) and treatment strategies employed thereon are needed. Patients and Methods: This observational study was conducted in 23 hospital-based lung cancer Centers in Greece (protocol code: D133FR00126). Ninety-six eligible patients were consecutively enrolled between July-2017 and September-2019. Re-biopsy was performed in 18 of 79 patients who tested T790M-negative in liquid biopsy after progression in the first-line (1L) setting. Results: Of the study population, 21.9% tested T790M-positive, while 72.9% proceeded to 2L treatment, mainly comprising of a third -generation EGFR-TKI (48.6%), a switch to chemotherapy (30.0%), or chemo-immunotherapy (17.1%). The objective response rate (ORR) in 2L was 27.9% in T790M-negative and 50.0% in T790M-positive patients. Of evaluable patients, 67.2% experienced disease progression; median progression -free survival (PFS) was 5.7 and 10.0 months among T790M-negative and positive patients, respectively. Among T790M-negative patients, longer median PFS and post-progression survival were observed with third-generation EGFR-TKI treatment. Conclusion: Mutational status and treatment strategy were identified as critical determinants of clinical outcomes in the 2L-setting of EGFR-mutated NSCLC patients in real-world settings in Greece, with early diagnosis, appropriate molecular testing and high-efficacy treatments at first lines positively affecting ORR and PFS.

Introduction: Real-world evidence regarding molecular epidemiology and management patterns of patients with EGFR exon-20 mutated, advanced NSCLC outside the context of clinical trials is lacking.Methods: We created a European registry for patients with advanced EGFR exon 20-mutant NSCLC diagnosed from January 2019 to December 2021. Patients enrolled in clinical trials were excluded. Clinicopathologic and molecular epidemiology data were collected, and treatment patterns were recorded. Clinical end points according to treatment assignment were assessed using Kaplan-Meier curves and Cox regression models.Results: Data on 175 patients from 33 centers across nine countries were included in the final analysis. Median age was 64.0 (range: 29.7-87.8) years. Main features included female sex (56.3%), never or past smokers (76.0%), adenocarcinoma (95.4%), and tropism for bone (47.4%) and brain (32.0%) metastases. Mean programmed death-ligand 1 tumor proportional score was 15.8% (range: 0%-95%) and mean tumor mutational burden was 7.06 (range: 0-18.8) mutations per megabase. Exon 20 was detected in the tissue (90.7%), plasma (8.7%), or both (0.6%), using mostly targeted next-generation sequencing (64.0%) or polymerase chain reaction (26.0%). Mutations were mainly insertions (59.3%), followed by duplications (28.1%), deletions-insertions (7.7%), and the T790M (4.5%). Insertions and duplications were located mainly in the near loop (codons 767-771, 83.1%) and the far loop (codons 771-775, 13%) and only in 3.9% within the C helix (codons 761-766). Main co-alterations included mutations in TP53 (61.8%) and MET amplifications (9.4%). Treatment on mutation identification included chemotherapy (CT) (33.8%), CT-immunotherapy (IO) (18.2%), osimertinib (22.1%), poziotinib (9.1%), mobocertinib (6.5%), mono-IO (3.9%), and amivantamab (1.3%). Disease control rates were 66.2% with CT plus or minus IO, 55.8% with osi-mertinib, 64.8% with poziotinib, and 76.9% with mobo-certinib. Corresponding median overall survival was 19.7, 15.9, 9.2, and 22.4 months, respectively. In multivariate analysis, type of treatment (new targeted agents versus CT +/- IO) affected progression-free survival (p = 0.051) and overall survival (p = 0.03).Conclusions: EXOTIC represents the largest academic real -world evidence data set on EGFR exon 20-mutant NSCLC in Europe. Indirectly compared, treatment with new exon 20 -targeting agents is likely to confer survival benefit than CT plus or minus IO.(c) 2022 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND li-cense (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Aim: To retrospectively characterize real-world therapeutic strategies, clinical outcomes and attrition rates with EGFR tyrosine kinase inhibitors (TKIs), before first-line osimertinib approval, in EGFR-mutated advanced/metastatic non-small-cell lung cancer patients in Greece. Results: Among 160 patients, the discontinuation rate for first-line first- or second-generation EGFR-TKIs was 85%; among these patients, 43% did not receive any second-line therapy and 9.4% died during an 18.7-month follow-up period. Median progression-free and overall survival were 12.1 and 20.9 months, respectively. Osimertinib was offered as second- and third-line treatment in 69.6 and 21.7% of patients with the T790M mutation, respectively. Brain metastases were recorded in 10.6% of patients during treatment, with median overall survival of 4.9 months. Conclusion: Given the high attrition rates and the impact of CNS progression, offering the most appropriate first-line EGFR-TKI treatment with CNS penetration is key to maximize outcomes.

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line option for patients with advanced, EGFR-mutant non-small cell lung cancer (NSCLC). Afatinib, a second-generation irreversible EGFR-TKI, has been exten-sively used in Greece in this setting; however, real-world data regarding molecular epide-miology and financial implications of afatinib use are lacking. Materials and Methods: This was an observational, non-interventional, multicenter, retro-spective cohort study, based on real-world data collected from the medical charts/records of patients treated with afatinib between 15/03/2015 and 25/06/2020 and were recorded on a web-based data capture system. Cox models were used to assess the prognostic significance of clinicopathological parameters with respect to clinical outcomes of interest. Cost analysis was conducted from a public third-payer perspective, and only direct medical costs reim-bursed by the payer were considered. Results: A total of 59 patients were treated with afatinib for their EGFR mutation-positive advanced NSCLC; the median age was 61 years (range: 37-91). Performance status was zero in 61%, and brain metastases were present in 13.6%. Forty-four patients (74.6%) had a deletion in exon 19 only, while nine (15.3%) had a mutation in exon 21, 8 of them in L858R and one in L861Q. At a median follow-up of 41.8 months (95% CI 35.9-51.4), the median PFS was 14.3 months (95% CI 12.2-16.4), and the median OS was 29 months (95% CI 25.6-33.4). Corresponding values for patients with deletion 19 only were 14.3 months (95% CI 11.5-18.5) and 28.1 months (95% CI 21.1-32.6), respectively. The mean expendi-ture for the treatment of each patient equals euro 25,333.68; with euro 21,865.06 being attributed to drug acquisition costs, euro 3325.35 to monitoring costs and euro 143.27 to adverse event treatment-related costs. Conclusion: Long-term data in the real-world setting in Greece confirm activity, tolerability and cost-effectiveness of afatinib as first-line treatment of patients with advanced EGFR-mutant NSCLC. Clinical Trial Registration: Clinicaltrials.gov NCT04640870.

Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited. We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS). Among 123 patients with pre-existing AID who received ICI, the majority had been diagnosed with non-small cell lung cancer (NSCLC, 68.3%) and melanoma (14.6%). Most patients had a rheumatologic (43.9%), or an endocrine disorder (21.1%). Overall, 74 (60.2%) patients experienced an immune-related adverse event (irAE) after ICI initiation, AID flare (25.2%), or new irAE (35%). Frequent irAEs included thyroiditis, dermatitis and colitis. ICI was permanently discontinued due to unacceptable (8.1%) or fatal (0.8%) toxicity. In patients with NSCLC, corticosteroid treatment at the initiation of immunotherapy was associated with poor PFS (HR = 2.78, 95% CI 1.40–5.50, p = 0.003). The occurrence of irAE was associated with increased PFS (HR = 0.48, 95% CI 0.25–0.92, p = 0.026). Both parameters maintained their independent prognostic significance. ICI in patients with cancer and pre-existing AID is associated with manageable toxicity that infrequently requires treatment discontinuation. However, since severe AID flare might occur, expected ICI efficacy and toxicity must be balanced. NCT04805099

Data on the effectiveness and safety of approved SARS-CoV-2 vaccines in cancer patients are limited. This observational, prospective cohort study investigated the humoral immune response to SARS-CoV-2 vaccination in 232 cancer patients from 12 HeCOG-affiliated oncology departments compared to 100 healthcare volunteers without known active cancer. The seropositivity rate was measured 2–4 weeks after two vaccine doses, by evaluating neutralising antibodies against the SARS-CoV-2 spike protein using a commercially available immunoassay. Seropositivity was defined as ≥33.8 Binding-Antibody-Units (BAU)/mL. A total of 189 patients and 99 controls were eligible for this analysis. Among patients, 171 (90.5%) were seropositive after two vaccine doses, compared to 98% of controls (p = 0.015). Most seronegative patients were males (66.7%), >70-years-old (55.5%), with comorbidities (61.1%), and on active treatment (88.9%). The median antibody titers among patients were significantly lower than those of the controls (523 vs. 2050 BAU/mL; p < 0.001). The rate of protective titers was 54.5% in patients vs. 97% in controls (p < 0.001). Seropositivity rates and IgG titers in controls did not differ for any studied factor. In cancer patients, higher antibody titers were observed in never-smokers (p = 0.006), women (p = 0.022), <50-year-olds (p = 0.004), PS 0 (p = 0.029), and in breast or ovarian vs. other cancers. Adverse events were comparable to registration trials. In this cohort study, although the seropositivity rate after two vaccine doses in cancer patients seemed satisfactory, their antibody titers were significantly lower than in controls. Monitoring of responses and further elucidation of the clinical factors that affect immunity could guide adaptations of vaccine strategies for vulnerable subgroups.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform cobas®EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

e21641 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the gold standard 1 st line strategy for non-small-cell lung cancer (NSCLC) patients with activating EGFR mutations (EGFRm), associated with improved survival outcomes and quality of life compared to chemotherapy. Despite the high response rate with first- and second- generation TKIs, most patients develop resistance to treatment and progress. The acquisition of T790M mutation in exon 20 is considered the most common resistance mechanism. This study aims to investigate the molecular epidemiology of EGFR resistance mutations, focusing on T790M in EGFRm NSCLC patients treated with TKIs. Methods: The study included patients with locally advanced/metastatic EGFRm NSCLC who have progressed on or after 1 st line treatment with first- or second- generation TKI. Samples either from plasma-based liquid biopsy and/or tissue re-biopsy were analysed using the Cobas EGFR Mutation Test v2. All patients signed informed consent and were enrolled between July 2017 and September 2019. Statistical analyses were performed using SAS software, Version 9.4. Results: Ninety-six eligible patients were enrolled. At the time of progression, T790M mutation was detected in 16.7%of the patients using plasma-based liquid biopsies. Among patients with negative T790M result, in plasma, tissue re-biopsy was performed in 22,7% with evaluable/valid results in 72.2% of them. T790M mutation was identified in 38.5% of re-biopsy samples. According to Cobas EGFR Mutation test results (combined plasma and tissue), T790M mutation was identified in 21.9% of the patients. Of T790M-positive patients 42.9% had previously received first and 57.1% second generation EGFR-TKI. Conclusions: Results from this study in real world clinical setting in Greece, show that EGFR-T790M acquired resistance positivity rate in plasma is lower compared to previous reports. Moreover, these data underline the challenges of implementing precision medicine using tissue re-biopsy in advanced/metastatic NSCLC. Clinical trial information: D133FR00126. [Table: see text]