TPS8665 Background: Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability. TTFields are delivered by a noninvasive portable device that has the European CE Mark and FDA approval for glioblastoma and mesothelioma. Preclinical non-small cell lung cancer (NSCLC) studies demonstrated that TTFields enhance the antitumor immune response, through disruption of mitosis and subsequent induction of immunogenic cell death. The pivotal, phase III LUNAR study (NCT02973789) in metastatic NSCLC progressing on/after platinum-based therapy demonstrated that TTFields with an immune checkpoint inhibitor (ICI) or docetaxel provided a statistically significant and clinically meaningful 3.3-month improvement in median overall survival (OS) vs an ICI or docetaxel alone, with no added systemic toxicities and no clinically significant difference on quality of life between groups. Despite advances in the treatment of NSCLC, survival rates for stage IV disease remain poor and there is a need for effective and tolerable treatments. Methods: LUNAR-2 (NCT06216301) is a pivotal, global, randomized, trial investigating the efficacy and safety of TTFields concomitant with pembrolizumab (P) and platinum-based chemotherapy (C) in patients (pts) with metastatic NSCLC, with a planned enrollment of 734 pts at 134 sites. Pts with NSCLC, radiologically evaluable disease in the thorax, ECOG PS of 0–1, and no prior treatment for metastatic disease are eligible. Pts will be stratified by histology, PD-L1 Tumor Proportion Score (TPS) and prior treatment with immunotherapy. Randomization is 1:1 to TTFields/P+C or P+C alone. Standard doses of P+C will be administered to both arms on day 1 of a 21-day cycle for 4 cycles of induction followed by up to 31 cycles of maintenance with TTFields/P or P alone. TTFields generated by the NovoTTF-200T System, will be delivered to the thorax ≥ 18 h/day until local disease progression per iRECIST. The primary endpoints are OS and progression-free survival (PFS) per RECIST v1.1 as assessed by a blinded independent central review (BICR). Secondary endpoints include OS and PFS according to histology or PD-L1 TPS, objective response rate, duration of response, and disease control rate, all per RECIST v1.1 as assessed by BICR and by investigator, comparing TTFields/P+C vs. P+C alone. Other secondary endpoints include PFS rates at 6, 12, 24 and 36 months per RECIST v1.1 as assessed by BICR, 1-, 2-, and 3-year survival rates and safety. Device Support Specialists will provide technical and lifestyle integration training for pts and caregivers throughout TTFields therapy. Pts usage is tracked by the device and is provided to pts and physicians to facilitate discussions to optimize outcomes by maximizing time on therapy. The trial is currently recruiting. Clinical trial information: NCT06216301 .

This paper presents a bibliometric analysis in the Mobile Commerce (MC) field to assess publication trends and thematic developments from 2000 to 2023. Using data from the Web of Science Core Collection and the SciMAT tool, the study identifies five stages in the evolution of MC, segmented according to technological advancements, and proposes a technology-driven periodization. Strategic diagrams and evolution maps are used to classify themes into motor, basic or transversal, specialised and peripheral, and emerging or declining categories.The results show a growing body of literature, reaching a peak in 2012 and maintaining sustained interest until 2022. Significant shifts in research themes are observed, moving from early technological aspects to user acceptance, satisfaction, consumer behaviour, trust, mobile marketing, and more recently, artificial intelligence and sustainability.The findings highlight that, despite ongoing challenges related to security and infrastructure, MC has a positive impact on economic growth and the continuous evolution of business practices. The study concludes by identifying future research directions, including customer journey analysis, value co-creation, and the integration of emerging technologies such as blockchain and augmented reality.

Understanding feature relationships in large-scale configurable software is critical for maintenance, refactoring, and testing. Kconfig, the configuration language used by the Linux Kernel, Coreboot, Buildroot, U-Boot, and many other systems, presents particular challenges due to its scale and semantic complexity. To clarify those relationships, graphs of transitive feature dependencies and conflicts that occur in all configurations are very helpful. The known approach to obtaining those graphs first translates Kconfig models into Boolean logic and then uses SAT solvers to obtain the transitive relationships. This approach has two fundamental limitations: (1) despite more than a decade of research, the translation from Kconfig to Boolean logic remains incomplete (i.e., no translation considers the whole Kconfig’s semantics), and (2) identifying the transitive relationships is computationally expensive, requiring numerous costly SAT solver calls. This paper presents a novel approach that sidesteps both challenges by combining pragmatic configuration sampling with association rule mining. To test the approach, we generated 1,000 configurations from Coreboot 4.13 firmware using the randconfig ^+ tool, and applied the Apriori algorithm to extract 79,464 dependencies and 1,206,384 conflicts.

Background:Geographic variability in epidermal growth factor receptor (EGFR) mutation rates in early-stage non-small cell lung cancer (NSCLC) has been reported. However, the frequency of EGFR mutations in patients with early-stage resected NSCLC in Spain has not been previously investigated. We aimed to determine the prevalence of EGFR mutations in patients with early-stage resected NSCLC in Spain. Methods:This was an observational, multicenter, cross-sectional study. Sensitizing EGFR mutations were assessed via real-time polymerase chain reaction (PCR)-based molecular analysis with the IdyllaTM EGFR Mutation Test, and next-generation sequencing (NGS) analysis with the OncomineTM Precision Assay. Results:A total of 172 patients with surgically resected non-squamous NSCLC were analysed. Median age was 67.5 years and 57.6% were male, 96.5% had adenocarcinoma histology and 65% had stage IA/IB. EGFR mutations were found using IdyllaTM EGFR Mutation Test in 25 patients out of 172 patients (14.5%), which consisted of exon 19 deletion in 13 patients (7.6%), exon 21 L858R point mutation in 11 (6.4%), and exon 20 mutation (T790M) in 1 (0.6%) patient. The OncomineTM test was conducted in 128 patients, which detected exon 19 deletions in 10 patients (7.8%), exon 21 mutations in 10 patients (7.8%), and exon 20 insertions in 5 (3.9%) patients. The OncomineTM test was able to detect concurrent mutations in tumor suppressor genes (TP53, PI3KCA, CDKN2A, PTEN) and another actionable alteration beyond EGFR, such as mutations in KRAS G12C (22%), ERBB2 (6%), METex14 (2%), BRAF V600E (2%) and ALK and ROS1 fusions (2%, each). Conclusions:The prevalence of EGFR mutations in early stage (IA-IIIB), resectable, non-squamous NSCLC observed in our study is consistent with that reported in advanced NSCLC in Spain. Molecular testing is crucial in early-stage NSCLC and can be performed either with single-gene testing or NGS.

Perioperative chemoimmunotherapy (ChIO) has become a paradigm shift in the treatment of patients with locally advanced non-small cell lung cancer (NSCLC), considerably increasing complete pathological response (CPR) and survival rates. The role played by B lymphocytes in the antitumor response emerges as a crucial factor in the fight against cancer, although mechanisms remain to be elucidated. Therefore, the main objective of this study is the identification of B lymphocyte-related mechanisms and biomarkers of response to perioperative chemoimmunotherapy treatment in patients with locally advanced NSCLC. For this purpose, tumor tissue B-cell receptor (BCR) repertoire, gene expression profile by bulk RNA sequencing, and qualitative localization by spatial transcriptomics have been characterized in 110 NSCLC patients receiving ChIO from NADIM and NADIM II trials (NCT03081689 and NCT03838159). Results of this work show an association between CPR and neoadjuvant treatment with a more diverse (p=0.069) and less even (p=0.030) BCR repertoire in pre-treatment tissue, which appears to be dominated by a set of more frequent clones (top 10, p=0.043). In addition, neoadjuvant chemoimmunotherapy induced overexpression of B lymphocyte-related genes in surgical tissue, mainly localized at tertiary lymphoid structures (TLSs) identified by spatial transcriptomics. Those tumors with low BCR repertoire evenness (CPR response) exhibited a different gene expression profile compared to highly even tumors (non-CPR). TLSs area and density were higher in CPR/low evenness sample compared to NCPR/high evenness; and functional T helper lymphocytes, defined as T CD4 lymphocytes colocalized with antigen presentation genes, were detected only in CPR/low evenness sample. In conclusion, tumor BCR repertoire clonality is associated to CPR after neoadjuvant ChIO. Neoadjuvant ChIO induces expression of B cell related genes in the context of TLS, being their area and functionality dependent on baseline BCR repertoire clonality. Belen Sierra-Rodero, Cristina Martínez-Toledo, Marta Molina-Alejandre, Ángeles Gil-González, Ernest Nadal, Alex Martinez-Marti, Bartomeu Massuti, Amelia Insa, Joaquín Casal, Javier de Castro, Rosario García Campelo, José Luis González-Larriba, Reyes Bernabé, Santiago Ponce, Manuel Dómine, Noemí Reguart, Carlos Camps, Guillermo López Vivanco, Manuel Cobo, Virginia Calvo, Ana Collazo-Lorduy, Mariano Provencio, Alberto Cruz-Bermúdez. B cells mediate antitumor immune response and predict pathological response in locally advanced NSCLC patients treated with perioperative chemoimmunotherapy (NADIM trials) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4542.

8527 Background: The addition of RELA HD, a lymphocyte activation gene-3 (LAG-3) inhibitor, to NIVO + PDCT has improved clinical benefits vs NIVO + PDCT for pts with PD-L1 expression ≥1% and NSQ histology in RELATIVITY-104 study. We report exploratory biomarker analyses from this study to elucidate mechanisms underlying NIVO + RELA HD + PDCT activity. Methods: Baseline and on-treatment blood samples were analyzed by flow cytometry for pharmacodynamic (PD) changes in immune cell populations including proliferating LAG-3-expressing CD4+ and CD8+ effector memory (EM) and central memory (CM) T cells. Baseline tumor samples were analyzed by monoplex immunohistochemistry (IHC) for tumor cell PD-L1, LAG-3, and CD8 expression. Associations between biomarkers and overall response rate (ORR) and progression free survival (PFS) were assessed. Results: NIVO + RELA HD + PDCT significantly modulated levels of proliferating LAG-3 expressing EM and CM T cells in the periphery on-treatment; no such PD change was observed with NIVO + PDCT. Among pts with NSQ histology, baseline tumor LAG-3 expression ≥1% showed improved ORR and median PFS in both treatment arms compared with LAG-3 <1%. Further, the benefit of RELA HD addition to NIVO + PDCT was also seen in patients with LAG-3 <1%, suggesting that baseline LAG-3 expression at 1%, unlike PD-L1 expression, would not help identify patients who can benefit from LAG-3 inhibition (Table). In contrast to NSQ, the same association trend of PD-L1 and LAG-3 expression with efficacy was not observed in pts with SQ histology, which could be partly attributable to the limited sample size in some SQ subgroups. Interestingly, PD-L1 ≥1% is more strongly correlated with CD8 T cells in NSQ as compared to SQ. Conclusions: These data represent the first in-depth biomarker analyses from a randomized phase 2 study to reveal that RELA can expand proliferating LAG-3 expressing T cells in NSCLC. NIVO + RELA HD + PDCT activity might be particularly robust in pts with NSQ histology and PD-L1 expression ≥1%, where CD8 T cells are enriched. The ongoing phase 3 RELATIVITY-1093 study is evaluating 1L NIVO + RELA HD + PDCT vs standard-of-care pembrolizumab + PDCT in mNSCLC. Clinical trial information: NCT04623775 . Efficacy of NIVO + RELA HD + PDCT vs NIVO + PDCT in pts with NSCLC by baseline histology, PD-L1 and LAG-3 expression. NIVO + RELA HD + PDCTvsNIVO + PDCT NSQ, PD-L1 ≥1%(n = 50 vs 48) NSQ, PD-L1 <1%(n = 48 vs 46) NSQ,LAG-3 ≥1%(n = 56 vs 42) NSQ,LAG-3 <1%(n = 38 vs 42) SQ,PD-L1 ≥1%(n = 29 vs 23) SQ,PD-L1 <1%(n = 22 vs 21) SQ,LAG-3 ≥1%(n = 38 vs 34) SQ,LAG-3 <1%(n = 13 vs 10) PFS HR(90% CI) 0.55(0.36–0.85) 1.24(0.84, 1.83) 0.81(0.54, 1.22) 0.79(0.51, 1.23) 0.78(0.46, 1.34) 1.25(0.7, 2.23) 0.97(0.61, 1.52) 0.98(0.45, 2.15) ORR, % 58% vs 39.6% 35.4% vs 34.8% 57.1% vs 45.2% 34.2% vs 26.2% 44.8% vs 43.5% 81.8% vs 66.7% 52.6% vs 55.9% 84.6% vs 50%

8604 Background: NSCLC patients with EGFR mutations develop resistance when treated with EGFR TKI. We previously reported that osimertinib combined with TPX-0005 (repotrectinib) ablated STAT3, paxillin, and YAP1 phosphorylation in a preclinical model. Osimertinib-induced Src and FAK phosphorylation was abrogated with TPX-0005 alone or in combination with osimertinib in H1975 (EGFR L858 and T790M) cell line. TPX-0005 potentiated the effect of osimertinib in PC9 and H1975 tumor xenografts without substantial toxicity (Karachaliou et al. eBioMedicine 2017). The findings prompted us to carry out the current study with osimertinib plus TPX-0005, which inhibit Src/FAK/JAK2, in addition to ALK, ROS1 and NTRKs. Methods: TOTEM (NCT04772235) is a phase I, two-part study to assess safety, tolerability, pharmacokinetics, and antitumor activity of repotrectinib plus osimertinib in EGFR-mutant patients resistant to previous lines of treatment. Phase Ia was a dose escalation (3+3). Treatment naïve patients were treated with osimertinib 80mg QD plus: repotrectinib 80mg QD, 160mg QD and 160mg BID. In part Ib, patients should have received osimertinib or osimertinib plus chemotherapy as first line treatment. Results from part Ia are presented in this abstract. Results: Phase Ia included 15 patients with a median age of 61 yrs (34-71). Of these patients:10 were female (66.7%), 9 had PS1 (60%), and 7 had brain metastasis (48.7%). At the time of starting treatment, two patients had exon 18 (G719X) mutations (p.E709_T710delinsD and p.G719A), 5 had exon 21 (4 p.L858R, 1 p.L861Q) and 8 had exon 19 deletion. Eight patients had p53 co-mutations, other co-alterations included PIK3CA, RET, FAT1, FGFR3 and MYC mutations, CDK4 and EGFR amplification, and MET, ROS1, EGFR and FGFR3 over-expression. Six patients were treatment-naive, four were osimertinib progressors, and five had received two or more previous lines of treatment. With repotrectinib plus osimertinib, intracranial complete response was attained in 3 of the seven patients with brain metastasis (42.85%). The overall objective response rate (ORR) was noted in 5 patients (33.3%), and stable disease in 8 patients (53.3%). Median PFS was 4.4 mo. (95% CI 2.9-NR). Among the adverse events, transient, manageable dizziness was observed in 76% of the patients, and dysgeusia occurred in 48% of cases. Most side effects were grade 1-2, including anemia, diarrhea, fatigue, and liver enzyme elevation. Pharmacokinetic analysis indicated a favorable profile of the combination. Dose level 3 (160mg BID) was safe, therefore, part Ib continued with repotrectinib 160mg BID plus osimertinib 80mg QD in 15 patients enrolled. Conclusions: In Part Ia osimertinib + repotrectinib showed impressive intracranial ORR with a manageable safety profile. Part Ib with repotrectinib 160 mg BID plus osimertinib 80 mg is ongoing. Updated results will be presented. Clinical trial information: NCT04772235 .

8013 Background: Small-cell lung cancer (SCLC) is an aggressive malignancy, accounting for 13% of all lung cancers, with a 5-year survival rate below 12%. Relapsed SCLC remains a major therapeutic challenge, underscoring the need for innovative second-line treatments. The combination of lurbinectedin (LUR) plus atezolizumab (ATZ) has shown synergy in immunocompetent models, and clinical feasibility in a phase I trial. Here we evaluate the efficacy and safety of the regimen as second line treatment for SCLC patients. Methods: This prospective, open-label, multicenter study enrolled patients with ECOG PS 0-1, measurable disease by RECIST 1.1, and progression after one prior platinum-based chemotherapy alone (cohort 1 - C1) or combined with PD-1/ PD-L1 blockade (cohort 2 - C2). Key inclusion criteria included a chemotherapy-free interval (CTFI) of ≥30 days, adequate organ function. Treated brain metastases previously managed with radiotherapy were permitted. Patients received LUR (3.2 mg/m² i.v. 1 hour infusion) following ATZ (1200 mg i.v. 30–60 minutes infusion) on day 1, every 3 weeks. Primary G-CSF prophylaxis was administered for 5 days. The primary endpoint was overall response rate (ORR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: Between June 2022 and March 2024, 218 patients were screened, and 151 were enrolled: 68 in C1 and 83 in C2. The median age was 64 years (range: 45–79), with 58% being male. Most patients (73%) had an ECOG 1, and 60.92% had a CTFI of ≥90 days. Efficacy results are summarized in Table 1. The combination was well-tolerated, with no unexpected safety signals. Treatment-emergent adverse events (TEAEs) were reported in 91% of patients. Grade ≥3 hematological toxicities included neutropenia (C1: 16.18%; C2: 7.23%), febrile neutropenia (C1: 2.94%; C2: 2.41%) and thrombocytopenia (C1: 8.82%; C2: 1.20%). Treatment- emergent deaths occurred in 7 patients (C1: 4; C2: 3). Conclusions: The combination of LUR and ATZ showed promising efficacy in patients with relapsed SCLC regardless of prior exposure to immunotherapy, including those with resistance to platinum. The associated safety profile is manageable. The regimen is being evaluated in a phase III trial in the maintenance setting (IMforte trial NCT05091567). Clinical trial information: NCT04253145 . Cohort 1 (n=68) Cohort 2 (n=83) CTFI<90 (n=59) CTFI≥90 (n=92) Overall Response,% (95% CI) 44.12 (32.27-56.63) 37.35 (27.18-48.7) 35.59 (23.87-49.20) 43.48 (33.30-54.20) CR, n (%) 3 (4.41%) 1 (1.20%) 0 (0.00%) 4 (4.35%) PR, n (%) 27 (39.71%) 30 (36.14%) 21 (35.59%) 36 (39.13%) SD, n (%) 21 (30.88%) 25 (30.12%) 20 (33.90%) 26 (28.26%) Median PFS (months), n (95%CI) 4.90 (3.87-7.27) 4.43 (3.27-5.17) 4.77 (3.27-5.90) 4.63 (3.60-6.13) Median OS (months), n (95%CI) 11 (9.37-15.07) 9.53 (7.90-12.87) 10.10 (8.17-11.97) 11 (8.67-15.07)

INTRODUCTION:We present the LEAP-006 (NCT03829319) phase 3 study evaluating the addition of lenvatinib to first-line pembrolizumab plus chemotherapy in metastatic nonsquamous NSCLC. METHODS:Adults with previously untreated stage IV nonsquamous NSCLC without targetable genetic alterations were randomized 1:1 to lenvatinib 8 mg/d or placebo once daily plus pembrolizumab 200 mg every 3 weeks with pemetrexed and carboplatin or cisplatin for 4 cycles, followed by pembrolizumab (≤35 total cycles) and pemetrexed until disease progression or intolerable toxicity. Primary end points were progression-free survival and overall survival (OS). Part 1 was an open-label safety run-in of lenvatinib plus pembrolizumab and chemotherapy; part 2 was the randomized, double-blind study. RESULTS:Participants (n = 748) were randomized to the lenvatinib (n = 375) or placebo (n = 373) arms. Median follow-up at final analysis (August 11, 2023) for OS was 36.8 months. Median (95% confidence interval [CI]) progression-free survival was 12.1 (10.4-14.1) versus 9.5 (8.3-10.7) months in the lenvatinib and placebo arms, respectively (hazard ratio, 0.88 [95% CI, 0.74-1.05]; 1-sided p = 0.07976). Median (95% CI) OS was 21.8 (18.6-24.0) versus 22.1 (19.7-24.2) months (hazard ratio, 1.05 [95% CI, 0.88-1.26]; 1-sided p = 0.70818). Grade 3 or higher treatment-related adverse events occurred in 69.7% and 55.6% of participants, respectively (grade 5, 5.6% versus 2.7%). CONCLUSIONS:Adding lenvatinib to first-line pembrolizumab plus chemotherapy did not improve efficacy versus pembrolizumab plus chemotherapy in stage IV nonsquamous NSCLC without targetable genetic alterations. There were no new safety signals. Pembrolizumab plus chemotherapy remains a standard of care for this population. TRIAL REGISTRATION:ClinicalTrials.gov (https://clinicaltrials.gov/), NCT03829319.

BACKGROUND:In Spain, next-generation sequencing (NGS) is currently available in a limited number of specialized centers and remains inaccessible to a significant proportion of patients. The ATLAS study aims to explore the tumor molecular profile beyond known EGFR mutations and ALK translocations using NGS on tumor biopsy samples. METHODS:Patients with EGFR-sensitizing mutations or ALK translocations were excluded. A total of 455 patients with advanced non-small cell lung cancer (NSCLC) were enrolled from 22 Spanish hospitals. DNA and RNA were extracted from formalin-fixed paraffin-embedded samples, and libraries were prepared using the Oncomine Focus Assay. The Trialing app was used to identify active clinical trials in Spain. RESULTS:Mutations were detected in 65.7 % of the cases. Local pathology assessments detected druggable mutations in only 7.9 % of cases, while centralized NGS testing increased this detection rate to 25.9 %. The most prevalent druggable alteration was KRAS G12C (53.6 %), followed by MET amplification (8.1 %) and MET exon 14 skipping (7.3 %). Additionally, 34.5 % of patients had molecular alterations matching clinical trials, offering potential treatment opportunities. Women had a significantly higher probability of harbouring druggable mutations (36 % vs. 20.3 %, p < 0.001), including the KRAS G12C which was significantly more frequent in females (22.6 % vs. 10 %). KRAS mutations were more common in adenocarcinomas and increased with tumor differentiation grade (p < 0.001 and p = 0.049, respectively). Likewise, ALK translocations, EGFR mutations, BRAF V600E, MET exon 14 skipping, and RET/ROS1 fusions were mainly found in adenocarcinomas whereas copy number variations were more frequent in squamous carcinomas (28.6 % vs. 15.1 %; p = 0.003) and in men (22 % vs. 11.6 %; p = 0.008). CONCLUSION:The ATLAS study demonstrates the utility of comprehensive NGS testing, which detects clinically relevant mutations in more than one-third of patients and may extend therapy options.

ABSTRACT:Preclinical studies have shown that interleukin (IL)-1β blockade can modulate the tumor microenvironment (TME) to activate antitumor immunity and, in combination with immune checkpoint inhibitors (ICIs), prevent cancer growth. Our study investigates if immune biomarkers in the TME affect outcomes in patients with non–small cell lung cancer (NSCLC) treated with the IL-1β inhibitor canakinumab plus an ICI-based therapy and describes canakinumab effects on the TMEs in these patients. Exploratory analyses were conducted in two prospective trials evaluating canakinumab combined with pembrolizumab-based regimens in patients with NSCLC: CANOPY-1 (first-line setting) and CANOPY-N (neoadjuvant setting). Immunohistochemistry (IHC) and transcriptomic analyses were performed on baseline tumor samples from CANOPY-1, and IHC and multiplex immunofluorescence analyses were performed on baseline and posttreatment tumor samples from CANOPY-N. Associations with clinical outcomes were evaluated. In CANOPY-1, in patients with low levels of T-cell infiltration in the tumor, the addition of canakinumab to a pembrolizumab-based regimen was associated with progression-free and overall survival improvements. Low levels of T-cell infiltration were associated with an immunosuppressive gene expression phenotype, supporting the role of low T-cell infiltration as a surrogate of an overall immunosuppressive TME. In CANOPY-N, a reduction in immunosuppressive cells in the TME was observed following canakinumab and pembrolizumab treatment. Our exploratory biomarker analyses from the CANOPY-1 and CANOPY-N trials suggest that IL-1β blockade may shift the TME toward an immune-activated status and that patients with immunosuppressive TME features could benefit from the addition of canakinumab to an ICI-based treatment. SIGNIFICANCE:Patients with NSCLC with immunosuppressive tumor features and low T-cell infiltration derive less benefit from ICI-based treatment. Biomarker analyses presented here suggest that these patients may benefit from the addition of anti-IL-1β therapy to their treatment.

In this study, we evaluate the effectiveness of foundational artificial intelligence (AI) models, particularly large language models (LLMs), in comparison to traditional machine learning methods for predicting tumor relapse in patients with non-small-cell lung cancer (NSCLC). With a high recurrence risk in NSCLC, early and accurate prediction is essential for improving patient outcomes and guiding treatment decisions. Our analysis utilizes a dataset of 1,348 patients, examining the performance of traditional machine learning models such as Random Forest, alongside cutting-edge LLMs like Mistral-7B, LLaMA-7B, Falcon-7B, and GPT-based models. While the Random Forest model slightly outperforms Mistral-7B in precision-recall for relapse prediction, the comparable results suggest that both approaches offer valuable insights for early relapse detection. This study underscores the potential of integrating classical machine learning with foundational AI models to enhance predictive accuracy in cancer prognosis, providing pathways for more personalized medical interventions.

8599 Background: EVOKE-01 (NCT05089734) assessed the efficacy and safety of SG vs docetaxel in pts with mNSCLC that progressed after platinum-based chemotherapy and anti–PD-(L)1 (IO) treatment. The study did not meet statistical significance for overall survival (OS) at final analysis. Here, we report updated survival and safety outcomes after longer follow-up, providing insight into the tolerability of SG over a prolonged period of administration. Methods: Pts were randomized 1:1 to receive SG (n = 299; 10 mg/kg IV, days 1 and 8) or docetaxel (n = 304; 75 mg/m 2 IV, day 1) in 21-day cycles until progression or unacceptable toxicity. OS was the primary endpoint, while safety was a key secondary endpoint. Results: As of Oct 21, 2024, median follow-up was 23.5 months. Median exposure with SG vs docetaxel was 3.5 vs 2.3 months; 33.4% vs 17.7% of pts, respectively, were exposed to study drug for ≥6 months. The longer follow-up preserved the numerical improvement in OS favoring SG in the intent-to-treat population (HR 0.89, 95% CI: 0.74–1.07; P = .1028) and in subgroups of interest, including nonresponders to prior IO, and across squamous and nonsquamous histologies ( Table ). Most common any-grade treatment-emergent adverse events (TEAEs) with SG vs docetaxel were fatigue (57.8% vs 56.6%), diarrhea (52.7% vs 33.7%), and alopecia (43.6% vs 30.2%). In line with the primary analysis, 68.6% vs 76.0% of pts receiving SG vs docetaxel experienced grade ≥3 TEAEs, mainly neutropenia (25.3% vs 36.8%), fatigue (12.5% vs 9.7%), and diarrhea (10.5% vs 3.8%). Discontinuations due to TRAEs were seen in 7.4% vs 14.2% of pts receiving SG vs docetaxel. There were no additional AEs leading to death reported with longer follow-up (Table). Conclusions: Consistent with the final analysis, SG showed a numerical improvement in OS vs docetaxel. Long-term safety showed SG is well tolerated, consistent with minimal increase in AE rates since prior report and an improved safety profile over docetaxel, despite longer treatment exposure. Clinical trial information: NCT05089734 . Median OS, mo (95% CI) HR (95% CI) SG Doc Nonresponsive (SD/PD) to last IO n = 19211.8 (9.6–12.8)0.83 (0.66–1.04) n = 1918.3 (6.9–10.2) Responsive (CR/PR) to last IO n = 1069.7 (8.4–14.3)1.05 (0.78–1.43) n = 11310.8 (9.2–12.8) Squamous n = 8410.3 (8.1–13.2)0.89 (0.63–1.25) n = 809.2 (6.9–11.0) Nonsquamous n = 21511.6 (9.4–12.9)0.89 (0.72–1.11) n = 2249.9 (7.9–11.2) With prior therapy for AGA n = 1912.9 (7.2–23.9)0.63 (0.31–1.29) n = 257.0 (5.2–11.6) TEAE, % (safety population)Any gradeGrade ≥3Serious TEAEsLeading to dose reductionLeading to discontinuationTRAEs leading to discontinuationLeading to deathTRAEs leading to death n = 296 99.768.647.629.710.17.43.41.4 n = 288 98.376.044.439.216.714.24.21.0

Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed the treatment of patients with non-small cell lung cancer (NSCLC). Numerous studies have suggested that immune-related adverse events (irAEs) are associated with ICI efficacy and can affect any organ system. This study aims to evaluate the prognostic significance of cutaneous IrAEs (cirAEs) and their impact on the effectiveness of PD-1/PD-L1 inhibitors in real-world NSCLC data. Methods: We retrospectively collected NSCLC patients treated with ICI as first- or second-line therapy between 2015 and 2022 at a single institution. We evaluated the association between cirAEs and treatment efficacy, measured by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Kaplan-Meier survival curves were generated, and log-rank tests were used for significance testing. Multivariable analysis was performed using Cox proportional hazards regression models. Results: A total of 510 patients were included in the analysis, with a median age of 62 years (range 34-85), and 75% of patients were males. CirAEs of any grade were observed in 139 patients (27.3%). Among patients assessed for efficacy, the ORR was significantly higher in those with cirAEs compared to those without (54.3% vs. 29.9%, p = 0.0001). At a median follow-up of 48 months, PFS (14.6 vs. 4.7 months, p = 0.0001) and OS (29 vs. 9.2 months, p = 0.0001) were significantly improved in patients with cirAEs. Patients with grade 1-2 cirAEs showed even greater survival benefits (PFS: median 14.9 months, p = 0.003; OS: median 30 months, p = 0.001). Multivariable analysis confirmed that the development of any cirAE was independently associated with significantly improved OS (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.44-0.80, p = 0.0001). The presence of multisystem ≥ 2 SOC irAEs, including cirAE, was strongly correlated with the greatest benefit from ICIs HR:0.51 (95% CI 0.35-0.74), p = 0.001. Conclusions: This study supports that cirAEs could be used as a potential marker of ICI efficacy in NSCLC. The development of multisystem cirAEs may prognose the greatest benefit of treatment.

Eftilagimod alpha (efti), an antigen-presenting cell (APC) activator, may overcome PD-1/PD-L1 inhibitor primary resistance. This phase II study investigated efti plus pembrolizumab treatment in patients with first-line metastatic non–small cell lung cancer (NSCLC) unselected for PD-L1. Patients, naïve to systemic therapy in the metastatic setting, received efti (30 mg subcutaneously every 2 weeks for eight 3-week cycles, then every 3 weeks up to 54 weeks) plus pembrolizumab (200 mg intravenously every 3 weeks for up to 105 weeks). The primary end point was objective response rate (ORR) by immune RECIST. Secondary end points included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and tolerability. Exploratory end points included identification and characterization of biomarkers. PD-L1 tumor proportion score (TPS) was assessed centrally. In the intention-to-treat population (n = 114), the median age was 67 years (range, 44-85), 73.7% was male, and 62.3% had an Eastern Cooperative Oncology Group performance status score of 1. Most patients (77.8%) had low/negative (<50%) PD-L1 TPS. The unconfirmed ORR (iRECIST) was 40.4%, leading to a confirmed ORR of 35.1%. The median DoR was 21.6 months, the DCR was 72.8%, and the median PFS (iRECIST) was 6.6 months. The median OS was 20.2 months, with 44.7% patients alive at 24 months. Antitumor activity was seen across all PD-L1 levels. A low proportion of patients had treatment-related adverse events leading to permanent discontinuation (8.8%). The APC activator, efti, on top of pembrolizumab was well tolerated and showed encouraging antitumor activity in patients with first-line NSCLC irrespective of tumor PD-L1 expression.

Objective: The aim of the NALOPOOL project was to assess the efficacy and safety of naloxegol in patients with cancer pain who exhibited opioid-induced constipation (OIC) and were treated under real-world conditions. Methods: We pooled individual patient data from three multicenter observational studies conducted with naloxegol in patients with cancer who exhibited OIC and were prescribed naloxegol under real-world conditions. Efficacy outcomes were evaluated after 4 weeks of treatment. All analyses were performed via a visit-wise approach. Heterogeneity was assessed via Cochran’s Q-test or Levene’s test. Results: Spontaneous bowel movements (SBM) response (≥3 SBM per week and an increase of ≥1 from baseline; three studies) was reported in 223 of 314 evaluable patients (71%, 95% CI 66–76); clinically relevant improvement in the Patient Assessment of Constipation Quality-of-Life Questionnaire (>0.5 points; three studies) occurred in 179 of 299 evaluable patients (60%, 95% CI 56–74) and in the Patient Assessment of Constipation Symptoms (>0.5 points; two studies) was reported in 131 of 190 evaluable patients (69%, 95% CI 62–76); and clinically relevant improvement in the Bowel Function Index (score ≥ 12 points at the endpoint; two studies;) was reported in 133 of 195 evaluable patients (68%, 95% CI 62–75). No significant heterogeneity was found for any efficacy outcome. The pooled proportion of patients who discontinued the drug owing to adverse reactions was 6.1% (95% CI 3.8% to 8.4%). Conclusions: Our results support the use of naloxegol for the management of OIC in patients with cancer pain who do not respond to laxative treatment.

El objetivo de este trabajo es analizar las investigaciones publicadas sobre la temática de género, a partir de las bases de datos bibliográficas internacionales Web of Science y Journal Citation Reports, durante el periodo comprendido entre el 1985 hasta el 2023, distribuido en cuatro etapas cronológicas. Para lograr este objetivo, recuperamos todos los trabajos publicados en las revistas internacionales indexadas en las categorías de género y Trabajo Social y las palabras clave más consensuadas en el tesauro. En la metodología, se emplea como herramienta para el análisis el software SciMat, para seleccionar la importancia de cada temática en virtud de su espacio bidimensional o diagrama estratégico. Así mismo, se determinan las medidas de rendimiento para evaluar en cada área temática los diagramas estratégicos en función del número de documentos publicados, citas e índice H. También analizamos mediante técnicas de mapas de ciencia el contenido de los trabajos científicos e identificamos los temas de investigación más relevantes y emergentes que pueden ser de interés para la producción científica. Según los datos, concluimos que la comunidad científica del Trabajo Social que investiga en materia de género, centra sus nudos de interés en las áreas de interseccionalidad, salud, orientación e identidad de género, violencia y familia, que han ido incrementando su producción científica en los últimos años en paralelo a los cambios sociales subyacentes en cuanto a género e igualdad. En orden opuesto, feminismo, y trabajo han ido perdiendo publicaciones en las últimas etapas, en sintonía con los nuevos focos de interés de las personas investigadoras.

OBJECTIVES:The determination of actionable genes is a necessity in lung cancer for proper care practice. The Spanish Lung Cancer Group (Fundación GECP) has performed an exploratory analysis of this aspect, specifically in stage IV non-small cell lung cancer (NSCLC). MATERIALS AND METHODS:The Thoracic Tumor Registry (TTR) is a Spanish prospective, observational cohort study. At the time of data extraction (March 2024), 27,399 patients were enrolled from 82 hospitals. RESULTS:There were 13,583 patients with stage IV NSCLC. The analysis of at least one tumor marker was performed in 85.7 % of non-squamous and 62.8 % of squamous patients (p-value < 0.001), with differences between autonomous communities. In the non-squamous population, the three most frequently analysed markers were EGFR (77.3 %), ALK (66.1 %) and PD-L1 (56.3 %). Biomarker profiling has undergone a more pronounced and extensive development in squamous histology in recent years. Molecular determinations that do not have a generally approved targeted therapy have also increased. Biomarker testing in patients with ECOG PS 2 is lower compared to ECOG PS < 2 (77.6 % vs 82.6 %, p-value < 0.001). Sub-analysis shows rates also vary by hospital size. CONCLUSION:The analysis of tumor markers in stage IV NSCLC patients continues to increase in Spain, at the same level as in Europe o USA, despite the absence of national plans. There are clinically guided determinations that are rare in squamous histology but have an appreciable percentage of positivity. Even in patients with ECOG PS2, biomarker testing with high clinical suspicion should be considered. CLINICAL TRIAL REGISTRATION:NCT02941458.