Extensive Stage Research Articles

P1.13A.03 MOZART: Phase II Trial of Monalizumab, Durvalumab, and Platinum-based Chemotherapy for First-Line Treatment of Extensive Stage SCLC

P1.13A.03 MOZART: Phase II Trial of Monalizumab, Durvalumab, and Platinum-based Chemotherapy for First-Line Treatment of Extensive Stage SCLC

Prise en charge des cancers bronchiques à petites cellules de stade localisé i actualisation

Limited-stage small cell lung cancer (LS-SCLC) represents 15-20 % of all lung cancers, and because of its rapid tumor kinetics, less than a third of SCLC are discovered at limited stage. The different steps and modalities of its management are well defined and codified. They involve a comprehensive staging assessment using CT scans of the chest, abdomen, and pelvis, PET-CT scans, and ideally brain imaging using MRI to avoid missing a more extensive stage of the disease, which would significantly alter the treatment strategy. The treatment consists of a combination of chemotherapy with platinum/ etoposide and radiotherapy, possibly delivered in a hyperfractionated schedule with two daily sessions. SCLC is particularly both chemosensitive and radiosensitive, so that the initial evaluation shows frequently a complete response, and prophylactic cranial irradiation (PCI) is then recommended. Relapses are unfortunately frequent, less responsive to second line treatments, and therapeutic options are limited. No targeted agents or immunotherapy have robustly demonstrated efficacy in the treatment of LSSCLC. Even if hyperfractionated accelerated radiotherapy (HFART) at the dose of 45Gy in 30 fractions has given the best results, most clinicians use once-daily chemoradiation regimen (60-70Gy). Studies have evaluated dose escalation either with HFRAT or with conventional fractionation (66 to 70Gy). Several trials are currently investigating the addition of immunotherapy to chemoradiation, hippocampus sparing PCI or the omission of PCI. In rare cases of very early-stage SCLC, surgery or stereotactic radiotherapy may be envisaged.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

EP.13D.04 The Conflicting Impacts of G-CSF on the Therapeutic Efficacy of Chemoimmunotherapy for Extensive Stage Small Cell Lung Cancer

EP.13D.04 The Conflicting Impacts of G-CSF on the Therapeutic Efficacy of Chemoimmunotherapy for Extensive Stage Small Cell Lung Cancer

EP.13B.09 Outcomes of Inpatient Chemotherapy for Patients with Newly Diagnosed Extensive Stage Small Cell Lung Cancer

EP.13B.09 Outcomes of Inpatient Chemotherapy for Patients with Newly Diagnosed Extensive Stage Small Cell Lung Cancer

Study on the extension mechanism of fissures in expansive soil based on fracture mechanics test method

Expansive soil, characterized by widespread fissures, is a special type of soil prone to localized fissure propagation, leading to failure and instability, often resulting in landslides. Numerous studies have applied fracture mechanics theory to analyze soil failure along fissures, but no standardized testing method has been established. This paper reviews existing soil fracture toughness testing methods, designs an integrated system combining digital image correlation(DIC) technique and electrical resistance testing, and employs the Cracked Chevron-Notched Brazilian Disc (CCNBD) method to assess the fracture toughness of expansive soil. The deformation and internal damage accumulation processes of the specimens were monitored. The KΙc and KΙΙc of expansive soil were tested at moisture contents of 15 %, 20 %, and 25 % using specimens with three different crack length ratios (a/R). The role of water was explored by injecting water into the fissures. The results showed that KΙc of expansive soil ranged from 10 to 36 kPa·m0.5, with a linear negative correlation to moisture content and a proportional relationship to tensile strength, having a proportionality coefficient of 0.331. The KΙΙc ranged from 20 to 70 kPa·m0.5,and it is greater than KΙc under the same conditions. Based on the load, internal damage, strain, and fissure area during the tests, the failure process of expansive soil along fissures was divided into four stages: initial deformation stage(I), quasi-elastic deformation stage(II), fissure extension stage(III), and failure stage(IV). Water injection into the fissures reduced the soil's fracture toughness, with a more significant reduction as a/R increased and the failure showed progressive behavior. The CCNBD method, combined with DIC technique and electrical resistance testing, effectively measures the fracture toughness of soil, aiding in understanding the failure mechanism along fissures and providing a basis for preventing and controlling landslides and other hazards in expansive soils.

Risk stratification and overall survival prediction in extensive stage small cell lung cancer after chemotherapy with immunotherapy based on CT radiomics

The prognosis of extensive-stage small cell lung cancer is usually poor. In this study, a combined model based on pre-treatment CT radiomics and clinical features was constructed to predict the OS of extensive-stage small cell lung cancer after chemotherapy with immunotherapy.Clinical data of 111 patients with extensive stage small-cell lung cancer who received first-line immunotherapy combined with chemotherapy in our hospital from December 2019 to December 2021 were retrospectively collected. Finally, 93 patients were selected for inclusion in the study, and CT images were obtained through PACS system before treatment. All patients were randomly divided into a training set (n = 66) and a validation set (n = 27). Images were imported into ITK-SNAP to outline areas of interest, and Python software was used to extract radiomics features. A total of 1781 radiomics features were extracted from each patient’s images. The feature dimensions were reduced by MRMR and LASSO methods, and the radiomics features with the greatest predictive value were screened. The weight coefficient of radiomics features was calculated, and the linear combination of the feature parameters and the weight coefficient was used to calculate Radscore. Univariate cox regression analysis was used to screen out the factors significantly associated with prognosis from the radiomics and clinical features, and multivariate cox regression analysis was performed to establish the prognosis prediction model of extensive stage small cell lung cancer. The degree of metastases was selected as a significant clinical prognostic factor by univariate cox regression analysis. Seven radiomics features with significance were selected by LASSO-COX regression analysis, and the Radscore was calculated according to the coefficient of the radiomics features. An alignment diagram survival prediction model was constructed by combining Radscore with the number of metastatic lesions. The study population was stratified into those who survived less than 11 months, and those with a greater than 11 month survival. The C-index was 0.722 (se = 0.044) and 0.68(se = 0.074) in the training and the validation sets, respectively. The Log_rank test results of the combination model were as follows: training set: p < 0.0001, validation set: p = 0.00042. In this study, a combined model based on radiomics and clinical features could predict OS in patients with extensive stage small cell lung cancer after chemotherapy with immunotherapy, which could help guide clinical treatment strategies.

Recent treatment patterns and real-world survival following first-line anti-PD-L1 treatment for extensive-stage small cell lung cancer.

The landscape of small cell lung cancer (SCLC) has changed since the 2019 and 2020 approvals of anti-PD-L1 atezolizumab and durvalumab for first-line (1L) treatment in combination with chemotherapy. We studied treatment patterns and real-world overall survival (rwOS) following 1L-3L therapy. A nationwide electronic health record (EHR)-derived de-identified database was used to describe treatment patterns, characteristics, and survival of patients with extensive-stage (ES)-SCLC by 1L anti-PD-L1 treatment. Patients with ES-SCLC who initiated ≥1 line of systemic therapy from 2013 to 2021, with potential follow-up through 2022, were included. Among 9952 patients with SCLC, there were 4308 patients with ES-SCLC treated during the study period who met eligibility criteria. Etoposide + platinum (EP) chemotherapy was most common in the 1L, with addition of anti-PD-L1 therapy to most regimens by 2019. Second-line regimens varied by platinum sensitivity status and shifted from topotecan to lurbinectedin over time. Median rwOS following 1L therapy was 8.3 months (95% CI, 7.9-8.8) in those treated with 1L anti-PD-L1 and 8.0 months (95% CI, 7.8-8.2) in those who were not. Following 2L and 3L, median rwOS was 5.6 (95% CI, 4.9-6.3) and 4.9 months (95% CI, 3.4-6.0), respectively, among 1L anti-PD-L1-treated, and 4.5 (95% CI, 4.2-4.9) and 4.0 months (95% CI, 3.7-4.5), respectively, among those who were not. Despite the introduction of frontline anti-PD-L1 therapy, survival remains dismal among patients with ES-SCLC treated in the real-world setting.

A simulated trial with reinforcement learning for the efficacy of Irinotecan and Ifosfamide versus Topotecan in relapsed, extensive stage small cell lung cancer

ObjectivesSynthetic data may proxy clinical data. At the absence of direct clinical data, this study aimed to compare Irinotecan and Ifosfamide (II) with Topotecan in synthetic, recurrent small cell lung cancer (SCLC) patients within a simulated clinical trial.Materials and methodsTwo simulation stages were conducted. Initially, 200 recurrent SCLC cases were simulated to replicate a previous phase 3 trial, testing the utility of Cox proportional hazards model and simulation methodology together, where patients were randomized to receive Cyclophosphamide, Adriamycin, Vincristine (CAV) or Topotecan. In the second stage, 600 recurrent SCLC patients were simulated and randomized to compare Topotecan versus II in terms of overall survival (OAS), using Reinforcement Learning (RL) and Cox proportional hazards model.ResultsCAV versus Topotecan comparison showed no statistical difference in overall survival (hazard ratio (HR): 0.89, 95% CI: 0.67–1.18, P = 0.418), aligning with the original clinical trial. For the Topotecan versus II comparison, the RL framework significantly favored the II arm (mean reward points: 193.43 versus − 251.82, permutation P < 0.0001). Likewise, II arm exhibited superior median OAS compared to Topotecan arm (11.12 versus 6.30 months). HR was 0.44 (95% CI: 0.38–0.52) with P < 0.0001, in favor of II.ConclusionArtificial trial results for CAV versus Topotecan matched the original trial, confirming indifference of OAS. Additionally, II yielded superior overall survival compared to Topotecan in recurrent SCLC patients. These demonstrate the potential of RL and simulation in conjunction with Cox modelling for similar studies. However, definitive conclusions necessitate a randomized clinical trial between II and Topotecan in this patient cohort.

Survey of Fungal Diseases on Barley, Wheat, and Oats at Tillering to Stem Extension Stages in Southern Regions of Korea during 2020-2021

Cereal, including barley, wheat, and oats, is a major winter food crop in Korea. Despite recent changes in agricultural environments in response to climate change, fungal diseases that could affect cereal productivity remain poorly understood. In this study, we investigated the incidence of diseases in barley, wheat, and oats in the southern part of Korea. We collected fungal pathogens from seven locations where cereals were grown. In March-April of 2020 and 2021, a total of 92 fungal isolates were collected, mainly from the stem base or leaves of cereal crops during the tillering and stem extension stages of cereals in Korea. The collected isolates were identified based on morphological and molecular biological characteristics. The dominant species was &lt;i&gt;Ceratobasidium cereale&lt;/i&gt; (42.4%), followed by &lt;i&gt;Pyrenophora teres&lt;/i&gt; (21.7%), &lt;i&gt;P. avenae&lt;/i&gt; (10.9%), &lt;i&gt;Alternaria alternata&lt;/i&gt; (6.5%), and &lt;i&gt;Epicoccum tobaicum&lt;/i&gt; (6.5%). In addition, &lt;i&gt;P. tritici-repentis&lt;/i&gt; (3.3%), &lt;i&gt;Cladosporium&lt;/i&gt; sp. (3.3%), &lt;i&gt;Fusarium&lt;/i&gt; sp. (3.3%), and &lt;i&gt;Nigrospora&lt;/i&gt; sp. (2.2%) were also collected as minority groups. Our results will provide information on fungal pathogens that occur during the growing season of cereals in Korea, particularly during the tillering and stem extension stages. In addition, the isolates collected from this study can serve as a valuable resource for conducting simulations on climate change, focusing on temperature and humidity.

Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial

ObjectivesCertain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP). MethodsIn this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase), followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate. ResultsTwenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3–99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6–6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached). ConclusionsChemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.

Insights into the crustal and the magmatic feeding structure at the Payunia Volcanic Province highlighted by geophysical methods, in the retroarc of the Southern Central Andes

The Payunia Volcanic Province is a Quaternary volcanic plateau emplaced in the retroarc area in the northern Neuquén Mesozoic Basin, associated with a hydrocarbon system. At deeper levels, this basin is linked to different intrusive systems that developed in the retroarc region at different times, during the Jurassic, Cretaceous, Eocene, Miocene, and even the Quaternary which influenced the hydrocarbon system maturity. We analyzed the Moho structure through this retroarc region, as well as the crustal structure affected by different stages of regional extension. From continuous seismic noise data, we calculated the autocorrelograms to obtain the reflection response below each seismological station. This allowed imaging the surface of primary crustal reflectors and in a few stations the top of an asthenospheric anomaly (SWAP) found by magnetotelluric survey and in concordance with satellite magnetic data. The crustal reflectors were identified in all stations at a mean two-way travel time of about ∼8.5 s and ∼12.5 s using frequency bands of about 1.0–2.4 Hz. Therefore, this is the first geophysical research that estimates the depth of the magmatic system, hosted at the top of the lower crust and the Moho discontinuity. The deepest reflector, only recognized in 4 stations, was observed with a two-way travel time of 17.2 s to 19.6 s. We used a mean one-dimensional Vp model to obtain the corresponding reflector depths which constrain the two-dimensional forward gravity model that fits with the observed regional anomaly for the region. We finally established a relationship between the shallowest sublithospheric electrical conductivity anomalies determined in previous researches and the strong deep reflections observed in some of the seismological stations. This information may help to constrain geochemical and petrological models and re-evaluate the hydrocarbon system maturity of the northern Neuquén basin.

Utilization of Indonesian E-Modules Based on The ICARE Approach as An Innovation in Learning for Students

This research aims to design and implement an Indonesian e-module based on the ICARE approach, which includes the stages of Introduction, Connection, Application, Reflection, and Extension. The method in this study was research and development (R&amp;D) with the ADDIE model. The stages conducted in this study were (1) needs analysis, (2) design, (3) product development, (4) implementation or trial, and (5) evaluation. The validity of the product was assessed by three experts in the fields of material, language, and media. The calculation of the data in this study was analyzed using a questionnaire with a Likert scale method. The response trial was conducted with junior high school students in grade VIII from 3 schools in Batam City. Based on the test results, it was obtained a score of 4.58 with a validity level of 89%. It provides evidence that the implementation of e-modules based on the ICARE approach in an educational environment can increase the effectiveness of Indonesian learning. Students can learn independently and collaboratively, and develop critical skills such as problem-solving, analysis, and synthesis of information.

Mechanism of oxygen content on impact toughness of α + β powder metallurgy titanium alloy

Understanding the mechanism of oxygen on toughness of titanium alloys is crucial for popularizing powder metallurgy. In this work, the effect of oxygen content (1500, 3000 and 5000 ppm) on the impact toughness of powder metallurgically modified titanium alloys with fine equiaxed microstructures (∼1.5 μm) was systematically investigated. With increasing oxygen content, the c/a value of the α-phase lattice parameter increases to a maximum of 1.593 Å, and the hardness increases from 4.03 GPa to 5.05 GPa, resulting in an increase in strength of ∼150 MPa and a considerable decrease in the ability of the two phases to coordinate. The crack initiation energy is similar for different oxygen contents, whereas the crack propagation energy increases considerably with decreasing oxygen content; the impact energy of stable crack extension increases from 4 J to 13 J and 35 J, and the impact energy of unstable crack extension and crack collapse stages increases from zero to 14 J and 25 J, respectively, indicating that decreasing oxygen content can substantially improve the crack extension resistance. The activation of numerous dislocations within the two phases and the formation of subgranular boundaries at low oxygen contents promote the release of internal stresses in the grains, and simultaneously, the interfacial resistance to dislocation migration and the concentration of interfacial stresses are also reduced, which improves the coordination of the two-phase plastic deformation of the equiaxed microstructures; the crack extension paths in the impact process become more tortuous and finally achieve impact energies as high as 85–100 J.

Prognostic Significance of the Advanced Lung Cancer Inflammation Index in Metastatic Small Cell Lung Cancer: A Retrospective Analysis of 96 Patients.

BACKGROUND The advanced lung cancer inflammation index (ALI) is regarded as a potential indicator of systemic inflammation. This retrospective study aimed to evaluate the prognostic role of the ALI in 96 patients with advanced small cell lung cancer (SCLC). MATERIAL AND METHODS This retrospective study included 96 patients who were diagnosed with extensive stage SCLC in a single institution between 2016 and 2022. The formula for ALI is body mass index (kg/m²)×serum albumin (g/dL)/neutrophil to lymphocyte ratio. Patients were divided into low inflammation (ALI ≥32.5) and high inflammation (ALI <32.5) groups. Kaplan-Meier analysis and Cox proportional analysis were conducted to assess the association between the ALI and patient prognosis. RESULTS Median age was 61 (range: 41-82) years. Median follow-up was 9 months, and median overall survival (OS) was 10 months (95% CI: 7.75-12.45). A lower ALI score (ALI <32.5) was correlated with a poorer OS than was a higher ALI score (median OS 7 months for ALI <32.5 95% CI: 4.6-9.3 vs 15 months for ALI ≥32.5, 95% CI: 10.6-19.3, P<0.001). In the multivariate analysis, ALI score, Eastern Cooperative Oncology Group performance status, brain metastasis, and bone metastasis were identified as independent prognostic factors. CONCLUSIONS ALI score is a substantial predictor of survival in SCLC as in other types of cancer types. Patients with a low ALI score have poorer survival. Assessment of ALI can identify lung cancer patients at high risk of poor prognosis and can be a useful prognostic marker in clinical practice.

Integration of clinical and blood parameters in risk prognostication for patients receiving immunochemotherapy for extensive stage small cell lung cancer: real-world data from two centers

BackgroundImmune checkpoint inhibitors (ICIs) had modest advances in the treatment of extensive-stage small cell lung cancer (ES-SCLC) in clinical trials, but there is a lack of biomarkers for prognosis in clinical practice.MethodsWe retrospectively collected data from ES-SCLC patients who received ICIs combined chemotherapy from two centers in China, integrated clinical and blood parameters, and constructed risk prognostication for immunochemotherapy. The population was divided into high- and low-risk groups, and the performance of the model was assessed separately in the training and validation cohorts.ResultsTwo hundred and twenty and 43 patients were included in the training and validation groups, respectively. The important predictors were screened including body mass index, liver metastases, coefficient variation of red blood cell distribution width, lactate dehydrogenase, albumin, and C-reactive protein. Predicting 1-year overall survival (OS), the AUC values under ROC for the model under training, internal validation, and external validation were 0.760, 0.732, and 0.722, respectively, and the calibration curve and clinical decision curve performed well. Applied the model to divide patients into low-risk and high-risk groups, and the median OS was 23.7 months and 9.1 months, and the median progression-free survival was 8.2 months and 4.8 months, respectively; furthermore, this ability to discriminate survival was also observed in the validation cohort.ConclusionsWe constructed a novel prognostic model for ES-SCLC to predict survival employing baseline tumor burden, nutritional and inflammatory parameters, it is easily measured to screen high-risk patient populations.

Fracture Behavior of Crack-Damaged Concrete Beams Reinforced with Ultra-High-Performance Concrete Layers

Reinforcing crack-damaged concrete structures with ultra-high-performance concrete (UHPC) proves to be more time-, labor-, and cost-efficient than demolishing and rebuilding under the dual-carbon strategy. In this study, the extended finite element method (XFEM) in ABAQUS was first employed to develop a numerical model of UHPC-reinforced single-notched concrete (U+SNC) beams, analyze their crack extension behavior, and obtain the parameters necessary for calculating fracture toughness. Subsequently, the fracture toughness and instability toughness of U+SNC were calculated using the improved double K fracture criterion. The effects of varying crack height ratios (a/h) of SNC, layer thicknesses (d) of UHPC reinforcement, and fiber contents in UHPC (VSF) on the fracture properties of U+SNC beams were comprehensively investigated. The results indicate that (1) the UHPC reinforcement layer significantly enhances the load-carrying capacity and crack resistance of the U+SNC beams. Crack extension in the reinforced beams occurs more slowly than in the unreinforced beams; |(2) the fracture performance of the U+BNC beams increases exponentially with d. Considering both the reinforcement effect benefit and beam deadweight, the optimal cost-effective performance is achieved when d is 20 mm; (3) with constant d, increasing a/h favors the reinforcement effect of UHPC on the beams; (4) as VSF increases, the crack extension stage in the U+BNC beam becomes more gradual, with higher toughness and flexural properties; therefore, the best mechanical properties are achieved at a VSF of 3%.

Evolution of rift faulting in incipient, magma-poor divergent plate boundaries: New insights from the Okavango-Makgadikgadi Rift Zone, Botswana

Continental rifts are thought to transition from a power-law fault length distribution during the juvenile stages of extension, to an exponential distribution during break-up and oceanic spreading. However, fault scaling relationships have rarely been quantified in natural incipient rifts, particularly in the absence of magmatic influence. We address this knowledge-gap in the incipient Okavango-Makgadikgadi Rift Zone, Northern Botswana, consisting of the amagmatic Okavango Rift Basin (ORB) and Makgadikgadi Rift Basin (MRB). We utilize high-resolution satellite topography data (12.5 m TanDEM-X and 30 m SRTM) and aeromagnetic data to image and map faults across the rift zones and generate a new robust fault map for the region. Further, we analyze the length-frequency distribution of faults using a two-sample Kolmogorov-Smirnov test. The results show that the Makgadikgadi Rift Basin exhibits an exponential distribution associated with a nucleating rift as it exhibits diffuse faulting and lacks a border-fault, whereas the Okavango Rift Basin exhibits a power-law distribution that is consistent with its relatively more evolved rift structure with established border faults. Thus, we propose that continental divergent plate boundaries commonly nucleate with an initial exponential distribution of fault lengths which subsequently transition into a power-law distribution as the rift evolves into its stretching phase, and may again transition into an exponential distribution as break-up initializes.

1812TiP IDeate-Lung03: A Phase Ib/II study of ifinatamab deruxtecan (I-DXd) plus atezolizumab (atezo) with or without carboplatin (carbo) as first-line (1L) induction or maintenance in patients (pts) with extensive stage (ES) small cell lung cancer (SCLC)

1812TiP IDeate-Lung03: A Phase Ib/II study of ifinatamab deruxtecan (I-DXd) plus atezolizumab (atezo) with or without carboplatin (carbo) as first-line (1L) induction or maintenance in patients (pts) with extensive stage (ES) small cell lung cancer (SCLC)

A Phase I Open-Label Study of Cediranib Plus Etoposide and Cisplatin as First-Line Therapy for Patients With Extensive-Stage Small-Cell Lung Cancer or Metastatic Neuroendocrine Non–Small-Cell Lung Cancer

IntroductionSmall cell lung cancer (SCLC) is known to express high levels of the proangiogenic factor vascular endothelial growth factor (VEGF). We assessed the safety and tolerability of cediranib, an oral inhibitor of VEGF receptor tyrosine kinases, in combination with etoposide and cisplatin as first-line therapy for extensive-stage (ES) SCLC or metastatic lung neuroendocrine cancer (NEC). MethodsPatients received up to six 21-day cycles of etoposide (100 mg/m2, days 1-3) and cisplatin (80 mg/m2, day 1) with once-daily cediranib until disease progression or unacceptable toxicity. Cediranib dosing started at 30 mg with de-escalation cohorts planned based on cycle 1 dose-limiting toxicities (DLTs). An expansion cohort of 12 patients was enrolled at the recommended phase II dose. ResultsTwenty-two patients (18 with ES SCLC, 4 with NEC) received treatment. Only 4 patients were enrolled at the 30 mg cediranib dose before other studies established 20 mg/day as the recommended dose with chemotherapy. Among the 18 patients enrolled at the 20-mg dose, common adverse events included nausea/vomiting, neutropenia, and diarrhea; 8 patients (44%) had grade 1 or 2 hypertension, and 2 (11%) had grade 3 hemoptysis. For all 18 patients, the objective response rate and median progression-free survival duration were 67% and 7.9 months. Plasma levels of VEGF were significantly higher, and those of soluble VEGFR2 were significantly lower, on day 22 than at baseline but were not correlated with tumor shrinkage. ConclusionsCediranib (20 mg) plus etoposide and cisplatin is well tolerated and has promising clinical activity.

1787P Intracranial response in patients (pts) with baseline (BL) brain metastases (BM) and extensive-stage (ES) small cell lung cancer (SCLC) treated with ifinatamab deruxtecan (I-DXd) in the IDeate-Lung01 study

1787P Intracranial response in patients (pts) with baseline (BL) brain metastases (BM) and extensive-stage (ES) small cell lung cancer (SCLC) treated with ifinatamab deruxtecan (I-DXd) in the IDeate-Lung01 study