Advanced Small Cell Lung Cancer Research Articles

Efficacy of first-line chemotherapy based on primary site of tumor versus etoposide-platinum in advanced gastroenteropancreatic neuroendocrine carcinoma.

Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) constitute a rare and aggressive group of malignancies usually with widespread disease. There are limited studies on GEP-NECs, and therefore, we aim to acquire more information on the clinical features, treatment regimens, and prognosis. Data from advanced GEP-NECs patients who had not previously received systemic treatment for advanced disease at The First Affiliated Hospital of Nanjing Medical University from 2010 to 2022 were retrospectively collected. Relationships between clinical-pathological features, treatment regimens, and prognosis were investigated using Kaplan-Meier curves and cox regression models. A total of fifty-four patients were enrolled in the study. The median age was 65.5 years and 79.6% were male. At diagnosis, 51.9% and 3.7% of patients developed liver and brain metastasis respectively. Sixteen (29.6%) patients received chemotherapy according to primary site of tumor (PST), while thirty-eight (70.4%) were treated with etoposide-platinum (EP) regimen, which based on the first-line treatment of advanced small cell lung cancer (SCLC). No significant differences on progression-free survival (PFS) and response rate were observed between these two groups. Univariate survival analysis showed that liver metastasis, elevated baseline serum carcinoembryonic antigen, elevated baseline serum neuron-specific enolase, elevated baseline serum lactate dehydrogenase, and elevated baseline serum neutrophil-to-lymphocyte ratio (NLR) were associated with shorter PFS. After multivariate analysis, elevated NLR was the only factor that remained significantly associated with shorter PFS (P=0.01). GEP-NECs are aggressive neoplasms, of which elevated NLR is proven to be an independent negative predictor. Treatment regimens based on PST are not inferior to regiments based on SCLC (EP) for GEP-NECs patients. Large-scale, prospective randomized controlled trials are required to establish the standard of care.

Natural history of SCLC patients treated in third-line and beyond: A retrospective real world study

ObjectivesTo describe treatment patterns and estimate outcomes among real-world small cell lung cancer (SCLC) patients in the US who received three or more lines of therapy. Materials and methodsWe conducted a retrospective analysis of adult patients with SCLC who received a front-line platinum-based regimen and two additional lines of therapy (ie., a cohort of at least three lines of therapy). De-identified patients were selected from a United States Flatiron Health oncology database of electronic health records. Treatment patterns were captured by line of therapy. Outcomes evaluated by line of therapy included real-world overall survival (rwOS), real-world progression free survival (rwPFS), real-world response rate (rwRR) and real-world duration of response (rwDOR). ResultsThe analysis included 326 3L SCLC patients, of which 103 (32 %) received 4L treatment, and 38 % (39/103) of 4L treated received 5L of therapy. Among the 3L cohort, the average age was 67 years, 49 % were male, and nearly all had a history of smoking (96 %). In the 3L setting, the median rwOS was 5.3 months (95 % Confidence Interval (CI): 4.5, 6.0), median rwPFS was 2.5 months (95 % CI: 2.1, 2.7), rwRR was 19.3 % (95 % CI: 15.2, 24.0) and median DOR was 3.4 months (95 % CI: 2.8, 4.4). No differences were seen in outcomes between the overall cohort and a subgroup of patients treated with front-line platinum-based regimen with an anti-programmed cell death ligand 1 (PD-L1) agent (atezolizumab or durvalumab), in each respective line of therapy. ConclusionResults from this large, real-world study of US patients with SCLC in the 3L setting and beyond highlight the poor treatment outcomes in advanced SCLC patients with existing therapies and underscore the dire need for new therapies for SCLC patients.

Abstract 7164: Exposure-efficacy and exposure-safety relationships of tarlatamab to inform dose selection and benefit-risk assessment in patients with advanced small cell lung cancer (SCLC)

Abstract Introduction: Tarlatamab is a first in class, half-life extended bispecific T-cell engager (BiTE) immunotherapy targeting delta-like ligand 3 (DLL3) that has shown promising anti-tumor activity and survival outcomes with manageable safety profile in clinical studies of patients with previously treated SCLC (NCT03319940, NCT05060016) (Ahn et al, 2023; Paz-Ares et al, 2023). Here we characterized the exposure-efficacy and exposure-safety profiles associated with tarlatamab treatment in SCLC, including the effects of patient-specific covariates (brain or liver metastasis, smoking status, number of prior lines of therapy, prior PD-1/PD-L1 inhibitor therapy, sum of target lesion diameters, and presence of anti-drug antibody). Methods: The analysis dataset consisted of 412 subjects with SCLC from ongoing Phase 1 DeLLphi-300 study (dose range 0.003 mg to 100 mg Q2W and 200 mg Q3W) and Phase 2 DeLLphi-301 study (10 mg and 100 mg Q2W). Serum tarlatamab exposure averaged over the first cycle (28 days) was utilized as the predictor of response in the regression analysis. Efficacy endpoints included objective response rate, disease control rate, best tumor size response, progression-free survival and overall survival (OS). Safety endpoints included overall treatment related adverse event (TRAE), overall treatment emergent adverse event (TEAE), and TEAEs of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurologic events, and neutropenia. Only the grade ≥ 3 adverse events (AEs) were evaluated. Results: Significant exposure-response relationships were established for all key efficacy measures across the dose range investigated. Plateau in the exposure-efficacy relationship (maximal efficacy) was observed at the recommended dose of 10 mg Q2W. Exposures associated with lower doses were estimated to have lower efficacy. No clear trends for exposure-response relationships were identified for the evaluated AEs except for grade ≥ 3 neutropenia, where a shallow trend was observed for increased neutropenia rate with increasing tarlatamab exposures. Of all the evaluated covariate relationships, only higher baseline sum of target lesion diameters was statistically significantly correlated with worsening of OS. Conclusions: Overall results in this SCLC population suggest tarlatamab exposures associated with the recommended dose of 10 mg Q2W exhibited near maximal efficacy and a favorable benefit-risk profile. None of the evaluated patient-specific covariates resulted in clinically meaningful changes in efficacy or safety, and therefore do not warrant a dose adjustment. Citation Format: Po-Wei Chen, Mukul Minocha, Stephanie M. Kong, Erik S. Anderson, Amanda Parkes, Pablo Martinez, Brett E. Houk, Chih-Wei Lin. Exposure-efficacy and exposure-safety relationships of tarlatamab to inform dose selection and benefit-risk assessment in patients with advanced small cell lung cancer (SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7164.

Abstract 7167: Impact of patient specific factors on exposures of tarlatamab, a half-life extended DLL3-directed bispecific T-cell engager in patients with advanced small cell lung cancer

Abstract Background: Tarlatamab is a first in class, half-life extended delta-like ligand (DLL3) targeted bispecific T-cell engager (BiTE) immunotherapy that has shown antitumor activity with durable objective responses and promising survival outcomes in the ongoing studies in patients with previously treated small-cell lung cancer (NCT03319940, NCT05060016) (Ahn et al, 2023; Paz-Ares et al, 2023). Here we describe the effects of patient specific factors [age, sex, bodyweight, ethnicity, estimates of renal and hepatic function, prior lines of therapy, baseline disease status, emergence of anti-drug antibodies (ADA)] on tarlatamab exposures. Methods: Tarlatamab serum concentrations were available from 420 subjects (8509 samples) pooled across the ongoing Phase 1 DeLLphi-300 study (dose range 0.003 mg to 100 mg Q2W and 200 mg Q3W) and Phase 2 DeLLphi-301 study (10 mg and 100 mg Q2W). The data were analyzed using a nonlinear-mixed effects modeling approach implemented in NONMEM (v7.5) software. Model selection and evaluation was guided by standard statistical and graphical approaches. Impact of key baseline demographic variables on tarlatamab clearance and volume of distribution were evaluated. Results: Tarlatamab exposures increased in a dose-proportional manner and were not impacted by age, sex, ethnicity, estimates of renal and hepatic function, prior lines of therapy or baseline disease status. Asian race resulted in 14% higher peak serum concentrations relative to Caucasian subjects. Higher body weight (99 kg; 90th percentile) was associated with a 24% decrease in Day 28 pre-dose concentration (Ctrough) relative to median bodyweight (73 kg). Lower body weight (54 kg; 10th percentile) was associated with a 27% increase in Ctrough relative to median bodyweight. Positive ADA status resulted in a 24% decrease in Ctrough. However, at the recommended dose of 10 mg Q2W, neither body weight nor ADA status had a clinically relevant impact on tarlatamab efficacy or safety measures (Ahn et al, 2023). Conclusion: Overall, based on these analyses, no dose adjustment for tarlatamab is required based on age, sex, bodyweight, ethnicity, estimates of renal and hepatic function, prior lines of therapy, baseline disease status or emergence of ADA. Citation Format: Stephanie M. Kong, Mukul Minocha, Po-Wei Chen, Pablo Martinez, Erik S. Anderson, Amanda Parkes, Brett E. Houk, Chih-Wei Lin. Impact of patient specific factors on exposures of tarlatamab, a half-life extended DLL3-directed bispecific T-cell engager in patients with advanced small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7167.

Comparison of the efficacy and safety of anlotinib monotherapy or anlotinib plus immune checkpoint inhibitor for advanced small cell lung cancer with brain metastases.

Anlotinib, as a salvage treatment for patients after failure of third-line or later-line treatments for small cell lung cancer (SCLC), has shown efficacy in patients with brain metastases (BMs). However, the efficacy and safety of anlotinib alone or in combination with immunotherapy for SCLC with BMs remain unclear. Patients treated with anlotinib alone or in combination with an immune checkpoint inhibitor (ICI) at the Zhejiang Cancer Hospital between April 2019 and February 2023 were identified. Kaplan-Meier curves were used to describe the progression-free survival (PFS) and intracranial PFS (iPFS). A waterfall diagram was used to indicate changes in intracranial lesions. A total of 48 patients were included; 29 received anlotinib alone, and 19 were administered anlotinib plus ICI. Combination therapy, compared with anlotinib, was associated with significantly longer PFS and iPFS (PFS: 8.1months vs. 2.5months, P < 0.001; iPFS: 8.1months vs. 2.5months, P = 0.004). Similar results were observed in patients with multiple BMs (PFS: 8.1months vs. 1.9months, P = 0.001; iPFS: 8.1months vs. 1.9months, P = 0.002). After third-line or later-line treatments, patients treated with ICI plus anlotinib also achieved significant PFS and iPFS benefits (PFS: 8.4months vs. 2.1months, P < 0.001; iPFS: 9.2months vs. 2.1months, P = 0.002). No new or severe adverse events were observed with combination therapy. The combination of anlotinib and ICI has promising intracranial and extracranial efficacy with tolerable toxicity, and may be a therapeutic option for SCLC patients with BMs.

The inhibitory effect of apatinib on different small cell lung cancer cells and in lung cancer-bearing mice and patients.

To observe the inhibitory effect of the small molecule tyrosine kinase inhibitor apatinib on small cell lung cancer in vitro and vivo. Three small lung cancer cells were selected CCK-8 and monoclonal assay was used to determine the effect of apatinib on proliferation. The effects on cell cycle and apoptosis were detected by flow cytometry and TUNEL. We observed the inhibitory effect of different doses of apatinib on xenograft tumor. The efficacy and safety of apatinib in 20 patients with advanced small cell lung cancer were observed. For small cell lung cancer with high expression of VEGFR2, apatinib has a significant inhibitory effect both in vitro and in vivo. It can play an inhibitory role by promoting apoptosis and cell cycle arrest pathways. For small cell lung cancer with low expression of VEGFR, the inhibitory effect on cells in vitro was not significant. It has certain inhibitory effect on nude mouse transplanted tumor and small cell lung cancer patients, but the effect is weaker than that of animal models and patients with small cell lung cancer cells with high expression of VEGFR2. Apatinib has a significant inhibitory effect on small cell lung cancer with high expression of VEGFR2 and may be a treatment for small cell lung cancer patients.

Systemic immune index predicts tumor-infiltrating lymphocyte intensity and immunotherapy response in small cell lung cancer.

Despite recent progresses in immune checkpoint blockade (ICB) in small-cell lung cancer (SCLC), a lack of understanding regarding the systemic tumor immune environment (STIE) and local tumor immune microenvironment (TIME) makes it difficult to accurately predict clinical outcomes and identify potential beneficiaries from ICB therapy. We enrolled 191 patients with stage I-III SCLC and comprehensively evaluated the prognostic role of STIE by several quantitative measurements, and further integrate it with a local immune score system (LISS) established by eXtreme Gradient Boosting (XGBoost) machine learning algorithm. We also test the value of STIE in beneficiary selection in our independent advanced SCLC cohort receiving programmed cell death 1 ligand 1 (PD-L1) blockade therapy. Among several systemic immune markers, the STIE as assessed by prognostic nutritional index (PNI) was correlated with disease-free survival (DFS) and overall survival (OS), and remained as an independent prognostic factor for SCLC patients [hazard ratio (HR): 0.473, 95% confidence interval (CI): 0.241-0.929, P=0.030]. Higher PNI score was closely associated with inflamed SCLC molecular subtype and local tumor-infiltrating lymphocytes (TILs). We further constructed a LISS which combined top three important local immune biomarkers (CD8+ T-cell count, PD-L1 expression on CD8+ T-cell and CD4+ T-cell count) and integrated it with the PNI score. The final integrated immune risk system was an independent prognostic factor and achieved better predictive performance than Tumor Node Metastasis (TNM) stages and single immune biomarker. Furthermore, PNI-high extensive-stage SCLC patients achieved better clinical response and longer progression-free survival (PFS) (11.8 vs. 5.9 months, P=0.012) from PD-L1 blockade therapy. This study provides a method to investigate the prognostic value of overall immune status by combining the PNI with local immune biomarkers in SCLC. The promising clinical application of PNI in efficacy prediction and beneficiary selection for SCLC immunotherapy is also highlighted.

Prognostic significance of pretreatment albumin–bilirubin (ALBI) grade and platelet–albumin–bilirubin (PALBI) grade in patients with small cell lung cancer

Small cell lung cancer (SCLC) is a common cancer among the world’s lung cancers. Despite advances in diagnosis and treatment, the prognosis is still poor. There is no effective biomarker other than stage in daily practice. However, in daily practice, patients may have different features and survival times even though they have the same stage. Previously, albumin–bilirubin (ALBI) grade, platelet–albumin–bilirubin (PALBI) grade were used to determine the prognosis of acute-chronic liver failure and acute upper gastrointestinal bleeding in liver cirrhosis. In subsequent studies, they were found to be associated with prognosis in hepatocellular carcinoma (HCC) and other solid cancers. However, the prognostic relationship between ALBI grade, PALBI grade, and SCLC is unknown. Therefore, we conducted this study to examine the relationship between ALBI grade and PALBI grade and prognosis in SCLC patients. Data of 138 patients with advanced SCLC at diagnosis between 2009 and 2020 were analyzed retrospectively. The results of the multivariate analysis were as follows: ALBI grade 1 vs 2, hazard ratio (HR) = 1.608, p = 0.002 for OS and HR = 1.575, p = 0.002 for PFS; ALBI grade 1 vs 3, HR = 2.035, p < 0.001 for OS and HR = 2.675, p < 0.001 for PFS; PALBI grade 1 vs 2, HR = 1.302, p = 0.006 for OS and HR = 1.674, p = 0.002 for PFS; and PALBI grade 1 vs 3, HR = 1.725, p < 0.001 for OS and HR = 2.675, p < 0.001 for PFS. In conclusion, the ALBI and PALBI grades were determined to be associated with the prognosis of SCLC, and they can be used as easy, inexpensive, and practical markers in determining the follow-up treatment and prognosis of SCLC patients.

Intensity-modulated proton and carbon-ion radiotherapy using a fixed-beam system for locally advanced lung cancer: dosimetric comparison with x-ray radiotherapy and normal tissue complication probability (NTCP) evaluation

Objective. To assess the dosimetric consequences and the normal tissue complication probability (NTCP) for the organs at risk (OARs) in intensity-modulated particle radiotherapy of proton (IMPT) and carbon-ion (IMCT) using a fixed-beam delivery system when compared with intensity-modulated photon radiotherapy (IMRT) for locally advanced small-cell lung cancer. Approach. The plans were all designed under the same total relative biological effectiveness (RBE)-weighted prescription dose, in which the planning target volume (PTV) of the internal gross target volume(IGTV) and the PTV of the clinical target volume was irradiated with 69.3 Gy (RBE) and 63 Gy (RBE), respectively, using a simultaneously integrated boosting (SIB) technique. NTCPs were estimated for heart, lung, esophagus and spinal cord by Lyman–Kutcher–Burman (LKB) and logistic models. Dose escalation was simulated under the desired NTCP values (0.05, 0.10 and 0.50) of the three radiation techniques. Main results. Under the similar target coverage, almost all OARs were significantly better spared (p < 0.05) when using the particle radiotherapy except for D1cc (the dose to 1 cm3 of the volume) of the proximal bronchial tree (p > 0.05). At least 57.6% of mean heart dose, 28.8% of mean lung dose and 19.1% of mean esophageal dose were reduced compared with IMRT. The mean NTCP of radiation-induced pneumonitis (RP) in the ipsilateral lung was 0.39 ± 0.33 (0.39 ± 0.31) in IMPT plans and 0.36 ± 0.32 (0.35 ± 0.30) in IMCT plans compared with 0.66 ± 0.30 (0.64 ± 0.28) in IMRT plans by LKB (logistic) models. The target dose could be escalated to 78.3/76.9 Gy (RBE) in IMPT/IMCT plans compared with 61.7 Gy (RBE) in IMRT plans when 0.50 of NTCP in terms of RP in the ipsilateral lung was applied. Significance. This study presents the potential of better control of the side effects and improvement of local control originating from the dosimetric advantage with the application of IMPT and IMCT with the SIB technique for locally advanced lung cancer, even with limited beam directions.

Evaluating Oral Probiotic Supplements as Complementary Treatment in Advanced Lung Cancer Patients Receiving ICIs: A Prospective Real-World Study.

To evaluate the effectiveness of oral probiotic supplements in patients undergoing immune checkpoint inhibitors (ICIs) for the treatment of advanced lung cancer. This prospective real-world study enrolled patients with advanced lung cancer who were receiving ICIs as part of their treatment. The patients were divided into 2 groups: Group OPS received oral probiotic supplements along with ICIs, while Group C did not. The primary endpoint was progression-free survival (PFS). The secondary outcome measure was the objective response rate (ORR). A total of 253 patients were included in the study, with 71 patients in Group OPS and 182 patients in the control group (Group C). No significant differences were observed in the median PFS between the 2 groups for all patients. However, for small cell lung cancer (SCLC) patients, the median PFS was significantly better in the Group OPS compared to the Group C (11.1months vs 7.0months, P = .049). No significant differences were observed in median PFS for the non-small cell lung cancer (NSCLC) cohort between the 2 groups, but a trend towards better median PFS in Group OPS was noticed (16.5months vs 12.3months, P = .56). The ORR for the entire cohort was 58.0%. Oral probiotics supplements in combination with ICIs included regimen may improve the outcome in patients with advanced SCLC. The above points should be proved by further study.

Comparison of Efficacy and Safety of Second-Line Treatment Options for Advanced Small-Cell Lung Cancer: A Retrospective Analysis.

As monotherapy such as topotecan has reached a plateau of effectiveness, new second-line treatments based on experience have been used in clinical application. This study compared the efficacy and safety of different second-line treatments for advanced small-cell lung cancer (SCLC). A total of 380 patients with advanced SCLC were screened selectively in the retrospective study. Adverse events and patient responses were assessed using Common Terminology Criteria for Adverse Events v5.0 and Response Evaluation Criteria for Solid Tumors v1.1. The progression-free survival (PFS) was estimated using the Kaplan-Meier method or Cox survival regression model and compared using the log-rank test. In the platinum-resistant group, disease control rate (DCR) and median PFS (mPFS) were prolonged in the combination group versus single-agent group (DCR: 49.24% vs 24.39%, P = .004; mPFS: 3.73 vs 1.90 months, P < .001). Grade 3/4 toxicity was similar between the 2 groups (P = .683). The mPFS did not differ among single-agent groups (P = .380). No significant difference was observed in mPFS of different combination therapy groups (P = .170). In terms of platinum-based chemotherapy, the DCR and mPFS were prolonged in irinotecan-platinum group versus taxol-platinum group (DCR: 56.14% vs 9.09%, P = .004; mPFS: 3.87 vs 1.93 months, P = .012). Grade 3/4 toxicity was similar between the 2 groups (P = .614). The mPFS was prolonged in the chemotherapy plus immunotherapy group versus single-agent chemotherapy group (P = .003). In the platinum-sensitive group, the mPFS did not differ between the combination group and single-agent group (P = .200). The mPFS did not differ among different single-agent groups (P = .260) or combination groups (P = .150). There was no difference in mPFS among different platinum-based chemotherapy groups (P = .830). For patients with platinum-resistant SCLC, combination therapy has shown better efficacy and acceptable toxicity profile than monotherapy. Among combination therapies, irinotecan-platinum has shown better efficacy than taxol-platinum. For patients with platinum-sensitive SCLC, the efficacy of different single-agent or combination therapies was similar.

A Multicenter Study Assessing the Real-World Use and Effectiveness of First-Line Chemotherapy Plus Immunotherapy in Advanced Small-Cell Lung Cancer (SCLC) Patients

BackgroundFirst-line chemotherapy plus immunotherapy (CT-IO) has recently demonstrated survival benefits over CT alone in extensive-stage small-cell lung cancer (ES-SCLC), based on randomized phase III studies. This retrospective multicenter study assessed the real-world use and effectiveness of CT-IO in ES-SCLC patients. Patients and MethodsAll newly diagnosed ES-SCLC patients from 4 French hospitals treated with CT alone or CT-IO between May 2020 and December 2021 were included. Overall survival (OS) and real-world progression-free survival (rwPFS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were performed to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs) in univariate and multivariate models. The aim was not to compare efficacy between groups. ResultsAmong 104 patients, 75 (72.1%) received CT-IO. Brain metastases were diagnosed in 28.3% of patients, and 29.8% were performance status (PS) ≥ 2. At a median follow-up of 16.8 months (95%CI, 14.9-23.4), the median OS was 11.4 months (95%CI, 7.7-14.7) in the CT-IO group, and the 12-month OS rate was 43.6% (95%CI, 33.3-57.2). In the CT group, the median OS was 7.8 months (95%CI, 5.4-11.8) and the 12-month OS rate was 15.3% (95%CI, 5.7-41.0). In multivariate analyses, baseline brain and liver metastases were associated with a shorter OS for patients treated in the CT-IO group (HR, 3.80 [95%CI, 1.90-7.60] and 3.12 [95%CI, 1.60-6.08] respectively; P < 0.001 for both). ConclusionWe showed that clinicians have chosen to use IO beyond the specific criteria defined in guidelines. Survival data appeared promising with a median OS comparable to the one previously demonstrated in clinical trials.

PPIs therapy has a negative impact on the clinical outcomes of advanced SCLC patients treated with PD-L1 inhibitors

BackgroundProgrammed death-ligand 1 (PD-L1) inhibitors has emerged as a first-line therapeutic strategy for advanced small cell lung cancer (SCLC), which can stimulate T-cell activation, thereby preventing tumor avoidance of immunologic surveillance, whereas, proton pump inhibitors (PPIs) can play an important role in regulating immune function. This study assessed whether the concomitantly use of PPIs affected outcomes of immunotherapy in advanced SCLC.MethodsData from advanced SCLC patients who firstly treated with PD-L1 inhibitors between July 2018 and February 2021 was retrospectively analyzed. The impact of concomitant medications (especially PPIs) on objective response rate, progression-free survival (PFS) and overall survival (OS) were evaluated.ResultsOf 208 patients, 101 received immunotherapy concomitant PPIs. The median PFS of patients receiving PPIs (6.6 months) were significantly shorter than those without PPIs (10.6 months), and so was OS. There was associated with a 74.9% increased risk of progression and 58.3% increased risk of death. Both first-line and post-first-line immunotherapy, patients treated PPIs had poorer PFS.ConclusionPPIs therapy has a negative impact on the clinical outcomes of advanced SCLC patients treated with PD-L1 inhibitors.

Comparative analysis of using atezolizumab vs. durvalumab in combination with platinum-containing chemotherapy in adult patients with advanced small cell lung cancer

Background. In recent decades, a course of chemotherapy with etoposide (EP) and platinum preparations (сarboplatinum, CP) has been recommended as a standard first-line treatment option in patients with advanced small cell lung cancer (SCLC), but with the advent of new immunological drugs, immune checkpoint inhibitors, approaches to therapy have changed. Based on randomized clinical trials, courses combining traditional platinum-containing chemotherapy with inhibitors of programmed death-ligand 1 (PD-L1) atezolizumab (ATZ) or durvalumab (Durv) have been included in many clinical recommendations for oncologists.Objective: to evaluate the clinical and cost-effectiveness of using ATZ and Durv as first-line therapy in advanced SCLC adult patients within the Russian healthcare system.Material and methods. The model of treatment of advanced SCLC adult patients in conditions of the healthcare system of the Russian Federation included the most popular options for first-line immunochemotherapy: CP/EP + ATZ and CP/EP + Durv courses. Pharmacoeconomic cost-effectiveness analysis, sensitivity analysis of the selected model to changes in its initial parameters, budget impact analysis were carried out.Results. The total medical costs for CP/EP + ATZ course (2,310,546.07 rubles) were significantly lower than for the CP/EP + Durv course (4,081,833.98 rubles). With comparable costs for the treatment of complications (426,175.17 and 407,704.50 rubles, respectively), the cost of Durv exceeded ATZ by 94.8%. When conducting a cost-effectiveness analysis, the advantage was retained by the CP/EP + ATZ course, the cost-effectiveness ratios for which amounted to 187,849.27 rubles per month of patient's life and 444,335.78 rubles per month of patient's life without progression (for CP/EP + Durv, 316,421.24 and 800,359.60 rubles, respectively). When choosing the CP/ET + ATZ strategy, the savings will be 128,571.96 rubles per month of life and 356,023.82 rubles per month of life without progression. Sensitivity analysis demonstrated the stability of the developed model: to increase in the price of the CP/EP + ATZ course up to +68%; to decrease in overall survival with the course of CP/EP + ATZ up to –40%; to decrease in progression-free survival with the course of CP/EP + ATZ to –44%. Budget impact analysis showed that with a possible cohort size of 4,448 people an increase in the proportion of patients receiving CP/EP + ATZ course from 70% to 90% will reduce budget costs by 1,575,737,725.38 rubles per year, which will allow additional treatment of 681.9 advanced SCLC patients per year (+15.3%).Conclusion. The use of ATZ combined with standard platinum-containing chemotherapy in advanced SCLC adult patients as the first-line therapy is clinically and cost-effective strategy within the Russian healthcare system, as it allows to reduce therapy costs compared to Durv and treat more SCLC patients, which fully corresponds to the target indicators of the federal program “Oncology”.

524P Treatment pattern and overall survival by lines of therapy among patients with advanced small cell lung cancer in Taiwan

524P Treatment pattern and overall survival by lines of therapy among patients with advanced small cell lung cancer in Taiwan

Evaluation of Real-Life Chemoimmunotherapy Combination in Patients with Metastatic Small Cell Lung Carcinoma (SCLC): A Multicentric Case-Control Study.

The current first-line standard treatment for advanced small cell lung cancer (SCLC) is a combination of chemotherapy and immunotherapy. However, few efficacy data are available in a real-life settings, including frail patients. The aim of this study is to describe the real-life efficacy of chemoimmunotherapy in an unselected SCLC population. We conducted a retrospective multicenter study, which compared two cohorts of patients with treatment-naive metastatic SCLC treated in six academic centers in the Greater Paris area. Cohort 1 included patients treated with chemotherapy between January 2017 and December 2018, and cohort 2 included patients treated with chemoimmunotherapy between January 2019 and December 2020. A total of 153 consecutive patients were included (cohort 1: n = 96; cohort 2: n = 57). Clinical characteristics were similar between the two cohorts. Overall survival (OS) was statistically higher in cohort 2 (median survival 15.47 months) than in cohort 1 (median survival 9.5 months) (p = 0.0001). OS for patients with a performance status ≥2 and for patients ≥70 years old was not statistically different between the two cohorts. Chemoimmunotherapy efficacy was better compared to chemotherapy alone in case of brain or liver metastases. In conclusion, the combination of chemoimmunotherapy in metastatic SCLC appears to provide a real-life OS benefit. Dedicated clinical trials are needed to test this strategy in patients with impaired performance status or advanced age.

Lung immune prognostic index as a prognostic predictor in patients with advanced small cell lung cancer

Aims: Identifying prognostic markers in advanced small-cell lung cancer (A-SCLC) patients is important. Therefore, our study aimed to evaluate the prognostic value of pretreatment lung immune prognostic index (LIPI) in A-SCLC.&#x0D; Methods: This was a retrospective and observational study of A-SCLC patients treated with platinum plus etoposide chemotherapy as first-line treatment. The association of LIPI with progression-free survival (PFS) and overall survival (OS) was analysed.&#x0D; Results: One hundred eighteen patients were included in this study and divided into three groups LIPI 0 (n=27, 22.9%), LIPI 1 (n=57, 48.3%) and LIPI 2 (n=34, 28.8%). The median PFS of LIPI groups (0/1/2) was 8.9 (95% CI 3.83-13.96), 8 (95% CI 6.41-9.58), and 5.6 (95% CI 4.60-6.60) months, respectively (p=0.1) The median OS of LIPI groups (0/1/2) was 12 (95% CI 9.11-14.88), 10.1 (95% CI 9.16-11.03), and 7.7 (95% CI 6.55-8.84) months, respectively (p=0.02). Cox regression analysis revealed that LIPI 2 score was an independent risk factor for both PFS (HR 1.839, 95% CI: 1.075-3.144, p=0.02) and OS (HR 1.757, 95% CI: 1.006-3.071, p=0.04).&#x0D; Conclusion: LIPI score can be used as a simple and easily accessible marker to predict prognosis for A-SCLC patients.

In-Vivo Somatostatin-Receptor Expression in Small Cell Lung Cancer as a Prognostic Image Biomarker and Therapeutic Target.

Given the dismal prognosis of small cell lung cancer (SCLC), novel therapeutic targets are urgently needed. We aimed to evaluate whether SSTR expression, as assessed by positron emission tomography (PET), can be applied as a prognostic image biomarker and determined subjects eligible for peptide receptor radionuclide therapy (PRRT). A total of 67 patients (26 females; age, 41-80 years) with advanced SCLC underwent SSTR-directed PET/computed tomography (somatostatin receptor imaging, SRI). SRI-avid tumor burden was quantified by maximum standardized uptake values (SUVmax) and tumor-to-liver ratios (T/L) of the most intense SCLC lesion. Scan findings were correlated with progression-free (PFS) and overall survival (OS). In addition, subjects eligible for SSTR-directed radioligand therapy were identified, and treatment outcome and toxicity profile were recorded. On a patient basis, 36/67 (53.7%) subjects presented with mainly SSTR-positive SCLC lesions (>50% lesions positive); in 10/67 patients (14.9%), all lesions were positive. The median SUVmax was found to be 8.5, while the median T/L was 1.12. SRI-uptake was not associated with PFS or OS, respectively (SUVmax vs. PFS, ρ = 0.13 with p = 0.30 and vs. OS, ρ = 0.00 with p = 0.97; T/L vs. PFS, ρ = 0.07 with p = 0.58 and vs. OS, ρ = -0.05 with p = 0.70). PRRT was performed in 14 patients. One patient succumbed to treatment-independent infectious complications immediately after PRRT. In the remaining 13 subjects, disease control was achieved in 5/13 (38.5%) with a single patient achieving a partial response (stable disease in the remainder). In the sub-group of responding patients, PFS and OS were 357 days and 480 days, respectively. SSTR expression as detected by SRI is not predictive of outcome in patients with advanced SCLC. However, it might serve as a therapeutic target in selected patients.

Anlotinib plus irinotecan or docetaxel in small-cell lung cancer (SCLC) relapsed within six months: Updated results from a single-arm, phase Ⅱ study.

e20629 Background: There is still no unsatisfactory treatment strategy for patients (pts) with advanced SCLC relapsed within six months after first-line treatment, although chemotherapy alone is the standard treatment. Anlotinib, an oral multitarget tyrosine kinase inhibitor, effectively inhibits angiogenesis and enhances tumor cell response to chemotherapy. In the ALTER 1202 trial, anlotinib had significantly improved progression-free survival (PFS) and overall survival (OS) of advanced SCLC pts who received at least two lines chemotherapy. Therefore, we presented the updated efficacy and safety of anlotinib plus irinotecan or docetaxel in SCLC relapsed within six months after first-line treatment. Methods: Eligible pts with advanced SCLC who have relapsed within six months after first-line platinum-based treatment received anlotinib (12mg, QD from day 1 to 14 of a 21-day cycle, the dose could be adjusted to 10mg or 8mg according to the patient's tolerance) and irinotecan (65mg/m2, day1,8, q3w, up to 4 cycles) or docetaxel (60mg/m2, q3w, up to 4 cycles) until progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included PFS, the disease control rate (DCR), OS and safety. Results: As of Jan 31, 2023, we recruited 39 pts, among which 36 pts (median age: 63.2 years, male: 86.1%, ECOG PS 1: 80.6%, brain metastasis: 58.3%, liver metastasis: 36.1%) were eligible for efficacy analysis. Median follow-up time was 17.2 months (95% Cl, 8.27 -26.13 ). Of 36 evaluable pts, 1 pts had complete response (CR) , 20 pts reached partial response (PR) and 11 pts had stable disease(SD). The ORR was 58% (21/36) and the DCR was 89% (32/36), respectively. The median PFS was 4.4 months (95%Cl: 3.73- 5.08). The median OS was 7.9 months (95%Cl: 5.28-10.52). The Progression-free survival and overall survival in patients with recurrence &gt; 3 months and ≤ 6 months (PFS 6.5 m and OS 11.9 m) after first-line therapy improved more significantly than in patients with recurrence ≤ 3 months (PFS 4.1 m and OS 5.9 m). Most common grade 1-2 treatment-related adverse events (TRAEs) included weakness(58.3%), anorexia(38.9%), anemia(25%), hypertension (15.6%), Oral mucositis (13.9%) and leucopenia (11.1%). 3 pts (8.3%) suffered from grade 3 AEs, which were thrombocytopenia, leukopenia, and anemia. Conclusions: Anlotinib combined with irinotecan or docetaxel as second-line treatment for non-sensitive recurrent SCLC (i.e., extensive-stage disease time to relapse: 0-6 months) showed superior efficacy and safety compared with standard chemotherapy. It may become a novel therapeutic strategy for the population. Clinical trial information: NCT04757779 .

Clinical outcomes of intra-arterial chemotherapy combined with iodine-125 seed brachytherapy in the treatment of malignant superior vena cava syndrome caused by small cell lung cancer

PurposeCurrently there is a lack of effective treatment strategies for malignant superior vena cava syndrome (SVCS). We aim to investigate the therapeutic effect of intra-arterial chemotherapy (IAC) combined with the Single Needle Cone Puncture method for the 125I brachytherapy (SNCP-125I) in treating SVCS caused by stage III/IV Small Cell Lung Cancer (SCLC). Materials and methodsSixty-two patients with SCLC who developed SVCS from January 2014 to October 2020 were investigated in this study. Out of these 62 patients, 32 underwent IAC combined with SNCP-125I (Group A) and 30 patients received IAC treatment only (Group B). Clinical symptom remission, response rate, disease control rate, and overall survival of these two groups of patients were analyzed and compared. ResultsThe remission rate of symptoms including dyspnea, edema, dysphagia, pectoralgia, and cough of malignant SVCS in Group A was significantly higher than that in Group B (70.5 and 50.53%, P=0.0004, respectively). The disease control rates (DCR, PR+CR+SD) of Group A and B were 87.5 and 66.7%, respectively (P=0.049). Response rates (RR, PR+CR) of Group A and Group B were 71.9 and 40% (P=0.011). The median overall survival (OS) of Group A was significantly longer than that in Group B which was 18 months compared to 11.75 months (P=0.0360). ConclusionsIAC treatment effectively treated malignant SVCS in advanced SCLC patients. IAC combined with SNCP-125I in the treatment of malignant SVCS caused by SCLC showed improved clinical outcomes including symptom remission and local tumor control rates than IAC treatment only in treating SCLC-induced malignant SVCS.