Extensive Stage Small Cell Lung Research Articles

Prior antibiotics, proton pump inhibitors, and probiotics in patients with extensive stage small cell lung cancer treated with immune checkpoint blockade: A post-hoc analysis of the phase I/III IMpower 133 trial.

The potential impact of concomitant medications such as systemic antibiotics, proton pump inhibitors (PPIs), and probiotics in patients with extensive-stage small cell lung cancer (ES-SCLC) receiving first-line chemo-immunotherapy combinations remains unclear. We ran a post hoc analysis of the IMpower133 phase I/III trial, which randomized patients with ES-SCLC to receive carboplatin/etoposide with either atezolizumab or placebo for 4 cycles, followed by maintenance therapy. We included any systemic antibiotic/probiotic exposure within 42 days prior to treatment initiation and any PPIs treatment within 30 days prior to treatment initiation. We explored the potential prognostic impact of antibiotics, PPIs and probiotics across the atezolizumab/chemotherapy and placebo/chemotherapy arms including the multivariable interaction term between the treatment modality and antibiotics/PPIs/probiotics. The analysis included 198 patients in the atezolizumab/chemotherapy arm and 195 in the placebo/chemotherapy arm. Baseline clinic-pathologic features were well balanced between the two cohorts, with 17 (8.6%) and 14 (7.2%) patients on antibiotics, 43 (21.7%) and 55 (28.2%) on PPIs, and 3 (1.5%) and 5 (2.6%) on probiotics among the atezolizumab/chemotherapy and placebo/chemotherapy cohorts, respectively. Exposure to antibiotics, PPIs, or probiotics was not associated with overall survival or progression free survival in either cohort. Furthermore, interaction terms between these medications and treatment modalities were not statistically significant. Baseline use of antibiotics, PPIs or probiotics did not influence clinical outcomes in patients with ES-SCLC treated with first-line atezolizumab/placebo plus chemotherapy, suggesting that they may not have a notable impact on clinical outcomes and could be considered for use in this patient population when necessary.

Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era

IntroductionThe role of consolidative thoracic and prophylactic brain radiation for extensive stage small cell lung cancer patients is controversial. We investigated the factors associated with the use of any radiation therapy (RT) and whether RT has a benefit to overall survival (OS) in patients receiving any systemic therapy and whether this benefit is the same if Chemotherapy (CT) or chemo-immunotherapy (CT-IO) is used. Material/MethodsThe NCDB database was queried from years 2017–2019. Patients receiving systemic therapy- STX (CT or CT-IO) had to have at least 6 months of follow-up and have no brain metastases at diagnosis. All RT patients had to receive upfront systemic therapy, be treated 2–6 months from diagnosis, and if treated to the brain received 25 Gy in 10 fractions only. Multi-variable analyses (MVA) were used to determine factors associated with OS and selection for any radiation. Propensity matching for factors affecting OS were used to generate Kaplan-Meier OS curves. Log-rank tests were used to determine differences in Kaplan Meier survival curves for the effects of RT on OS. ResultsThe total number of patients receiving RT/STX or STX alone as well as their median follow-up (months) were (890, 17.0 mn) and (6898, 14.0mn). The median time to the start of STX and RT were 22.9 days and 152 days, respectively. MVA noted that RT had a greater effect on OS (Thorax, Brain, Both Brain/Thorax – HRs = 0.80, 0.77, 0.70) than other interventions including IO (HR 0.87) and palliative care without RT (HR 1.06). Selection for radiation depended significantly upon factors affecting OS (HR) including lack of liver metastases, females, age and Charlson co-morbidity index, but did not depend upon insurance status, race, or county income/high school graduation rates. Propensity-score matched OS curves noted the same significant effects of RT on OS in those receiving CT +/- IO, CT-IO, and CT alone with HRs of 0.68/0.68/0.68 for thoracic RT, 0.72/0.72/0.70 for brain RT, and 0.60/0.60/0.60 for brain/thoracic RT, respectively. ConclusionsThe patient with extensive stage small cell lung cancer who reach candidacy and receive RT may have a significant improvement in OS compared to the patients treated only with CT or CT-IO. Combined thoracic and prophylactic brain RT seems to be better than either one alone. The impact of radiation whether given to one or two sites may be more beneficial than immunotherapy added to chemotherapy.

Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer. S1929

To evaluate whether the addition of a poly (ADP-ribose) polymerase inhibitor (PARPi) talazoparib to maintenance immune checkpoint inhibitor (ICI) atezolizumab following frontline chemoimmunotherapy improved outcomes in patients with Schlafen 11 (SLFN11)-positive extensive stage small cell lung cancer (ES-SCLC). Patients with newly diagnosed SLFN11 expressing (H-score ≥ 1, evaluated centrally) ES-SCLC were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) following frontline chemotherapy plus atezolizumab. The primary objective was to compare progression-free survival (PFS) using a 1-sided 10% level stratified log-rank test. Secondary endpoints included objective response rate (ORR), overall survival (OS), and toxicity. Target sample size was 84 eligible patients. From June 15, 2020 to December 15, 2022, 106 eligible patients were randomized (54 to AT and 52 to A). PFS was improved with AT versus A (hazard ratio [HR], 0.66; 80% confidence interval [CI]: 0.50-0.86; 1-sided P = 0.019) with a median PFS of 2.9 and 2.4 months; OS was not different between groups (HR, 0.98; 80% CI: 0.71-1.36; 1-sided P = 0.47). Grade ≥ 3 non-hematologic treatment-related adverse events (TRAEs) occurred in 17% of patients with AT and 14% of patients with A. Grade ≥ 3 hematological TRAEs were more common in AT (50%) than in A (4%) (P < 0.001). Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.

OA04.06 Efficacy and Safety of HS-20093 in Extensive Stage Small Cell Lung Cancer in A Multicenter, Phase 1 Study (ARTEMIS-001)

OA04.06 Efficacy and Safety of HS-20093 in Extensive Stage Small Cell Lung Cancer in A Multicenter, Phase 1 Study (ARTEMIS-001)

OA04.04 Sacituzumab Govitecan as Second-Line Treatment in Patients with Extensive Stage Small Cell Lung Cancer

OA04.04 Sacituzumab Govitecan as Second-Line Treatment in Patients with Extensive Stage Small Cell Lung Cancer

MA17.08 Safety and Efficacy of Tifcemalimab Combined with Toripalimab in Refractory Extensive Stage Small Cell Lung Cancer

MA17.08 Safety and Efficacy of Tifcemalimab Combined with Toripalimab in Refractory Extensive Stage Small Cell Lung Cancer

P1.13B.01 Lurbinectedin vs. Platinum Rechallenge in Extensive Stage Small Cell Lung Cancer after Platinum Doublet, A Multicenter Retrospective Study

P1.13B.01 Lurbinectedin vs. Platinum Rechallenge in Extensive Stage Small Cell Lung Cancer after Platinum Doublet, A Multicenter Retrospective Study

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

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.

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.

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.

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)

1011: Thoracic radiotherapy and PCI in extensive stage small cell lung cancer following chemoimmunotherapy

1011: Thoracic radiotherapy and PCI in extensive stage small cell lung cancer following chemoimmunotherapy

Clinical efficacy and safety of immune checkpoint inhibitors plus anlotinib as secondline or subsequent therapy in extensive stage small cell lung cancer: a retrospective study.

Treatments are limited for extensive stage small cell lung cancer (ES-SCLC) patients in secondline or subsequent setting. This study aimed to explore the clinical efficacy and safety of immune checkpoint inhibitors (ICIs) plus anlotinib as secondline or subsequent therapy in ES-SCLC. We retrospectively analyzed 116 patients with ES-SCLC at Shandong Provincial Qianfoshan Hospital between January 2019 and March 2024. According to the different therapy regimes, they were divided into three groups, ICI plus anlotinib as secondline or subsequent therapy group (ICI + anlotinib group), single ICI as secondline or subsequent therapy group (single ICI therapy group), single chemotherapy as secondline therapy group (single chemotherapy group). Kaplan-Meier method was used to compare the progression-free survival (PFS) and the overall survival time (OS) among these three groups. Cox regression analysis was used to analyze different factors which correlated to PFS and OS. The adverse events were assessed according to the Common Terminology Criteria for Adverse Events version 5.0. Kaplan-Meier analysis showed that patients in ICI + anlotinib group had a longer PFS and OS compared to patients in single ICI therapy group (median PFS [mPFS]: 6.7months vs. 4.6months, P = 0.007; median OS [mOS]:12.4months vs. 8.4months, P = 0.041) and single chemotherapy group (mPFS: 6.7months vs. 3.0months, P < 0.001; mOS: 12.4months vs. 7.2months, P = 0.002). The Cox regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), liver metastasis, brain metastasis and treatment regimes were independent predictors that affecting the PFS and OS of all the enrolled patients. The common adverse events (AEs) were wleukopenia and fatigue. There was no significant statistical difference in other AEs among the three groups except for leukopenia. ICI + anlotinib as secondline or subsequent therapy has better efficacy than single ICI group and single chemotherapy group and with tolerable toxicities for patients with ES-SCLC.

Efficacy of Apatinib Combined with Etoposide for Maintenance Therapy in Extensive Stage Small Cell Lung Cancer

Objective: To investigate the efficacy, safety and survival of apatinib combined with etoposide for maintenance therapy in extensive stage small cell lung cancer (ES-SCLC). Method: A total of 70 patients with extensive stage small cell lung cancer after standard chemo-radiotherapy who were admitted to Tangshan people’s Hospital from January 2019 to February 2023 were enrolled and then grouped into the observation group and the control group by random number table method, with 35 patients in each group. Patients from the observation group received apatinib combined with oral etoposide capsules for maintenance therapy. Patients from the control group received etoposide capsules for maintenance chemotherapy. The clinical efficacy and adverse reactions of these two groups were compared, and the 6-month and 1-year survivals were followed up. Results: The objective response rate (ORR) and disease control rate (ODC) of the observation group were higher than those of the control group [37.1% (13 / 35) vs. 17.1% (6 / 35), 65.7% (23 / 35) vs. 40% (14 / 35)], and the differences were statistically significant (all p&lt;0.05). There was no significant difference in the incidence of adverse reactions between these two groups (p&gt;0.05). The 6-month and 1-year survival rates of the observation group were significantly higher than those of the control group, and the differences were statistically significant (all p&lt;0.05). Conclusion: Apatinib combined with etoposide capsules applied for maintenance therapy in extensive stage small cell lung cancer could provide improved clinical efficacy and survival rate of patients, with tolerable adverse reactions.

DNA damage response signatures are associated with frontline chemotherapy response and routes of tumor evolution in extensive stage small cell lung cancer.

A hallmark of small cell lung cancer (SCLC) is its recalcitrance to therapy. While most SCLCs respond to frontline therapy, resistance inevitably develops. Identifying phenotypes potentiating chemoresistance and immune evasion is a crucial unmet need. Previous reports have linked upregulation of the DNA damage response (DDR) machinery to chemoresistance and immune evasion across cancers. However, it is unknown if SCLCs exhibit distinct DDR phenotypes. To study SCLC DDR phenotypes, we developed a new DDR gene analysis method and applied it to SCLC clinical samples, in vitro , and in vivo model systems. We then investigated how DDR regulation is associated with SCLC biology, chemotherapy response, and tumor evolution following therapy. Using multi-omic profiling, we demonstrate that SCLC tumors cluster into three DDR phenotypes with unique molecular features. Hallmarks of these DDR clusters include differential expression of DNA repair genes, increased replication stress, and heightened G2/M cell cycle arrest. SCLCs with elevated DDR phenotypes exhibit increased neuroendocrine features and decreased "inflamed" biomarkers, both within and across SCLC subtypes. Treatment naive DDR status identified SCLC patients with different responses to frontline chemotherapy. Tumors with initial DDR Intermediate and DDR High phenotypes demonstrated greater tendency for subtype switching and emergence of heterogeneous phenotypes following treatment. We establish that SCLC can be classified into one of three distinct, clinically relevant DDR clusters. Our data demonstrates that DDR status plays a key role in shaping SCLC phenotypes, chemotherapy response, and patterns of tumor evolution. Future work targeting DDR specific phenotypes will be instrumental in improving patient outcomes.

Advances in thoracic consolidation radiotherapy after first-line immunotherapy combined with chemotherapy for extensive stage small cell lung cancer

Small cell lung cancer (SCLC) accounts for about 13%~17% of primary bronchial lung cancer. Due to its rapid growth rate, aggressive behavior, early metastasis and poor prognosis, about 70% of patients were diagnosed with extensive-stage (ES) disease. Although most ES-SCLC patients are sensitive to initial chemotherapy, local recurrence and distant metastasis develop in the short term. Immunotherapy has brought the dawn to overcome it. At present, immune checkpoint inhibitor combined with chemotherapy has become an important strategy as first-line therapy for ES-SCLC. Nevertheless, patients are still at a high risk of chest lesion recurrence after initial systemic therapy. Whether the addition of thoracic consolidation radiotherapy (TRT) can reduce chest lesion recurrence rate remains to be determined. In this review, we summarized the latest research progress in the mode of first-line chemotherapy combined with immunotherapy followed by TRT in ES-SCLC, aiming to provide reference for clinical practice.

Tumor mutational burden adjusted by neutrophil-to-lymphocyte ratio serves as a potential biomarker for atezolizumab-treated patients with extensive stage small cell lung cancer

BackgroundThere is a desperate for the identification of more accurate and efficient biomarkers for ICI responses in patients with SCLC.MethodsThe data of our study was obtained from IMpower133 study. A total of 202 patients with SCLC received the treatment of placebo plus carboplatin plus etoposide (EC) while a total of 201 patients with SCLC received the treatment of atezolizumab plus EC. Overall survival (OS) was compared using Kaplan Meier analyses. Univariate and multivariate Cox regression analysis were used to determine independent prognostic variables affecting OS in patients with SCLC.ResultsWe have demonstrated that a higher TMB adjusted by a lower neutrophil-to-lymphocyte ratio (NLR) is significantly correlated with improved OS, in patients with SCLC subject to either atezolizumab or placebo (P = 0.001 for atezolizumab and P = 0.034 for placebo). Moreover, Cox model showed that TMB < 10 mut/Mb adjusted by NLR ≥ median was an independent factor of OS for atezolizumab-treated SCLC patients (hazard ratio [HR], 2.82; 95% confidence interval; 1.52–5.24; P = 0.001). Both univariate and multivariate cox regression analysis showed that for patients with SCLC harboring low NLR and high TMB, survival is significantly longer in those treated with atezolizumab than those treated with placebo. Survival benefit is significantly higher in atezolizumab-treated patients with SCLC than those treated with placebo (P = 0.018 for TMB cutoff = 10 mut/Mb, P = 0.034 for TMB cutoff = 16 mut/Mb).ConclusionOur findings provide a promising insight into the utility of NLR-adjusted TMB in the prognosis and immune responses in patients with SCLC.

Results of a phase III clinical trial with anti-PDL1 treatment in combination with chemotherapy for extensive stage small cell lung cancer.

8095 Background: In China, small cell lung cancer (SCLC) accounts for over 15% of lung cancers. The morbidity of SCLC has been continuously increasing. SCLC is invasive, fast-growing cancer that distinctly differs from other cancers. Approximately 70% of cases present with metastasis at diagnosis and the median overall survival rate is about 8 to 11 months with a 5-year survival rate of less than 5%. Although being sensitive to chemotherapy and radiotherapy, SCLC patients are liable to relapse and often present with drug resistance. Here we study the combination of Socazolimab, an anti-PDL1 antibody, carboplatin and etoposide to treat extensive stage small cell lung cancer. Methods: The study is a randomized, double-blinded, placebo-controlled multicenter Phase III clinical trial. Patients who have extensive-stage SCLC are eligible to the trial. Patients are randomly assigned to the study group (Socazolimab + carboplatin + etoposide) or control group (placebo + carboplatin + etoposide) at 1:1 ratio, with a treatment cycle of every 3 weeks. There are 4 cycles of chemotherapy followed by Socazolimab or placebo alone until termination events occurred or for up to 2 years. The primary endpoint is overall survival (OS). The major secondary endpoint is progression free survival (PFS). Results: There were a total of 498 patients recruited for the study with average age of 61.9 amount which 449 patients were diagnosed with stage IV SCLC. All the analysis was based on intent-to-treat (ITT). The median baseline performance status score was 1.0. The median OS of study group and control group are 13.90 months (95% CI: 12.22-15.34) and 11.58 months (95% CI: 10.64-12.81) respectively, with a P-value of 0.0316. The 24 month survival rate of study group and control group are 20.7% (95% CI:14.8-27.3) and 5.9 %(95% CI: 0.8-18.9). The median PFS of the two groups are 5.55 months (95% CI:5.06-5.82) and 4.37 months (95% CI: 4.27-4.70) with a P-value &lt; 0.0001. The treatment related adverse event were similar in both groups. Conclusions: These results show that Socazolimab plus chemotherapy continued to provide clinically meaningful improvements in OS for patients with extensive stage small cell lung cancer. Clinical trial information: NCT04878016 .