Extensive Small Cell Lung Cancer Research Articles

Cholecystokinin-2 receptor targeting by [68Ga]Ga-DOTA-MGS5 PET/CT in a patient with extensive disease small cell lung cancer.

Cholecystokinin-2 receptor targeting by [68Ga]Ga-DOTA-MGS5 PET/CT in a patient with extensive disease small cell lung cancer.

Trilaciclib: A Novel Approach to Mitigate Chemotherapy-Induced Myelosuppression in Cancer Treatment

AbstractTrilaciclib, a novel cyclin-dependent kinase 4/6 inhibitor, has demonstrated the ability to protect bone marrow from chemotherapy toxicity, improving patients' quality of life (QoL). This review describes the mechanism of action, efficacy, and toxicity profile of trilaciclib. Trilaciclib halts retinoblastoma protein phosphorylation during the early G1 phase, preventing the transition from the G1/S phase and inducing the cell cycle arrest in the G1 phase, which protects the hematopoietic cell lineages. Trilaciclib is indicated by the United States Food and Drug Administration and National Comprehensive Cancer Network to decrease the incidence of chemotherapy-induced myelosuppression in adult patients before a platinum/etoposide or topotecan containing regimen for extensive stage small cell lung cancer. Its ease of administration as an intravenous infusion, given before starting chemotherapy, and the favorable side effect profile make it a better-tolerated drug, improving patient QoL.

Study Design and Rationale for IFCT- 2203 TAXIO: A study that aims to evaluate the effectiveness of a first-line chemotherapy regimen without etoposide, combined with durvalumab, for patients with extensive disease Small Cell Lung Cancer.

BackgroundStudies have shown improvement in overall survival with anti-PD1/PD-L1 molecules in combination with cisplatin/carboplatin and etoposide as a first-line treatment for Small Cell Lung Cancer (SCLC). However, first-line efficacy remains limited and well below that observed in Non-Small Cell Lung Cancer (NSCLC). Etoposide may have a detrimental effect on lymphocyte activation, which could explain the limited benefit of immunotherapy in the first line and the lack of benefit in the second line for patients previously exposed to high levels of etoposide. MethodsWe initiated a multicenter, single-arm, open-label phase II study of a chemotherapy regimen with durvalumab, combined with carboplatin and paclitaxel for extensive disease SCLC. Eligible patients will receive durvalumab plus carboplatin and paclitaxel every 3 weeks for up to 4 cycles, followed by durvalumab every 4 weeks until progression or unacceptable toxicity. A total of 67 patients will be enrolled in this study, with a 12-month enrollment period and 36-month follow-up. The primary endpoint is Overall Survival (OS) rate at 12 months. Secondary endpoints are best response rate, OS, OS at 24- and 36 months, progression free survival (PFS), duration of response, quality of life and safety. ResultsThis study aims to establish the efficacy of durvalumab combined with carboplatin and paclitaxel in patients with extensive disease Small Cell Lung Cancer. Clinical trial registrationEU CT: 2023-504670-38-00.

Exploring effective biomarkers and potential immune related gene in small cell lung cancer

Small cell lung cancer (SCLC) is well known as a highly malignant neuroendocrine tumor. Immunotherapy combined with chemotherapy has become a standard treatment for extensive SCLC. However, since most patients quickly develop resistance and relapse, finding new therapeutic targets for SCLC is important. We obtained four microarray datasets from the Gene Expression Omnibus database and screened differentially expressed genes by two methods: batch correction and “RobustRankAggregation”. After the establishment of a protein–protein interaction network through Cytoscape, seven hub genes (AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, and AURKA) with high expression in SCLC samples were obtained by eight CytoHubba algorithms. The Least Absolute Shrinkage and Selection Operator regression and the Wilcoxon test were used to analyze the differences in the immune cells’ infiltration between normal and SCLC samples. The contents of seven kinds of immune cells were considered to differ significantly between SCLC samples and normal samples. A negative association was found between BIRC5 and monocytes in the correlation analysis between immune cells and the seven hub genes. The subsequent in vitro validation of experimental results showed that downregulating the expression of BIRC5 by siRNA can promote apoptotic activity of SCLC cells and inhibit their vitality, migration, and invasion. The use of BIRC5 inhibitor inhibited the vitality of SCLC cells and increased their apoptotic activity. BIRC5 may be a novel therapeutic target option for SCLC.

Metabolic Tumor Volume as Significant Predictor for Chemotherapy Containing PD-L1 Blocker in Extensive Stage Small Cell Lung Cancer.

Chemo-immunotherapy, including the programmed death ligand 1 (PD-L1) antibody, is an effective treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, no biomarker has been established for the prediction of chemo-immunotherapy. Therefore, we investigated the potential of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) as a predictive marker. Forty-six patients with ES-SCLC who received 18F-FDG-PET immediately before combined platinum-based chemotherapy with PD-L1 blockade as a first-line treatment were eligible, and the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18F-FDG uptake were evaluated. PD-L1 and tumor infiltrative lymphocytes (TILs) were immunohistochemically analyzed in 36 of the 46 patients. A high MTV was significantly associated with poor performance status and low albumin levels, and there was a significant association between low albumin and high TLG. Univariate analysis identified sex, Brinkman index, and MTV as significant predictors of progression-free survival (PFS), and sex, SUVmax, MTV, and TLG as significant factors of overall survival (OS). Multivariate analysis revealed that sex, Brinkman index, and MTV were independent prognostic factors for PFS, and sex, SUVmax, MTV, and TLG were significant predictors of OS. SUVmax was significantly higher in patients with positive PD-L1 expression than in those with negative expression but was not significantly different between positive and negative TILs. Moreover, the levels of MTV and TLG were not closely associated with the levels of PD-L1 and TILs. MTV or TLG metabolic tumor activity is suitable for the prediction of chemo-immunotherapy outcomes in patients with ES-SCLC.

Abstract 5098: Second-line treatment outcomes in Extensive Stage Small Cell Lung Cancer (ES-SCLC) patients after first-line immuno-chemotherapy

Abstract Background: First-line immune checkpoint inhibitors (ICIs) has significantly improved overall survival (OS) of ES-SCLC. However, second-line treatment options are still controversial with limited overall survival. This study aims to evaluate the efficacy of different second-line regimens for relapsed ES-SCLC after first-line immuno-chemotherapy. Patients and Methods: We retrospectively reviewed 96 ES-SCLC patients receiving first-line immuno-chemotherapy in Cancer Hospital Chinese Academy of Medical Sciences, from Jan 2019 to Dec 2022. Clinical data were collected from electronic medical records. The clinical outcomes, including objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier method and standard log-rank test. Results: From January 4, 2019 to December 18, 2022, a total of 96 ES-SCLC patients received first-line immuno-chemotherapy and 49 of them went through second-line treatment in our center. Patient characteristics were listed as follows : median age 63 (31-79), male 76 (79.2%) , heavy smoker 59 (61.5%), liver metastasis 40 (41.7%), brain metastasis 33 (34.4%) and refractory recurrence 58 (60.4%). Second-line treatments included immunotherapy crossover and combination with chemotherapy (n=40), anlotinib with or without chemotherapy (n=5), chemotherapy alone (n=4). ORR of the whole group in the second-line setting was 22.4%. Median PFS was 3.23 months (95% CI 1.96-4.50). Cross-line immunotherapy failed to improved survival for relapsed ES-SCLC compared with those without ICIs ( mPFS 3.23 vs 3.13m, p=0.829). Anlotinib based treatment showed numerically superior PFS for relapsed SCLC compared with those without anlotinib therapy (mPFS 6.00 vs 3.13m, p=0.089). Conclusion: This retrospective study indicated cross-line ICIs failure to improve clinical outcome for relapsed ES-SCLC, and implied the potential benefits of anlotinib in second-line setting. Citation Format: Rui Wan, Linjie Fan, Jia Zhong, Jianchun Duan, Zhijie Wang, Xuezhi Hao, Jie Wang. Second-line treatment outcomes in Extensive Stage Small Cell Lung Cancer (ES-SCLC) patients after first-line immuno-chemotherapy [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 5098.

Sintilimab plus anlotinib as second or further-line therapy for extensive disease small cell lung cancer: a phase 2 investigator-initiated non-randomized controlled trial

Treatment options remain rather limited for extensive disease small cell lung cancer (ED-SCLC) patients in second or further-line setting. The phase 2 investigator-initiated non-randomized study enrolled patients who had disease progression on at least one line of platinum-based chemotherapy. Participants received intravenous sintilimab 200mg on day one and oral daily anlotinib 12mg on days 1-14 once every three weeks per cycle. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. This study is registered with ClinicalTrials.gov (NCT04055792). Forty-two patients were enrolled between August 29, 2019 and December 26, 2021at Henan Cancer Hospital in China. 37 patients were evaluable for efficacy. The median follow-up was 24.8 months (IQR: 16.9-28.2). The median PFS was 6.1 months (95% CI: 5.0-7.3). The OS was 12.7 months (95% CI: 7.1-18.2). The ORR was 56.8% (21/37, 95% CI: 40.0-73.5) and the DCR was 89.2% (33/37, 95% CI: 78.7-99.7). Forty patients (40/42, 95%) had at least one treatment-related adverse event (TRAE). Immune-related adverse events (irAEs) were reported in 39 patients (39/42, 93%), while grade 3 or higher irAEs occurred in 11 patients (11/42, 26%). The most frequent irAEs were hypothyroidism (16/42, 38%), elevated gamma-glutamyl transpeptidase (15/42, 36%) and elevated creatine kinase MB (15/42, 36%). The most frequent grade 3 or higher irAEs were elevated gamma-glutamyl transpeptidase (5/42, 12%) and increased aspartate aminotransferase (3/42, 7%). Sintilimab plus anlotinib demonstrated promising antitumor activities as second or further-line therapy for ED-SCLC and had manageable toxicities. The findings support further randomized controlled trials of this combination regimen for ED-SCLC. Henan Province Health and Youth Subject Leader Training Project, Henan Health Science and Technology Innovation Talents, ZHONGYUAN QIANREN JIHUA, Henan International Joint Laboratory of drug resistance and reversal of targeted therapy for lung cancer, Tumor Research Fund of Anti-Angiogenesis Targeted Therapy of China Anti-Cancer Association.

A Single-Arm Multi-Center Phase II Clinical Trial of Cadonilimab (anti-PD-1/CTLA-4) in Combination with or without Conventional Second-Line Treatment for Patients with Extensive Stage Small Cell Lung Cancer.

Cadonilimab (AK104) is a bispecific IgG-single-chain Fv fragment (ScFv) antibody that binds to PD-1 and CTLA-4. Cadonilimab has shown encouraging anti-tumour activity and a favourable safety profile in several tumour types. In second-line treatment, there is no defined standard of care for patients with extensive-stage small-cell lung cancer (ES-SCLC). Cadonilimab is expected to show substantial clinical efficacy. To assess the antitumor activity and safety of cadonilimab monotherapy or combination with conventional therapy in ES-SCLC patients who failed first-line treatment. In this multicenter, open-label, phase II study, ES-SCLC patients who had failed first-line treatment, also aged 18 years to 70 years with histologically or cytologically confirmed ES-SCLC, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2 were eligible. Patients will receive cadonilimab 10 mg/kg every three weeks (Q3 W) among 24 months until progressive disease (PD) or adverse events (AE) discovery. The primary endpoint is progression-free survival (PFS). NCT05901584.

Serum CYFRA 21-1 Level as a Prognostic Marker for Extensive Disease Small Cell Lung Cancer.

Pretreatment serum cytokeratin 19 fragment (CYFRA21-1) level predicts outcomes in patients with non-small cell lung cancer; however, little is known about the clinical value of serum CYFRA21-1 level in patients with small cell lung cancer (SCLC). The aim of this study was to evaluate the prognostic value of pretreatment serum CYFRA21-1 level in patients with extensive disease (ED)-SCLC treated using platinum-doublet chemotherapy. We retrospectively analyzed the pretreatment serum CYFRA21-1 levels of patients with ED-SCLC who were treated using first-line platinum-doublet chemotherapy. A total of 98 patients were analyzed. The patients with a high CYFRA21-1 level (≥7.0 ng/ml) (n=29) had significantly shorter progression-free survival (PFS) and overall survival (OS) than the patients with low CYFRA21-1 levels (n=67) [median PFS=118 days vs. 125 days, respectively (p=0.018); median OS=213 days vs. 295 days, respectively (p=0.046)]. In addition, high CYFRA21-1 level was associated with a high refractory relapse rate. Serum CYFRA21-1 level may be a prognostic marker for patients with ED-SCLC treated with platinum-doublet chemotherapy.

Relationship between patterns of immunohistochemical conventional neuroendocrine markers and efficacy of immune check point inhibitors in patients with extensive disease small cell lung cancer.

Which patients benefit from the addition of immune checkpoint inhibitors (ICIs) to chemotherapy for small cell lung cancer (SCLC) remains unclear. There have been few reports on the efficacy of ICIs based on conventional immunohistochemical neuroendocrine (NE) markers (synaptophysin, chromogranin A, and neural cell adhesion molecule [NCAM]). In the present study, we aimed to analyze the relationship between the expression of immunohistochemical NE markers and the efficacy of ICIs in patients with extensive disease (ED)-SCLC, to assess whether conventional NE markers are predictive of ICIs. Patients with untreated ED-SCLC who received first-line therapy at the Shizuoka Cancer Center between November 2002 and July 2021 were retrospectively reviewed. We evaluated the efficacy of first-line chemotherapy according to the expression status of each immunohistochemical NE marker in patients treated with ICI plus chemotherapy (ICI-chemo group) and with chemotherapy alone (chemo group). A total of 227 patients were included in the ICI-chemo and chemo groups, respectively. The progression-free survival (PFS) tended to be better in patients in the ICI-chemo group than those treated with chemotherapy alone in patients with NE marker-positive SCLC. In particular, it was statistically significant in patients with chromogranin A-positive SCLC (p = 0.036). In patients with NE marker-negative SCLC, no significant differences were observed in PFS between the two groups. There were no significant differences in overall survival (OS), regardless of the expression of any conventional NE marker. Our study suggests that the efficacy of ICIs in addition to chemotherapy may be poor in patients with NE marker-negative SCLC.

Phase II study of frontline maintenance rucaparib in combination with nivolumab in extensive stage small cell lung cancer

Phase II study of frontline maintenance rucaparib in combination with nivolumab in extensive stage small cell lung cancer

Treatment of Brain Metastasis of Small Cell Lung Cancer with PD-1 Inhibitor: A Case Report

PD-L1 (Programmed Cell Death Protein L1) inhibitor has been used in the first-line treatment of extensive small cell lung cancer, but its prognosis is still poor and its survival time is short, especially in patients with brain metastasis. The effect of PD-1 inhibitor is not satisfactory as well. PD-1 (Programmed Cell Death Protein 1) inhibitors are less effective and used in the third-line treatment, and patients only experience short PSF benefit. Herein, we report a unique case of a patient with brain and adrenal metastases of small cell lung cancer for whom brain metastases partially disappeared, efficacy evaluation at 25 months follow - up PR, quality of life was good, and no significant adverse effects were observed after receiving comprehensive treatment with PD-1 inhibitor Toripalimab.

EE360 Clinical and Economic Evaluation of Atezolizumab Versus Durvalumab Administration in Adult Patients with Extensive Stage Small Cell Lung Cancer

EE360 Clinical and Economic Evaluation of Atezolizumab Versus Durvalumab Administration in Adult Patients with Extensive Stage Small Cell Lung Cancer

Assessment of hospitalizations and cytopenia events among patients with extensive stage small cell lung cancer (ES-SCLC) receiving chemotherapy with trilaciclib.

531 Background: Prior studies have reported that that nearly 75% of patients receiving chemotherapy for small cell lung cancer present a hospitalization associated with myelosuppression. Trilaciclib is a myeloprotective agent indicated for use prior to chemotherapy in ES-SCLC. Given the relative recency in trilaciclib approval (2/12/2021), this study assessed real-world outcomes associated with trilaciclib among patients with ES-SCLC. Methods: This study was a retrospective analysis of adult ES-SCLC patients diagnosed between 2020 and 2023 using the 100% Medicare Fee-for-Service and MORE2 Registry claims databases. Eligible patients met literature-based criteria for ES-SCLC using International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes, received platinum/etoposide- or topotecan-based chemotherapy regimens after diagnosis, and were continuously enrolled ≥ 30 days preceding and following chemotherapy initiation. Patients were categorized into 2 mutually exclusive cohorts: 1) trilaciclib administered at chemotherapy initiation and with no granulocyte colony stimulating factor (G-CSF) received during chemotherapy, and 2) no trilaciclib administered during chemotherapy. Chi-square tests and student’s t-tests were used to assess statistically significant differences between groups on cytopenia events (based on the appearance of an ICD-10 diagnosis code) and all-cause hospitalizations during the post-index period. Data use agreements prohibit reporting of categorical outcomes of < 11 patients. Results: 132 trilaciclib (mean age 70.6, male 50.8%) and 12,305 non-trilaciclib patients (age 68.0, male 48.2%) were eligible for the study; median follow-up was 202 days. Compared to the non-trilaciclib cohort, patients receiving trilaciclib had a lower rate of hospitalizations per patient per month during follow-up (0.14±0.25 vs. 0.19±0.27; p <0.001). Within 90 days post-chemotherapy initiation, trilaciclib was associated with lower rates of hospitalization (21.2% vs. 32.4%; p <0.01) and febrile neutropenia (< 3% vs. 5.7%, p=0.01). Anemia (44.7% vs. 52.6%, p=0.07), neutropenia (9.1% vs. 14.9%, p=0.06) and thrombocytopenia (5.3% vs. 8.4%, p=0.2) were numerically lower for trilaciclib patients in the 90-day post-index period. Results were similar when the non-trilaciclib group was stratified by prophylactic G-CSF usage. Conclusions: This real-world study demonstrated that receiving trilaciclib prior to chemotherapy treatment was associated with a lower rates of hospitalizations and cytopenia events, suggesting trilaciclib may prevent adverse events associated with treatment for ES-SCLC.

EP13.03-12 Prophylactic Cranial and Consolidation Thoracic Radiation in Extensive Stage Small Cell (ES-SCLC) Lung Cancer in the Chemo-immunotherapy Era

EP13.03-12 Prophylactic Cranial and Consolidation Thoracic Radiation in Extensive Stage Small Cell (ES-SCLC) Lung Cancer in the Chemo-immunotherapy Era

EP13.06-03 Real-World Outcomes in Patients with 3rd-Line Extensive Stage Small Cell Lung Cancer

EP13.06-03 Real-World Outcomes in Patients with 3rd-Line Extensive Stage Small Cell Lung Cancer

EP13.05-01 Early ctDNA Changes and Clinical Outcomes in Extensive Stage Small Cell Lung Cancer Patients on Nivolumab and Temozolomide

EP13.05-01 Early ctDNA Changes and Clinical Outcomes in Extensive Stage Small Cell Lung Cancer Patients on Nivolumab and Temozolomide

EP13.01-02 Patient-Specific Factors as Prognostic Biomarkers in Extensive Disease SCLC

EP13.01-02 Patient-Specific Factors as Prognostic Biomarkers in Extensive Disease SCLC

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer.

The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited. We retrospectively assessed the real-world efficacy and safety of atezolizumab in addition to carboplatin and etoposide (EP + A), versus carboplatin and etoposide (EP) alone in previously untreated ED-SCLC patients. From a total of 99 patients, 46 were assigned to the EP + A group, and 53 to the EP group. No significant difference was observed in progression-free survival between the groups. However, the overall survival (OS) was significantly longer in the EP + A group (20.8 vs 12.1months; HR: 0.52; p = 0.0127). Patients older than 70years, male, with performance status 0-1, without liver metastasis, and low levels of C-reactive protein and neutrophil-lymphocyte ratio, experienced longer OS in the EP + A group compared to the EP group. The addition of atezolizumab to the platinum doublet regimen significantly extended OS in ED-SCLC patients, particularly among certain subgroups, suggesting its potential value in personalized treatment strategies. Further investigation is warranted to validate these findings.

Clinical study of antinib combined with radiotherapy in the treatment of third-line extensive small cell lung cancer

Objective: To explore whether the survival benefit of the third-line extensive small-cell lung cancer (ES-SCLC) will be obtained by the combination of anlotinib and radiotherapy, and evaluate the safety of this treatment regimen. Methods: Twenty-seven patients with ES-SCLC who received third-line treatment with less than three metastatic organs at the Cancer Hospital of Xinjiang Medical University from November 2018 to July 2021 were collected and treated with radiotherapy based on anlotinib. Kaplan-Meier curve was used to estimate the overall survival (OS) and progression-free survival (PFS), descriptive statistical analysis was used to evaluate the safety, and European organisation for research and treatment of cancer quality of life questionnaire-core 30 (EORTC QLQ-C30) was used to evaluate the quality of life. Results: The follow-up cut-off date was July 1, 2021, and the follow-up time ranged from 4.8 to 31.0 months, with a median follow-up time of 10.2 months for the entire group. Among the 27 patients, 4 achieved partial remission, 17 had stable disease and 6 had progression of disease. The objective remission rate (ORR) was 14.8%, and the disease control rate (DCR) was 77.8%. Median PFS and the median OS were 5 months and 11 months, respectively. The most common adverse reactions included fatigue (33.3%, 9/27), anorexia (14.8%, 4/27), bleeding (14.8%, 4/27) and hand-foot syndrome (11.1%, 3/27). Most of them were grade 1 to grade 2, 3 cases were more than grade 3, and there was no grade 5 toxicity recorded. After radiotherapy combined with amlotinib treatment, patients showed improvement in general health, somatic functioning, social functioning, and emotional functioning (all P<0.05). Conclusion: For the third-line ES-SCLC patients, radiotherapy based on the anlotinib can significantly prolong their PFS and OS, and the adverse reactions can be tolerated.