Current status and future perspectives of immune checkpoint inhibitors in extensive-stage small cell lung cancer

Small-cell lung cancer (SCLC) is a type of neuroendocrine neoplasms with high aggressiveness and poor prognosis. Chemotherapy has been the standard first-line therapy for SCLC over the past several decades. In recent years, results of randomized phase III CASPIAN and IMpower-133 trials indicated that the combination of immune checkpoint inhibitors (ICIs) with platinum-etoposide chemotherapy improved the overall survival (OS) of patients with extensive stage small-cell lung cancer (ES-SCLC), which has transformed the treatment model for ES-SCLC. ICIs combined with chemotherapy has become the new first-line standard treatment of ES-SCLC with the latest research results from CASPIAN and ASTRUM-005 studies. This review summarizes the recent progress of ICIs in the treatment of ES-SCLC and expounds the mode and efficacy of immunotherapy for ES-SCLC. Future research focused on exploring basic SCLC biology and identifying novel predictive biomarkers in response to ICIs in ES-SCLC is essential. Double-ICIs treatment strategies, bispecific antibodies, and ICIs combined with other therapies, such as chemotherapy, radiotherapy, and targeted therapy, represent a new modality and show great promise for the treatment of ES-SCLC, which should achieve greater therapeutic effects through multiple synergistic mechanisms.     

伊立替康联合顺铂方案对照依托泊甙联合顺铂方案治疗广泛期小细胞肺癌疗效的回顾性分析

目的回顾性分析比较伊立替康联合顺铂方案和依托泊甙联合顺铂方案治疗广泛期小细胞肺癌的近期疗效和毒性反应。方法收集2006年1月一2010年10月43例小细胞肺癌患者的病历资料,其中18例采用IP方案治疗．25例采用EP方案治疗。统计分析两种方案的近期疗效及不良反应。结果IP方案组与EP方案组的有效率分别为50％和48％,差异无显著性。IP方案组的Ⅲ-Ⅳ度腹泻和Ⅲ一Ⅳ度恶心呕吐发生率分别为17％和ll％,EP方案组发生率分别为4％和8％．差异亦均无显著性。但IP方案组的Ⅲ-Ⅳ度骨髓抑制发生率为11％,明显低于EP方案组（40％）。结论IP方案和EP方案治疗广泛期小细胞肺癌的疗效相当,但IP方案的血液学毒性较EP方案明显减轻．不失为治疗广泛期小细胞肺癌的一线治疗选择。     

Clinical outcomes of atezolizumab in combination with etoposide/platinum for treatment of extensive-stage small-cell lung cancer: A real-world,multicenter, retrospective,controlled study in China

ObjectiveAtezolizumab along with chemotherapy has prolonged the survival of patients with extensive-stage small-cell lung cancer (ES-SCLC) worldwide, although real-world (RW) data are lacking in China. This study was designed to evaluate the efficacy and clinical outcomes of atezolizumab plus etoposide/platinum (EP).MethodsData obtained in this retrospective study were captured from six oncology units of five medical facilities from January 2019 to April 2022. For first-line treatments, atezolizumab combined with EP vs. EP alone, we primarily evaluated progression-free survival (PFS); other efficacy indicators, including overall survival (OS), objective response rate (ORR), and patterns of SCLC progression and adverse events (AEs) were assessed.ResultsThe primary analysis included data from 225 patients, of whom 133 received EP along with atezolizumab (atezolizumab group) and 92 received EP alone (EP group). The PFS duration of the atezolizumab group [7.10 months; 95% confidence interval (95% CI), 6.53−9.00] exceeded that of the EP group (6.50 months; 95% CI, 4.83−7.53). Overall, the hazard ratio (HR) was 0.69 (95% CI, 0.49−0.97) (P=0.029); particularly, the HR was 0.54 (95% CI, 0.36−0.80) among patients undergoing ≥4 chemotherapy cycles and 0.33 (95% CI, 0.20−0.56) among individuals with atezolizumab maintenance. The ORR and disease-control rate (DCR) were similar between the two groups. Because of incomplete OS data, the median OS was not determined for either group. Bone marrow suppression was the most common AE detected (58.6%) in the atezolizumab group. Immune-related AEs occurred in 19 patients in the atezolizumab group (14.3%), with only one case of grade 3 encephalitis.ConclusionsThis RW study in China demonstrated improved clinical outcomes of atezolizumab along with EP for ES-SCLC, particularly in the chemosensitive population. These results align with the results of the IMpower133 study, although the impact of this treatment modality on OS warrants additional follow-up studies.     

Influence of tumor response on the survival of patients with extensive-stage small-cell lung cancer treated with the etoposide plus cisplatin chemotherapy regimen

Objective In this study, we evaluated the difference of progression-free survival(PFS) and overall survival(OS) between extensive-stage small-cell lung cancer(ES-SCLC) patients who acquired partial response(PR) or complete remission(CR) after two cycles of first-line chemotherapy with the etoposide plus cisplatin(EP) regimen and those who acquired PR or CR after four or six cycles.Methods A total of 106 eligible patients treated with the EP chemotherapy regimen for two to six cycles, at The General Hospital of Shenyang Military Region(China) between November 2004 and May 2011, were enrolled in this study. RECIST version 1.1 was used for the evaluation of chemotherapy efficiency. We followed up all eligible patients every 4 weeks. All statistical data were analyzed by using SPSS 21.0 statistical package for Windows.Results After a median follow-up of 293 days(range, 62–1531 days), all patients had died by the cutoff date. Fifty-one patients acquired PR or CR after two cycles of chemotherapy; the median PFS reached 6.0 months(95% CI, 5.1–6.9), and the median OS was 10.5 months(95% CI, 8.6–12.4). Twenty-eight patients acquired PR or CR after four or six cycles; the median PFS was 4.8 months(95% CI, 4.4–5.2), and the median OS was 7.5 months(95% CI, 6.8–8.2). Both PFS and OS showed a statistical difference between the two groups. Conclusion ES-SCLC patients who acquired PR or CR after two cycles of the EP regimen as first-line therapy had longer PFS and OS than those who acquired PR or CR after four or six cycles.     

Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer

Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m-2 was administered on days 1 and 8 and cisplatin 60 mg m-2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0-82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer.     

Sarcopenia defined by skeletal muscle mass index at the third lumbar vertebra is a prognostic factor for extensive-stage small cell lung cancer patients: a retrospective study

BackgroundSmall cell lung cancer (SCLC) is one of the most aggressive types of lung cancer and reliable indicators are needed for improved patient management. The evaluation of skeletal muscle index of the third lumbar vertebra (L3MI) based on computed tomography (CT) is used to estimate patient prognosis in multiple cancers. However, its function in extensive-stage SCLC remains controversial. Considering that the maintenance of muscle mass may affect the survival of cancer patients. Herein, a retrospective study was conducted to investigate whether sarcopenia defined by skeletal muscle mass index at the third lumbar vertebra is a prognostic factor in extensive-stage SCLC cancer patients.MethodsThis retrospective analysis included extensive-stage SCLC patients diagnosed at the Sun Yat-sen University Cancer Center from January 2009 to March 2017 with platinum-based chemotherapy. Clinical data were collated for further examination, and CT or positron emission tomography (PET)/CT datasets were analyzed for body mass index (BMI) and L3MI. Follow-up data were collected by contacting patients or their families. Overall survival (OS) was defined as the interval between the date of treatment started and the date of death or censoring. The Kaplan-Meier product limit method and log-rank tests were used to assess differences in OS between the high L3MI and low L3MI groups. Cox regression analysis was used to identify independent factors of OS.ResultsFor the 139 extensive-stage SCLC patients, the median follow-up time was 26.1 months (range, 0.4 to 79.4 months). The median OS was 9.5 months. There were no differences in age, inflammatory factors, nor progression after first-line treatment between the high L3MI and low L3MI groups. Kaplan-Meier analysis showed that the OS of the high L3MI group was significantly longer than that of the low L3MI group (14.045 vs. 9.985 months; P=0.007), and multivariate analysis identified high L3MI to be an independent prognostic factor for predicting longer OS in extensive-stage SCLC patients [hazard ratio (HR), 0.623; 95% confidence interval (CI), 0.405–0.960; P=0.032].ConclusionsSarcopenia defined by L3MI is a prognostic factor for extensive-stage SCLC patients and early intervention of muscle mass maintaining may achieve better cancer management.