Untreated Small Cell Lung Cancer Research Articles

Abstract CT255: AdvanTIG-204: A phase 2, multicenter, randomized, 3-arm, open-label study investigating the preliminary efficacy and safety of ociperlimab (anti-TIGIT) + tislelizumab (anti-PD-1) + concurrent chemoradiotherapy (cCRT) in patients with untreated limited-stage small cell lung cancer (SCLC)

Abstract Background: Despite a high response rate to cCRT, patients with limited-stage SCLC generally experience recurrence of disease after a few months and survival remains poor. Immunotherapy has shown benefit in many tumor types, including SCLC. In preclinical and clinical studies of solid tumors, co-inhibition of T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitor motif domains (TIGIT) and PD-1 enhanced antitumor activity of anti-PD-1. AdvanTIG-204 (NCT04952597) investigated the efficacy and safety of ociperlimab + tislelizumab + cCRT in patients with untreated limited-stage SCLC. Methods: Patients with limited-stage SCLC and no prior systemic therapy were randomized 1:1:1 to Arm A (ociperlimab [900 mg IV Q3W] + tislelizumab [200 mg IV Q3W] + cCRT for 4 cycles, then ociperlimab + tislelizumab), Arm B (tislelizumab + cCRT for 4 cycles, then tislelizumab), or Arm C (cCRT for 4 cycles). Study drugs (Arms A and B) were continued for up to 12 months or until progression, unacceptable toxicity, or withdrawal. Primary endpoint: investigator-assessed PFS per RECIST v1.1. Secondary analyses included additional efficacy and safety endpoints in the ITT population, and efficacy in patient subgroups by PD-L1 and TIGIT expression (both <1% vs ≥1%), using tumor area positivity (PD-L1) and immune cell scoring (TIGIT). No hypothesis testing was predefined (p-value for descriptive purposes only). Descriptive comparisons were conducted for Arm A vs C, B vs C, and A vs B. Results: As of July 26, 2023, 126 patients (median age, 61.5 years) were randomized to Arm A (n=41), Arm B (n=42), or Arm C (n=43). Median follow-up: ~18 months (all arms). There was a trend of improvement in median PFS in Arm A (12.6 months) and Arm B (13.2 months) vs Arm C (9.5 months); HR (95% CI): Arm A vs C, 0.84 (0.46-1.52; p=0.2793); Arm B vs C, 0.80 (0.45-1.44; p=0.2414). ORR was 85.4% (3 CR) in Arm A, 88.1% (4 CR) in Arm B, and 76.7% (1 CR) in Arm C. Median DoR was 10.1 months in Arm A, 11.5 months in Arm B, and 8.2 months in Arm C. Median OS was not reached in any arm. Analyses showed that PD-L1 or TIGIT expression did not correlate with efficacy, however, small subgroup size limits interpretability. All patients experienced ≥1 treatment-related adverse event (TRAE); rates of grade ≥3 TRAEs were 73.2%, 78.6% and, 65.1% in Arms A, B, and C, respectively. The most common TRAEs included anemia (80.5% in Arm A vs 83.3% in Arm B vs 81.4% in Arm C), nausea (80.5% vs 76.2% vs 65.1%), and WBC count decreased (78.0% vs 76.2% vs 62.8%). Rates of TRAEs leading to any treatment discontinuation were 26.8%, 21.4%, and 4.7% in Arms A, B, and C, respectively. One patient in each arm experienced a TRAE leading to death. Conclusion: In patients with untreated limited-stage SCLC, tislelizumab + cCRT yielded a trend of improvement in PFS and ORR vs cCRT; addition of ociperlimab did not show detectable improvement. The overall safety profile of the treatments was tolerable, manageable, and generally consistent with the known risks of ociperlimab, tislelizumab, and cCRT. Citation Format: Youling Gong, Qingsong Pang, Rong Yu, Zhengfei Zhu, Jiangqiong Huang, Yufeng Cheng, Diansheng Zhong, Hongbo Wu, Seung Soo Yoo, Tracy Dobbs, Zinan Bao, Yunxia Zuo, Boxian Wei, Pu Sun, You Lu. AdvanTIG-204: A phase 2, multicenter, randomized, 3-arm, open-label study investigating the preliminary efficacy and safety of ociperlimab (anti-TIGIT) + tislelizumab (anti-PD-1) + concurrent chemoradiotherapy (cCRT) in patients with untreated limited-stage small cell lung cancer (SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT255.

Analysis of Risk Factors for Febrile Neutropenia in Patients with Small-Cell Lung Cancer Receiving Carboplatin Plus Etoposide Therapy

Introduction: Febrile neutropenia (FN) is an oncologic emergency requiring immediate empiric antibiotic therapy. Although carboplatin plus etoposide combination chemotherapy is associated with a relatively high frequency of FN, the risk factors are unclear. Hence, this retrospective study aimed to identify predictive markers of carboplatin/etoposide-induced FN. Methods: We conducted a retrospective cohort analysis of patients with previously untreated small-cell lung cancer (SCLC) who received combination chemotherapy with carboplatin (area under the concentration curve: 5 mg/mL·min, day 1) and etoposide (80 or 100 mg/m2, days 1–3) between July 2007 and June 2022. FN was assessed during the 21 days after initiation of carboplatin and etoposide therapy according to the Japanese Society of Medical Oncology’s definition. Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables were used to compare the two groups. Statistical significance was set at p values <0.05. Explanatory variables with p values <0.05 in the univariate analysis were included in the multivariate logistic regression analysis. Results: Among the 176 eligible patients, the incidence of FN during the first cycle of chemotherapy was 25.0% (44/176). Multivariate analysis revealed that co-administration of proton pump inhibitors (PPIs) or potassium-competitive acid blockers (PCABs) and body mass index (BMI) were significantly associated with FN (p = 0.0035 and 0.0011, respectively). Patients with both co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 presented with significantly higher frequencies of FN compared with the other patients (13/24 [54.2%] vs. 31/152 [20.4%] patients; odds ratio: 4.56, 95% confidence interval: 1.70–12.48; p = 0.00147). Conclusion: Patients who received carboplatin plus etoposide for SCLC with co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 more frequently present with FN than those without the two factors.

Outcomes and Prognostic Factors of Extensive Stage Small Cell Lung Cancer: A Retrospective Study

Introduction Small cell lung cancer (SCLC) represents about 15% of all lung cancers. Extensive stage (ES) SCLC represents around 60% of diagnosed SCLC cancers. The median survival in untreated ES SCLC is 2 to 4 months and that of treated cases is 8 to 13 months. Aim and Objectives This retrospective analysis aims to find out the clinical outcome of patients with ES SCLC and the prognostic factors affecting their survival. Methods Details of patients registered in the department of radiation oncology from January 1, 2010 to September 30, 2019 were retrieved from the hospital records. This includes the demographic characteristics, treatment received, toxicity, and follow-up details. Results Two-hundred eighty-three patients were included. Median age of presentation was 62 years. Around 97.5% of patients were men. Smokers constitute 94% of all cases. About 86.9% (246 patients) of cases were not alive at the end of the study period. The median estimated overall survival (OS) was 7 months ± 0.47 (95% confidence interval [CI]: 6.026–7.974) and progression-free survival (PFS) was 5 months ± 0.535 (95% CI: 3.952–6.048). Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), hyponatremia, number of chemotherapy cycles, consolidative radiotherapy (RT) and prophylactic cranial irradiation (PCI) were found to have prognostic effect on OS. Smoking, ECOG PS, number of chemotherapy cycles, consolidative RT, and PCI were found to have prognostic effects on PFS. Conclusion There is a difference in OS and PFS patterns of ES SCLC patients among various Indian studies even though the available data is scarce. Our study shows that the OS and PFS of our study population are comparable to other South Indian studies available. PS, serum sodium level, number of chemotherapy cycles, consolidative RT, and PCI were found to be independent prognostic factors for survival of ES SCLC. The identification of these factors will help physicians to tailor treatment.

Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer

Programmed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC. To evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC. This international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021. Patients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks. The primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P < .012). There were 13 secondary outcomes, including progression-free survival and adverse events. Among the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P < .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group. Among patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population. ClinicalTrials.gov Identifier: NCT04063163.

Phase I study of entinostat (Ent), atezolizumab (A), carboplatin (C), and etoposide (E) in previously untreated extensive-stage small cell lung cancer (ES-SCLC), ETCTN 10399.

e20606 Background: A-CE has demonstrated improved overall survival in ES-SCLC, but there are currently no approved therapies targeting genomic alterations in SCLC. Mutations in acetyltransferases CREBBP and EP300 occur at a frequency of 15% and 13%, respectively, in SCLC, and PDX models with CREBBP mutations were demonstrated to be susceptible to targeting with HDAC inhibitors. Ent, a class I selective HDAC inhibitor, has also demonstrated clinical activity in a combination with pembrolizumab in patients with NSCLC and uveal melanoma with minimal hematologic toxicity at RP2D of 5 mg PO weekly. We conducted a phase I trial to evaluate the combination of Ent with A-CE for ES-SCLC, NCI ETCTN 10399. Methods: Patients (pts) with treatment-naïve ES-SCLC, stable or treated brain metastases, ECOG ≤2 were enrolled and treated on up to 4 dose levels of Ent. Allocation to cohorts was determined using Bayesian optimal interval (BOIN) design targeting a MTD with a DLT rate of 20%. Dose levels (DL) included Ent 2 mg, 3 mg, or 5 mg PO weekly on day (d) 1 in addition to 4 cycles of A-CE (A 1200 mg, C AUC 5, E 100 mg/m2 d 1-3) followed E+A for 1 year. Pre-treatment tissue and plasma collected for WES. Results: 3 pts were enrolled and treated at DL1 with Ent 2 mg. Pts were age 69-83, 2 male, 1 female, 2 were ECOG 1, 1 was ECOG 0, and 1 with prior SRS radiation for brain metastases. 2 of 3 experienced DLTs during cycle 1: (1) Grade (Gr) 4 febrile neutropenia after 2 doses of Ent and (1) Gr 5 sepsis after 1 dose of Ent. BOIN design required stopping accrual to dose level 1 and the trial was closed to further accrual. The pt without DLT experienced grade 3 thrombocytopenia after 2 doses of Ent, but recovered after holding cycle 1, day 15 Ent. This patient experienced Gr 3 neutropenia during cycle 2. The most common adverse events were anemia (3), neutropenia (3), thrombocytopenia (2), leukopenia (2), hypocalcemia (2). Of these, most were Gr 3-4: anemia (1), neutropenia (3), thrombocytopenia (2), leukopenia (1), hypocalcemia (1). Conclusions: The combination of low dose Ent 2 mg PO weekly + AC-E is unsafe and resulted in early onset and severe neutropenia, thrombocytopenia in the first 1-2 weeks and ≥Gr 3 neutropenia and thrombocytopenia prior to completing 2 cycles of treatment for all pts. There is no role for further exploration of entinostat with carboplatin, etoposide, and atezolizumab. Clinical trial information: NCT04631029.

Rationale and Design of the Phase 3 KEYLYNK-013 Study of Pembrolizumab With Concurrent Chemoradiotherapy Followed by Pembrolizumab With or Without Olaparib for Limited-Stage Small-Cell Lung Cancer

BackgroundThe current standard of care for patients with newly diagnosed limited-stage small-cell lung cancer (SCLC) is concurrent chemoradiotherapy (CCRT). The prognosis remains poor due to the aggressiveness and high risk of progression or relapse of SCLC even if an initial response is achieved. Therefore, there is an urgent unmet clinical need in this population. The multicenter, phase 3, randomized, placebo-controlled, double-blind KEYLYNK-013 study evaluates the addition of pembrolizumab to CCRT followed by pembrolizumab with or without olaparib in participants with previously untreated limited-stage SCLC. (ClinicalTrials.gov: NCT04624204). MethodsEligible participants aged ≥18 years with newly diagnosed, pathologically confirmed, limited-stage (ie, stage I-III) SCLC will be randomized 1:1:1 to CCRT (ie, etoposide plus carboplatin or cisplatin for 4 cycles and standard thoracic radiotherapy) plus pembrolizumab (Groups A and B) or CCRT plus placebo (Group C). In the absence of disease progression, participants will receive pembrolizumab plus placebo (Group A), pembrolizumab plus olaparib (Group B), or placebo (Group C). Dual primary endpoints are progression-free survival per RECIST version 1.1 by blinded independent central review and overall survival. ResultsEnrollment began in December 2020 and is ongoing at approximately 150 sites. ConclusionsKEYLYNK-013 will provide valuable information on the efficacy and safety of pembrolizumab plus CCRT and pembrolizumab with or without olaparib post CCRT in participants with limited-stage SCLC.

Treatment and Prevention of Brain Metastases in Small Cell Lung Cancer.

Central nervous system (CNS) metastasis will develop in 50% of small cell lung cancer (SCLC) patients throughout disease course. Development of CNS metastasis poses a particular treatment dilemma due to the accompanied cognitive changes, poor permeability of the blood-brain barrier to systemic therapy and relatively advanced state of disease. Survival of patients with untreated SCLC brain metastases is generally <3 months with whole brain radiotherapy used as first-line management in most SCLC patients. To prevent development of CNS metastasis prophylactic cranial irradiation (PCI) is recommended in limited stage disease, after response to chemotherapy and radiation, while PCI may be considered in extensive stage disease after favorable response to upfront treatment. Neurocognitive toxicity with whole brain radiotherapy and PCI is a concern and remains difficult to predict. The mechanism of toxicity is likely multifactorial, but a potential mechanism of injury to the hippocampus has led to hippocampal sparing radiation techniques. Treatment of established non-small cell lung cancer CNS metastases has increasingly focused on using stereotactic radiotherapy (SRS) and it is tempting to extrapolate these results to SCLC. In this review, we explore the evidence surrounding the prediction, prevention, detection, and treatment of CNS metastases in SCLC. We further review whether existing evidence supports extrapolating less toxic treatments to SCLC patients with CNS metastases and discuss trials that may shed more light on this question.

Imfirst: A phase IIIb, safety, single arm study of carboplatin (CB) or cisplatin (CP) plus etoposide (ET) with atezolizumab (ATZ) in patients with untreated extensive-stage small cell lung cancer (ES-SCLC) in Spain—Primary safety results of the induction phase.

8567 Background: Clinical trial (CT) IMpower133 met both primary endpoints and is the first CT to show significant clinical improvement over standard chemotherapy (C) with a good safety profile in first line (1L) ES-SCLC. The addition of ATZ to CB + ET resulted in an OS landmark of 34% and 22% compared to 21% and 16.8% of patients alive at 18 and 24 months respectively versus C. IMfirst evaluates ATZ + CB or CP + ET in a broader patient population than the pivotal study. ECOG Performance status (PS) 2, asymptomatic untreated brain metastases, underlying stable autoimmune diseases and HIV+ pts are eligible. IMfirst also includes the possibility of 6 C induction cycles according to investigator´s choice and consolidation radiotherapy. Methods: To evaluate the safety and efficacy of ATZ added to CB or CP + ET as 1L treatment in an interventional real world setting of ES-SCLC. Exploratory endpoints include tumor biomarker analysis related to ATZ. Results: As of Oct 2020, 117 pts had been enrolled, 105 treated with ATZ + CB + ET and 12 with ATZ + CP + ET. The median age was 65 years (Y) (range 35-89); 84 males; 14 pts (12%) had CNS metastases and 66 pts were current smokers and 50 former smokers, one had never smoked. The PS was 0 in 28 pts (24%), 1 in 75 (64%) and 2 in 14 (12%). The median of cycles of ATZ received was 4 for all the pts (range 1-12) and 2 for the pts (40) in maintenance phase (range 1-8). Number of pts with adverse events (AEs) was 109, 36 with Serious Adverse Events (SAEs) and 63 with AEs. 8 pts had SAEs related to treatment, 4 had adverse events of special interest and 13 pts discontinued the treatment due to AEs: 6 to ATZ, 12 to CB or CP and 10 to ET, 1 patient discontinued ATZ due to a related AE. Table shows the treatment related AEs (TRAEs). No grade 5 TRAEs were reported. Conclusions: IMfirst induction phase analysis confirms the safety profile of ATZ plus C in a broader population of patients. Efficacy, biomarker and further safety analyses will be presented in the future with longer follow up.[Table: see text]

Quel rôle pour l’irradiation cérébrale prophylactique dans le cancer à petites cellules ? Une étude rétrospective unicentrique

Prophylactic cranial irradiation (PCI) is considered standard therapeutic management in small cell lung cancer (SCLC). This is based on old randomised trials with methodological limitations, namely the absence of magnetic resonance imaging (MRI) of the brain. The aim of this study is to assess the risk not administering PCI when systematic brain imaging is applied. Retrospective study including untreated SCLC, without PCI and receiving brain imaging at the time of diagnosis. Kaplan-Meier and log-rank statistics were used for survival analyses. Among 150 patients, 75 were possibly eligible for PCI. Thirteen patients presented with an isolated brain recurrence as the first site of progression with no other metastatic sites apparent, and in 6 patients, the brain was the only recurrent site during the whole follow-up. In the group of patients eligible for PCI, there was no statistically significant survival difference according to the brain progression status (P=0.11). The expected impact of PCI seems limited in terms of overall survival and prevention of isolated brain metastases in patients having systematic brain imaging during SCLC work-up.

Evaluation of diagnostic and predictive values of the serum VEGF-A level and systemic immune-inflammation index in small cell lung cancer.

Purpose: To evaluate diagnostic and predictive values of the serum vascular endothelial growth factor-A (VEGF-A) level and systemic immune-inflammation index (SII) in small cell lung cancer (SCLC) patients.Methods: From January 2018 to April 2020, we prospectively enrolled 59 untreated SCLC patients in the study group and 50 non-neoplastic patients in the control group. Blood samples were collected at baseline, after the first two cycles of chemotherapy and at progression in the study group and at entry in the control group. Serum VEGF-A was measured by chemiluminescence, SII was calculated based on complete blood count results, and the relationship between the VEGF-A/SII and clinicopathological characteristics, chemotherapeutic efficacy and progression-free survival (PFS) of SCLC patients was analyzed.Results: Baseline serum VEGF-A was significantly higher in SCLC patients than in non-neoplastic patients (P<0.001), while baseline SII was not (P=0.114). There was no correlation between baseline VEGF-A and SII in SCLC patients (P=0.123); however, there was a significant correlation between baseline VEGF-A and disease stage and central nervous system (CNS) metastasis (P=0.021 and P=0.012, respectively), as well as between baseline SII and disease stage and liver metastasis (P=0.026 and P=0.018, respectively). Serum VEGF-A was significantly lower than the pretreatment level after 2 cycles of treatment (P=0.049) but was not different at progression (P=0.247). Baseline VEGF-A was correlated with the treatment response of first-line chemotherapy (P=0.001), while baseline SII was not (P=0.392). Kaplan-Meier survival analysis suggested that the PFS of first-line chemotherapy was significantly longer in the low-VEGF-A group at baseline than the high-VEGF-A group (11.37 vs. 6.17 months, P<0.001). There was a trend toward longer PFS of first-line chemotherapy in the low-SII group at baseline than the high-SII group, but the difference was not significant (12.10 vs. 9.10 months, P>0.050). Univariate and multivariate Cox regression analyses suggested that baseline VEGF-A (HR: 3.443, 95% CI: 1.330-8.908, P=0.011) was an independent prognostic factor for PFS in SCLC patients.Conclusions: Baseline serum VEGF-A and SII are associated with important clinicopathological characteristics of SCLC patients. VEGF-A, but not SII, has the ability of diagnosis and predicting first-line chemotherapeutic efficacy and prognosis in SCLC patients.

Efficacy and Safety of First-Line Immunotherapy in Combination with Chemotherapy for Patients with Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis.

Background The prognosis of patients with extensive-stage small cell lung cancer (SCLC) is poor. Adding an immune checkpoint inhibitor (ICI) to chemotherapy may exert a synergistic effect and improve survival outcomes. However, for treatment-naive extensive-stage SCLC patients, the efficacy of immunotherapy in combination with cytotoxic chemotherapy remains controversial. Objective To evaluate the benefits and risks of the combination of immunotherapy and chemotherapy and to assess the comparative effectiveness of different first-line treatment strategies for extensive-stage SCLC. Methods PubMed, Web of Science, EMBASE, and Cochrane Library were searched for randomized clinical trials studying different immunotherapeutics for patients with previously untreated extensive-stage SCLC up to Feb 16, 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events. Results We identified 141 published records, and 4 studies (comprising 2202 patients) were included in the analysis. Immunotherapy (including ipilimumab, atezolizumab, and durvalumab) plus chemotherapy was associated with better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75–0.93; risk ratio (RR) 0.90, 95% CI 0.81–1.00) and PFS (HR: 0.81, 95% CI 0.74–0.88; RR 0.96, 95% CI 0.93–0.99) than placebo plus chemotherapy. The addition of immunotherapy to chemotherapy showed similar improvement in ORR, DCR, and adverse events versus placebo plus chemotherapy. On the surface under the cumulative ranking (SUCRA) analysis, the anti-PD-L1 agent, atezolizumab, had the highest likelihood of achieving improved OS (93.4%) and PFS (95.0%). Conclusion In the first-line setting, combining immunotherapy with chemotherapy is better than standard chemotherapy in terms of OS and PFS. Across the eligible studies, PD-L1 inhibitors might be preferred. Further explorations of more ICIs in the first-line treatment for extensive-stage SCLC patients should be needed.

A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer

A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer

First-line atezolizumab plus chemotherapy in treatment of extensive small cell lung cancer: a cost-effectiveness analysis from China.

IMpower 133 trial first confirmed the efficacy and safety of adding atezolizumab or placebo to first-line treatment with chemotherapy in patients with extensive-stage small-cell lung cancer (SCLC). While, overprice limited its broad use in clinical. The aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China. A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients. Utility values were obtained from published studies, and the costs were acquired from real world and literature. Additionally, sensitivity analyses based on a willingness-to-pay (WTP) threshold were performed to identify the uncertain parameters of Markov model. Total costs of atezolizumab group were $48,129, while cost of chemotherapy alone was just $12,920 in placebo group. The quality-adjusted life-years (QALYs) in atezolizumab group was just 0.072 higher than that in placebo group (0.858 QALYs vs. 0.786 QALYs). The cost-effectiveness ratio between atezolizumab combination with chemotherapy and chemotherapy alone was $489,013/QALY in China. The net benefit of placebo group was significantly higher than atezolizumab group. One-way sensitivity analyses highlighted that utilities of the progression-free survival (PFS) and progression disease state in placebo group were the most influential parameter. Atezolizumab combination therapy was not more cost-effective than chemotherapy alone at a WTP threshold of $25,929/QALY in China.

A Study of Atezolizumab in Combination With Carboplatin Plus Etoposide to Investigate Safety and Efficacy in Patients With Untreated Extensive-Stage Small Cell Lung Cancer

A Study of Atezolizumab in Combination With Carboplatin Plus Etoposide to Investigate Safety and Efficacy in Patients With Untreated Extensive-Stage Small Cell Lung Cancer

Cost-effectiveness analysis of atezolizumab plus chemotherapy in the first-line treatment of extensive small cell lung cancer in China.

e20083 Background: Atezolizumab plus chemotherapy as a first-line therapy has shown significant survival benefits in patients with extensive small-cell lung cancer (SCLC). While, overprice limited its broad use in clinical. Here, the aim of this study was to evaluate the cost-effectiveness of atezolizumab plus chemotherapy in treatment of extensive SCLC as first line in China. Methods: A Markov model was established by extracting data from the IMpower 133 trial with untreated extensive SCLC patients. Utility values were obtained from published studies, and the costs were acquired from real world and literature. Additionally, sensitivity analyses based on a willingness-to-pay threshold (WTP) were performed to identify the uncertain parameters of Markov model. Results: Total costs of atezolizumab group was $183801, while cost of chemotherapy alone group was just $12920 in placebo group. The QLAYs in atezolizumab group was just 1.15 higher than that in placebo group (13.73 QALYs vs. 12.58 QALYs). The ICER between atezolizumab combination with chemotherapy and chemotherapy alone was $148592/QALY in China. The net benefit of placebo group was significantly higher than atezolizumab group. One-way sensitivity analyses highlighted that utilities of the PFS and PD state in placebo group were the most influential parameter. Conclusions: Atezolizumab combination therapy was not more cost-effective than chemotherapy alone therapy at a WTP threshold of $25929/QALYs in China.

Randomized controlled trial of lobaplatin plus etoposide vs. cisplatin plus etoposide as first-line therapy in patients with extensive-stage small cell lung cancer.

The majority of previous studies of lobaplatin in small cell lung cancer (SCLC) are small phase I-II studies. The present study aimed to verify the non-inferiority (in terms of efficacy) of lobaplatin plus etoposide (EL) vs. cisplatin plus etoposide (EP) in patients with previously untreated extensive-stage SCLC (ES-SCLC). This phase III non-inferiority randomized clinical trial enrolled patients at 17 sites between September 2010 and May 2013. Patients were randomized to EL (30 mg/m2 lobaplatin on day 1 and 100 mg/m2 etoposide on days 1-3, for 21-day cycles) or EP (80 mg/m2 cisplatin on day 1 and 100 mg/m2 etoposide on days 1-3, for 21-day cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, disease control rate (DCR), toxicity and quality of life (QoL). A total of 234 patients were randomized to the EL (n=122) and EP (n=112) treatment groups. The median PFS, median OS and DCR were 5.1 vs. 5.3 months (P=0.786), 10.6 vs. 9.7 months (P=0.701) and 85.5 vs. 86.7% (P=0.848) in the EL vs. EP groups, respectively. Patients in the EL group had significantly lower frequencies of nephrotoxicity (2.5 vs. 11.7%; P=0.008), nausea (22.3 vs. 40.5%; P=0.003) and vomiting (14.1 vs. 35.1%; P<0.001) than those in the EP group. Overall, EL was not inferior to EP in terms of PFS and OS. The tolerance and QoL of the EL regimen were better than those of the EP regimen. EL is thus an alternative choice for the first-line treatment of ES-SCLC.

Irinotecan-platinum combination therapy for previously untreated extensive-stage small cell lung cancer patients: a meta-analysis

BackgroundThere is still a debate regarding whether regimens combining irinotecan with platinum could replace regimens combining etoposide with platinum, as first-line chemotherapy for extensive-stage small cell lung cancer (ES-SCLC). We performed a meta-analysis to compare these regimens as first-line chemotherapy for ES-SCLC.MethodsA literature search for randomized controlled trials was performed using the Cochrane Library, PubMed, and Embase. The inverse variance method was used to estimate summary hazard ratios and their 95% confidence intervals for overall survival and progression free survival. Relative risk was used to estimate the overall response rate, disease control rate, 1-year survival, 2-year survival, and adverse event data.ResultNine randomized controlled trials (2451 patients) were included. Regimens combining irinotecan and platinum improved overall survival, progression-free survival and overall response rate compared to combination etoposide and platinum regimens. Meanwhile, superior progression-free survival and overall response rate outcomes were observed in the Asian subgroup of patients. These patients receiving a combination irinotecan and platinum regimen experienced grade 3–4 diarrhea more frequently and experienced less hematologic toxic events than the non-Asian groups.ConclusionsOur data suggest that a combination irinotecan and platinum regimen can prolong overall survival, progression-free survival and overall response rate for patients with ES-SCLC as compared to a combination etoposide and platinum regimen. And the Asian patients could benefit from irinotecan combined with platinum easier.

Advances in antibody therapeutics targeting small-cell lung cancer.

The proportion of small-cell lung cancer (SCLC) among all lung cancers decreased from 17.26% in 1986 to 12.95% in 2002. Chemotherapy is the key mode of treatment. However, novel therapeutic strategies and drugs are imperative, as the prognosis remains poor. In recent years, antibody therapies have shown promising prospects against malignancy. This review focuses on the advances in antibody therapies in SCLC. Although the results of pembrolizumab, nivolumab, ipilimumab, and rovalpituzumab tesirine are inspiring, all of the clinical trials on these drugs are phase I/II and have been verified for further phase III clinical trials. It was demonstrated that chemotherapy in combination with bevacizumab can improve the progression-free survival (PFS) in phase III trials. The insulin-like growth factor-1 receptor (IGF-1R) is associated with a poor prognosis in SCLC, while the anti-IGF-1R monoclonal antibody figitumumab has a potential therapeutic value. Tarextumab, an antibody that blocks both Notch2 and Notch3 signaling, in combination with etoposide and platinum (EP) in patients with untreated extensive-stage SCLC, proved to be well-tolerated and showed dosedependent anti-tumor activity. The therapeutic effect of sacituzumab govitecan, BW-2 and lorvotuzumab mertansine in SCLC warranted further evaluation. Bec2/BCG as an adjuvant vaccination in patients with limited-disease SCLC could not improve the survival, PFS, or quality of life. Thus, clinical studies are essential to confirm the anti-tumor efficacy of trastuzumab in SCLC.

Outcomes and Prognostic Factors of Small Cell Lung Cancer: A Retrospective Study

Background: Small cell lung cancer (SCLC) is a high grade neuroendocrine tumor, and has aggressive nature, so the majority of cases are presented with extensive disease. SCLC was staged into 2 categories: limited-stage disease (LS-SCLC) and extensive disease (ES-SCLC). Despite SCLC is sensitive to ra-diotherapy and chemotherapy, SCLC has high tendency for rapid dissemina-tion to regional and distant sites. Median survival time ranged from 2 - 4 months in patients with untreated SCLC. Multiagent chemotherapy was the primary treatment for SCLC. Aim of the work: This retrospective study was conducted to evaluate and analyze clinical features, treatment outcome, sur-vival and prognostic factors affecting survival in patients with SCLC presented to Clinical Oncology and Nuclear Medicine department, Chest department and Medical oncology unit in Mansoura Oncology Centre during the period from 2000-2015. Methods: Data of patients were collected from their files. The information obtained included demographic features, treatment received; its toxicity and outcome, survival and its prognostic factors. Demographic data were: age, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), smoking status, stage of disease. Data also included disease presentation and metastatic sites. Several factors affecting survival were analysed as age, sex, stage, PS, smoking status and LDH. Results: Sixty-three patients were enrolled in this study. Median age was 56.2 ± 6. Strong male predominance (92.1%) was observed; 84.1% of them were smoker. Thirty six patients (57.2%) were of ECOG-PS of 0 - 1. ES-SCLC was reported in 65% of cases and LDH was high (>1.5 xN) in 47.6%. The most common symptom was chest pain (38.1%) followed by cough (31.8%), weight loss (30%). Fifteen patients had single metastatic site (23.8%) and bone was the most common site of metastasis (reported in 8 patients) followed by brain, lung and liver. 2-year overall survival rate was 35% with median survival time of 14 months. On multivariate analysis, there were significantly higher survival in patients aged < 65 years (P = 0.03), female gender (P = 0.04), LD-SCLC (P = 0.03), good performance status (P = 0.04), low LDH level (P = 0.02) and non-smoker (P = 0.04). Conclusion: This clinico-epidemiologic study provides multiple prognostic factors that have important impact on survival as age, sex, LDH level, stage, smoking and performance status. Larger number of patients and prospective studies are needed to clarify more prognostic factor.

Irinotecan compared with etoposide in combination with platinum in previously untreated extensive stage small cell lung cancer: An updated systemic review

Irinotecan compared with etoposide in combination with platinum in previously untreated extensive stage small cell lung cancer: An updated systemic review