EvaluatioN of durvALumab Utilization and Effectiveness for First Line Extensive Stage Small Cell Lung Cancer. Prospective Cohort of Extensive Stage Small Cell Lung Cancer Patients Treated With Durvalumab Associated With Platinum-etoposide Chemotherapy
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 254
- 试验地点
- 34
- 主要终点
- The time to first line treatment discontinuation (TTD).
研究概览
简要总结
Small cell lung cancer (SCLC), characterized by rapid proliferation, high growth fraction and early development of metastases, is the most aggressive form of lung cancer. In 2021, an estimated 2.3 million people around the world are diagnosed with lung cancer. In France, in 2018, with 46 363 new cases and 33 117 deaths, lung cancer represented the second most common cancer and the first cause of death from cancer. Among those, SCLC represented 10,8% of all new lung diagnosis, and about two thirds presented at the extensive stage (ES-SCLC).
Since last three decades, standard treatment in ES-SCLC is based on combination chemotherapy with a platinum agent and etoposide in first-line with or without concurrent radiation therapy. Then, the second-line of treatment is topotecan, with few results in terms of response rates and survival rate. However, the emergence of immune checkpoint inhibitors targeting the programmed cell death receptor-1 (PD-1)/PD-ligand 1 (PD-L1) pathway, having an important role in immune regulation became an alternative method in the management and care of disease. Indeed, recent studies have shown an overall survival (OS) benefit for patients with ES-SCLC treated in first line with a combination of platinum-etoposide and immune checkpoint inhibitors. Atezolizumab (Tecentriq®, Roche) and durvalumab (Imfinzi®, AstraZeneca), two anti-Programmed death-ligand 1 (PD-L1) antibodies, delivered positive phase III results, respectively through the Impower-133 and CASPIAN studies, and were granted European market authorisations.
Durvalumab is approved for use in combination with etoposide and either carboplatin or cisplatin for the first-line treatment of patients with ES-SCLC. On March 10, 2020 French health authorities allowed durvalumab utilization in this setting through a national "early access program" (Autorisation Temporaire d'Utilisation "de cohorte" - ATUc), thus preceding the European market authorization (August 28, 2020). Since 2020 October 1st, durvalumab is used as a post ATU treatment. Since 2020, French AURA treatment guidelines for SCLC have referenced durvalumab in combination with chemotherapy as a first-line treatment option for patients with ES-SCLC.
Whereas the safety and efficacy of the durvalumab have been evaluated in a clinical trial, data are required to further evaluate the use of durvalumab in real-life condition and in less selected population than in clinical trials.
详细描述
Small cell lung cancer (SCLC), characterized by rapid proliferation, high growth fraction and early development of metastases, is the most aggressive form of lung cancer. SCLC is a relatively rare but really aggressive tumour accounting for 10-15% of all newly diagnosed lung cancer. In 2021, an estimated 2.3 million people around the world are diagnosed with lung cancer . In France, in 2018, with 46 363 new cases and 33 117 deaths, lung cancer represented the second most common cancer and the first cause of death from cancer. Among those, SCLC represented 10,8% of all new lung diagnosis, and about two thirds presented at the extensive stage (ES-SCLC).
Between 2010 and 2018, the incidence rate increased of 0,3 % per year in men. In contrast, from 1990 to 2018, the incidence increased more dramatically among women, with an increase of 5% in average per year. The 5-year survival rate for all people with all types of lung cancer is 21%. The 5-year survival rate is 17% and 24% for men and women, respectively. For SCLC, due to the rapid proliferation and high growth fraction associated to early development of metastases in the disease course (most commonly to the brain, liver, or bone), the 5-year survival rate is low at 10%. Therefore, SCLC is the most lethal lung cancer subtype. Most cases of SCLC develop in patients aged 60-80 years and the estimated overall death rate is 25,000-30,000 per year in United States. More than 90% of patients with SCLC are elderly and have heavy smoking histories.
SCLC is defined histologically as "a malignant epithelial tumour consisting of small cells with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin, and absent or inconspicuous nucleoli", assessed by imaging techniques such as computerized tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI).
The Veterans' Administration Lung Study Group (VALG) staging system is usually used in the clinic routine to stage SCLC. Two categories represent SCLC, limited stage (LS) and extensive stage (ES). Limited-stage small-cell lung cancer (LS-SCLC) is defined as tumour confined to one hemithorax, with or without regional lymph-node involvement, which can be safely encompassed in a tolerable radiation field, corresponding at stage I to III of TNM system. ES-SCLC is defined as disease that cannot be safely encompassed in a tolerable radiation field, corresponding to stage IV of TNM system.
The management of SCLC is complicated by aggressiveness and substantial comorbidities, and impaired performance status. According to ESMO guidelines (2021), as well as in the French guidelines from Auvergne Rhone Alpes region, the standard management design of SCLC is described and outlined in Figure 1.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (at least 18 years of age at time of treatment decision),
- •Patients with histologically or cytologically proven SCLC and extensive disease according to the Veterans Administration Lung Study Group (VALSG) classification or TNM staging (Brierley et al, 2017) before durvalumab + platinum-etoposide treatment*,
- •Patients newly treated in first line with durvalumab + platinum-etoposide**,
- •Patients informed and not opposed to participating in the study.
排除标准
- •Patients with contraindications to receiving durvalumab + platinum-etoposide,
- •Patients participating in another interventional clinical trial for first line ES-SCLC.
结局指标
主要结局
The time to first line treatment discontinuation (TTD).
时间窗: TTD is defined as the time from the index date to the date of last durvalumab infusion (+3 weeks during induction period and +4 weeks during maintenance period) or date of death (up to 36 months)).
For patients who start durvalumab at a later cycle than first cycle PE, the index date will be the first infusion of PE. If the treatment is stopped during the first phase of 4 to 6 cycles (induction) with a new re- start of durvalumab and PE, the treatment will be considered as temporary stop. If the treatment is stopped during the durvalumab maintenance with a re-start of durvalumab in monotherapy, the treatment will be also considered as temporary stop. Durvalumab will be considered definitely discontinued when the maintenance phase with durvalumab in monotherapy is stopped and results in a new administration of PE (+/-durvalumab) (subsequent treatment line). For patients still receiving durvalumab at the end of follow-up or when they are lost to follow-up, TTD will be right-censored at the last recorded day of ongoing durvalumab treatment.
次要结局
- Safety profile of durvalumab + chemotherapy (PE) (treatment-related AE).(At the end of follow-up (up to 36 months).)
- Disease control rate (DCR)(At the end of follow-up (up to 36 months))
- Time to second real-world progression (rwPFS2)(rwPFS2 (up to 36 months))
- Sociodemographics characteristics at durvalumab + platinum-etoposide initiation(At baseline)
- Describe patient history prior to durvalumab initiation(Before durvalumab discontinuation)
- Describe the safety profile of durvalumab + chemotherapy (PE) (treatment-related AE).(At the end of follow-up (up to 36 months).)
- Clinical characteristics at durvalumab + platinum-etoposide initiation(At baseline)
- Real-world Overall Survival (rwOS)(rwOS rate at 1, 2 and 3 years (rwOS1y, rwOS2y, rwOS3y))
- Real world Progression Free Survival (rwPFS)(rwPFS rate at 6, 12, 18, 24 and 36 months (rwPFS6m, rwPFS12m, rwPF18m, rwPFS24m, rwPFS36m) up to 36 months.)
- Patient individual best response(From the start of treatment until disease progression (up to 36 months)..)
- Overall response rate (ORR)(From the start of treatment until disease progression (up to 36 months).)
- Real-world Overall Survival (rwOS)(rwOS rate at 1, 2 and 3 years (rwOS1y, rwOS2y, rwOS3y))
- Real world Progression Free Survival (rwPFS)(rwPFS rate at 6, 12, 18, 24 and 36 months (rwPFS6m, rwPFS12m, rwPF18m, rwPFS24m, rwPFS36m) up to 36 months.)
- Patient individual best response(From the start of treatment until disease progression (up to 36 months)..)
- Time to second real-world progression (rwPFS2)(rwPFS2 (up to 36 months))
- Sociodemographics characteristics at durvalumab + platinum-etoposide initiation(At baseline)
- Overall response rate (ORR)(From the start of treatment until disease progression (up to 36 months).)
- Describe patient history prior to durvalumab initiation(Before durvalumab discontinuation)
- Describe the safety profile of durvalumab + chemotherapy (PE) (treatment-related AE).(At the end of follow-up (up to 36 months).)
- Clinical characteristics at durvalumab + platinum-etoposide initiation(At baseline)
- Safety profile of durvalumab + chemotherapy (PE) (treatment-related AE).(At the end of follow-up (up to 36 months).)
- Disease control rate (DCR)(At the end of follow-up (up to 36 months))
- Describe patient history prior to durvalumab initiation(Before durvalumab initiation)