An Ambispective, Non-interventional, Multiple Cohort Study to Assess the Management of Osimertinib Treatment in Patients With EGFRm Non-small Cell Lung Cancer Under Real-world Conditions in Spain
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 500
- 试验地点
- 27
- 主要终点
- To evaluate the effectiveness of osimertinib in terms of median OS in patients with locally advanced or metastatic EGFRm NSCLC (Cohort 1).
研究概览
简要总结
Lung cancer (LC) is the tumor responsible for the highest mortality worldwide. Lung adenocarcinoma is the major subtype of lung cancer and represents the deadliest human cancer, affecting current-, ex-, and even non-smokers.
Osimertinib is indicated as monotherapy for the first-line (1L) treatment of adult patients with locally advanced or metastatic NSCLC with activating mutations in the EGFR, for the treatment of adult patients with EGFR T790M mutation-positive locally advanced or metastatic NSCLC, for the adjuvant treatment of adult patients with NSCLC stages IB-IIIA after complete resection of the tumor that has activating mutations of the EGFR, for the treatment of adult patients with locally advanced, unresectable NSCLC whose tumours have EGFR exon 19 deletions or exon 21 substitution mutation and whose disease has not progressed during or following platinum-based chemoradiation therapy, and in combination with pemetrexed and platinum-based chemotherapy for the 1L treatment of adult patients with advanced NSCLC whose tumours have EGFR exon 19 deletions or exon 21 substitution mutations.
The FLAURA trial showed that treatment with osimertinib significantly prolongs PFS and improves overall survival (OS) compared to standard EGFR tyrosine kinase inhibitors.
The results of the ADAURA study showed a reduction in the risk of recurrence or death by 83% in stages II to IIIA, and in 80% in stages IB-IIIA. Additionally, osimertinib demonstrated a highly statistically significant improvement in DFS and HRQoL was maintained.
The FLAURA2 trial showed that 1L treatment with osimertinib-chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR mutated (EGFRm) advanced NSCLC.
The LAURA trial showed that treatment with osimertinib after chemoradiotherapy resulted in significantly longer PFS than placebo among patients with unresectable stage III EGFRm NSCLC.
To date, there are no real-world data on osimertinib either in 1L treatment in locally advanced or metastatic EGFRm NSCLC nor as adjuvant treatment, in early stages of cancer, regarding effectiveness, adherence, treatment exposure and quality of life (QoL), among others, and in particular for the use of osimertinib in subpopulations less represented in pivotal trials such as elderly or patients with uncommon EGFR mutations. Furthermore, the duration of treatment in real life in Spain is also a gap, as it appears to be longer than in clinical trials, which means that there are patients who are treated beyond progression.
Therefore, this observational ambispective study based on real-world data aims to provide data on osimertinib use as adjuvant treatment in adult patients diagnosed with stages IB-IIIA EGFRm NSCLC, in 1L treatment in patients with locally advanced or metastatic EGFRm NSCLC, as consolidation treatment in patients with locally advanced, unresectable NSCLC whose tumours have EGFR exon 19 deletions or exon 21 substitution mutations and whose disease has not progressed during or following platinum-based chemoradiation therapy, and in combination with pemetrexed and platinum-based chemotherapy in patients with advanced NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution. Specifically, the study will focus on patient characteristics, adherence, treatment exposure, administration, survival, quality of life, effectiveness and safety providing insights into osimertinib use in daily practice for patients with EGFRm NSCLC, where there are current evidence gaps.
详细描述
Cancer continues to be one of the leading causes of morbidity and mortality in the world. It is estimated that in the year 2020, approximately 18.1 million new cases of cancer in the world, and that this figure will increase in the next two decades to 27 million. The most frequently diagnosed tumors in the world in 2020 were those of the breast, lung (which occupies the second position), colon and rectum, prostate and stomach, all of them with more than one million cases.
Also, in Spain, cancer is one of the main causes of morbidity and mortality. It is estimated that in 2020 there were 113,054 deaths from cancer in Spain. The number of cancers diagnosed in Spain in 2022 is estimated to reach 280,100 cases according to REDECAN calculations, which represents a slight increase compared to previous years. Lung cancer (LC) is the tumor responsible for the highest mortality worldwide. After prostate cancer, it is the second most common cancer in men and, after breast cancer, in women. Lung adenocarcinoma is the major subtype of lung cancer and represents the deadliest human cancer, affecting current-, ex-, and even non-smokers.
The most frequently diagnosed cancers in Spain in 2023 will be those of the colon and rectum, breast, lung, prostate, and urinary bladder. Lung cancer is a very common cancer in Spain, however, due to its high mortality, its prevalence at five years is relatively low.
Approximately 30% of patients with non-small cell lung cancer (NSCLC) have early-stage disease that is treated with surgery. A high percentage of these patients relapse and die, so patients receive postoperative adjuvant systemic chemotherapy to increase their survival. However, the benefits of this strategy are modest. NSCLC is often associated with druggable molecular alterations that drive lung carcinogenesis. EGFR tyrosine kinase inhibitors (TKIs) have been included in treatment paradigms with the aim of improving the outcome of adjuvant therapy in patients with completely resected, EGFR mutation-positive (EGFRm+) disease.
Osimertinib is indicated as monotherapy for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR), for the treatment of adult patients with EGFR T790M mutation-positive locally advanced or metastatic NSCLC, for the adjuvant treatment of adult patients with NSCLC stages IB-IIIA after complete resection of the tumor that has activating mutations of the EGFR (exon 19 deletion or exon 21 substitution (L858R)), for the treatment of adult patients with locally advanced, unresectable NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations and whose disease has not progressed during or following platinum-based chemoradiation therapy, and in combination with pemetrexed and platinum-based chemotherapy for the first-line treatment of adult patients with advanced NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female or male patients, treated with osimertinib
- •Age ≥ 18 years at starts of osimertinib treatment (i.e., index date).
- •Patients histologically diagnosed with EGFRm NSCLC (before index date):
- •Patients with first-line treatment with EGFRm locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy (Cohort 1).
- •Patients with stage IB-IIIA whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, after complete tumor resection (Cohort 2).
- •Patients with advanced NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, that received osimertinib in combination with pemetrexed and platinum-based chemotherapy for the first-line treatment (Cohort 3).
- •Patients with locally advanced, unresectable NSCLC treated with osimertinib, whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations and whose disease has not progressed during or following platinum-based chemoradiation therapy (cohort 4).
- •Provision of informed consent (for alive patients). Deceased patients who met the selection criteria when they started treatment with osimertinib could also be included in the study.
排除标准
- •Osimertinib treatment administration in a clinical trial setting.
研究组 & 干预措施
Cohort 1
Patients diagnosed with locally advanced or metastatic NSCLC with activating EGFR mutations that received first line treatment with osimertinib (FLAURA regimen).
Cohort 2
Patients with stage IB-IIIA NSCLC after complete tumour resection that has activating mutations in the EGFR (deletion of exon 19 or substitution of exon 21 [L858R]) that received adjuvant treatment with osimertinib (ADAURA regimen).
Cohort 4
Patients with locally advanced, unresectable NSCLC treated with osimertinib, whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations and whose disease has not progressed during or following platinum-based chemoradiation therapy (LAURA regimen).
Cohort 3
Patients with advanced NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, that received osimertinib in combination with pemetrexed and platinum-based chemotherapy for the first- line treatment (FLAURA2 regimen).
结局指标
主要结局
To evaluate the effectiveness of osimertinib in terms of median OS in patients with locally advanced or metastatic EGFRm NSCLC (Cohort 1).
时间窗: From start of osimertinib treatment to death, assessed up to 6 years
\- Overall survival (OS) measured as median time from start of osimertinib treatment to death. The primary measure of interest is median OS and corresponding 95% confidence interval.
To evaluate the effectiveness of osimertinib in terms of 4-year rwDFS rate in patients with stages IB-IIIA EGFRm NSCLC (Cohort 2).
时间窗: From start of osimertinib treatment to death, assessed up to 4 years.
The primary measure of interest is the 4-year real world disease-free survival rate and corresponding 95% confidence interval. \- 4-year real world disease-free survival rate for Cohort 2. (i.e., percentage of patients with clinical or radiological recurrence or death from any cause in the absence of disease recurrence 4 years after the start of osimertinib treatment, as evaluated by the treating physician according to standard clinical practice).
To evaluate the effectiveness of osimertinib in combination with pemetrexed and platinum-based chemotherapy in terms of 3-year OS in adult patients with advanced NSCLC whose tumours have EGFRm exon 19 deletions or exon 21 (L858R) substitution (Cohort 3).
时间窗: From start of osimertinib treatment to death, assessed up to 3 years.
The primary measure of interest is 3-year overall survival rate and corresponding 95% confidence interval. \- 3-year OS rate for Cohort 3 (i.e., percentage of patients alive 3 years after the start of osimertinib treatment).
To evaluate the effectiveness of osimertinib (median rwPFS) in patients with locally advanced, unresectable NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations whose disease is stable during or after platinum-based CRT (Cohort 4).
时间窗: From start of osimertinib treatment to death, assessed up to 3 years.
\- Real World Progression-free survival (rwPFS) defined as the median time from start of osimertinib treatment to clinical/radiological progression or death from any cause, in the absence of progression, as evaluated by the treating physician according to standard clinical practice. The primary measure of interest is median rwPFS and corresponding 95% confidence interval.
To evaluate the effectiveness of osimertinib in terms of median OS in patients with locally advanced or metastatic EGFRm NSCLC (Cohort 1).
时间窗: From start of osimertinib treatment to death, assessed up to 6 years
\- Overall survival (OS) measured as median time from start of osimertinib treatment to death. The primary measure of interest is median OS and corresponding 95% confidence interval.
To evaluate the effectiveness of osimertinib in terms of 4-year rwDFS rate in patients with stages IB-IIIA EGFRm NSCLC (Cohort 2).
时间窗: From start of osimertinib treatment to death, assessed up to 4 years.
The primary measure of interest is the 4-year real world disease-free survival rate and corresponding 95% confidence interval. \- 4-year real world disease-free survival rate for Cohort 2. (i.e., percentage of patients with clinical or radiological recurrence or death from any cause in the absence of disease recurrence 4 years after the start of osimertinib treatment, as evaluated by the treating physician according to standard clinical practice).
To evaluate the effectiveness of osimertinib in combination with pemetrexed and platinum-based chemotherapy in terms of 3-year OS in adult patients with advanced NSCLC whose tumours have EGFRm exon 19 deletions or exon 21 (L858R) substitution (Cohort 3).
时间窗: From start of osimertinib treatment to death, assessed up to 3 years.
The primary measure of interest is 3-year overall survival rate and corresponding 95% confidence interval. \- 3-year OS rate for Cohort 3 (i.e., percentage of patients alive 3 years after the start of osimertinib treatment).
To evaluate the effectiveness of osimertinib (median rwPFS) in patients with locally advanced, unresectable NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations whose disease is stable during or after platinum-based CRT (Cohort 4).
时间窗: From start of osimertinib treatment to death, assessed up to 3 years.
\- Real World Progression-free survival (rwPFS) defined as the median time from start of osimertinib treatment to clinical/radiological progression or death from any cause, in the absence of progression, as evaluated by the treating physician according to standard clinical practice. The primary measure of interest is median rwPFS and corresponding 95% confidence interval.
次要结局
- To further evaluate the effectiveness of osimertinib in terms of rwPFS in patients with locally advanced or metastatic EGFRm NSCLC (Cohort 1).(From start of osimertinib to clinical/radiological progression or death from any cause, whichever came first, assesed up to 6 years)
- To further evaluate the effectiveness of osimertinib in terms of rwDFS rates and OS in patients with stages IB-IIIA EGFRm NSCLC (Cohort 2).(From start of osimertinib to clinical/radiological recurrence or death from any cause, whichever came first, assesed up to 4 years)
- To further evaluate the effectiveness of osimertinib in combination with pemetrexed and platinum-based CT in terms of rwPFS and OS, in patients with advanced NSCLC whose tumours have EGFRm exon 19 deletions or exon 21 (L858R) substitution (Cohort 3).(From start of osimertinib to clinical/radiological progression or death from any cause, whichever came first, assesed up to 3 years.)
- To further evaluate the effectiveness of osimertinib in terms of CNS PFS, rwTTDM and 3-year OS (Cohort 4).(From start of osimertinib to clinical/radiological progression or death from any cause, whichever came first, assessed up to 3 years.)
- To describe the characteristics of osimertinib treatment administration for EGFRm NSCLC.(During osimertinib treatment, assessed up to 6 years in cohort 1 and up to 3 years in cohorts 2, 3 & 4.)
- To describe healthcare resource use (HCRU) during the osimertinib treatment for EGFRm NSCLC in real life.(During osimertinib treatment, assessed up to 6 years in cohort 1 and up to 3 years in cohorts 2, 3 & 4.)
- To describe the safety profile of osimertinib in a real-world setting.(During osimertinib treatment, assessed up to 6 years in cohort 1 and up to 3 years in cohorts 2, 3 & 4)
- To further evaluate the effectiveness of osimertinib in terms of rwPFS in patients with locally advanced or metastatic EGFRm NSCLC (Cohort 1).(From start of osimertinib to clinical/radiological progression or death from any cause, whichever came first, assesed up to 6 years)
- To further evaluate the effectiveness of osimertinib in terms of rwDFS rates and OS in patients with stages IB-IIIA EGFRm NSCLC (Cohort 2).(From start of osimertinib to clinical/radiological recurrence or death from any cause, whichever came first, assesed up to 4 years)
- To describe healthcare resource use (HCRU) during the osimertinib treatment for EGFRm NSCLC in real life.(During osimertinib treatment, assessed up to 6 years in cohort 1 and up to 3 years in cohorts 2, 3 & 4.)
- To further evaluate the effectiveness of osimertinib in combination with pemetrexed and platinum-based CT in terms of rwPFS and OS, in patients with advanced NSCLC whose tumours have EGFRm exon 19 deletions or exon 21 (L858R) substitution (Cohort 3).(From start of osimertinib to clinical/radiological progression or death from any cause, whichever came first, assesed up to 3 years.)
- To further evaluate the effectiveness of osimertinib in terms of CNS PFS, rwTTDM and 3-year OS (Cohort 4).(From start of osimertinib to clinical/radiological progression or death from any cause, whichever came first, assessed up to 3 years.)
- To describe the safety profile of osimertinib in a real-world setting.(During osimertinib treatment, assessed up to 6 years in cohort 1 and up to 3 years in cohorts 2, 3 & 4)
- To describe the characteristics of osimertinib treatment administration for EGFRm NSCLC.(During osimertinib treatment, assessed up to 6 years in cohort 1 and up to 3 years in cohorts 2, 3 & 4.)