Clinical trial NCT06068049: OSIREAL - Osimertinib RWE on EGFRm NSCLC in Spain
Official title: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non-small Cell Lung Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-10-05
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will include all adult EGFRm NSCLC patients receiving osimertinib according to SmPC.

Brief summary: 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 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, and 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.

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 first-line treatment with osimertinib-chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR mutated (EGFRm) advanced NSCLC.

To date, there are real-world data on osimertinib use in pretreated patients with stages IIIB-IV NSCLC EGFRm/T790M in Spain, obtained from the OSIREX study. However, there are no real-world data on osimertinib either in first-line 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 (RWD) aims to provide data on osimertinib use as adjuvant treatment in adult patients diagnosed with stages IB-IIIA EGFRm NSCLC, in first line treatment in patients with locally advanced or metastatic EGFRm NSCLC, 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.

Detailed description: 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.

The standard of care for patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-sensitizing mutations is treatment with a first-generation or second-generation EGFR-TKI such as gefitinib, erlotinib, or afatinib. Treatment with EGFR-TKIs in this patient population has extended progression-free survival relative to chemotherapy as initial therapy.

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)) 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. The FLAURA trial showed that treatment with osimertinib significantly prolongs progression-free survival (PFS) compared to EGFR TKI comparator (median 18.9 months and 10.2 months, respectively, HR=0.46, 95% CI: 0.37, 0.57; P\<0.0001) (5) and improves overall survival (OS) (HR=0.799 \[95.05% CI: 0.641, 0.997\]) compared to standard EGFR tyrosine kinase inhibitors (TKIs), in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). A greater proportion of patients treated with osimertinib were alive at 12, 18, 24 and 36 months (89%, 81%, 74% and 54% respectively) compared to patients treated with EGFR TKI comparator (83%, 71%, 59% and 44% respectively).

The results of the ADAURA trial showed that adjuvant treatment with osimertinib reduced the risk of recurrence or death by 83% in stages II to IIIA, and in 80% in stages IB-IIIA, compared with placebo, in patients with NSCLC with completely resected stage IB to IIIA disease and confirmed EGFR mutation. Additionally, osimertinib demonstrated a highly statistically significant improvement in disease free survival (DFS) and HRQoL was maintained. A DFS benefit favouring osimertinib over placebo was seen across all prespecified subgroups, including those based on disease stage, EGFR sensitizing mutation, ethnicity and receipt of adjuvant chemotherapy. Furthermore, the DFS benefit with osimertinib was similar in patients who had or had not received chemotherapy.

The FLAURA2 trial showed that first-line treatment with osimertinib-chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR mutated advanced NSCLC . Investigator-assessed progression-free survival was significantly longer in the osimertinib-chemotherapy group than in the osimertinib group (hazard ratio for disease progression or death, 0.62; 95% confidence interval \[CI\], 0.49 to 0.79; P\<0.001). At 24 months, 57% (95% CI, 50 to 63) of the patients in the osimertinib- chemotherapy group and 41% (95% CI, 35 to 47) of those in the osimertinib group were alive and progression-free. An objective response was observed in 83% of the patients in the osimertinib-chemotherapy group and in 76% of those in the osimertinib group; the median response duration was 24.0 months (95% CI, 20.9 to 27.8) and 15.3 months (95% CI, 12.7 to 19.4), respectively. The safety profile of osimertinib plus pemetrexed and a platinum-based agent was consistent with the established profiles of the individual agents.

Eligibility criteria: Inclusion Criteria:

* 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 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).
* 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.

Exclusion Criteria:

* Osimertinib treatment administration in a clinical trial setting.

Primary outcomes:
measure: To evaluate the effectiveness of osimertinib in terms of median OS in patients with locally advanced or metastatic EGFRm NSCLC (Cohort 1).
timeFrame: From start of osimertinib treatment to death, assesed up to 6 years
measure: To evaluate the effectiveness of osimertinib in terms of 4-year rwDFS rate in patients with stages IB-IIIA EGFRm NSCLC (Cohort 2).
timeFrame: From start of osimertinib treatment to death, assesed up to 4 years.
measure: 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).
timeFrame: From start of osimertinib treatment to death, assesed up to 3 years.
Secondary outcomes:
measure: To further evaluate the effectiveness of osimertinib in terms of rwPFS in patients with locally advanced or metastatic EGFRm NSCLC (Cohort 1).
timeFrame: From start of osimertinib to clinical/radiological progression or death from any cause, whichever came first, assesed up to 6 years
measure: To further evaluate the effectiveness of osimertinib in terms of rwDFS rates and OS in patients with stages IB-IIIA EGFRm NSCLC (Cohort 2).
timeFrame: From start of osimertinib to clinical/radiological recurrence or death from any cause, whichever came first, assesed up to 4 years
measure: 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).
timeFrame: From start of osimertinib to clinical/radiological progression or death from any cause, whichever came first, assesed up to 3 years.
measure: To describe the characteristics of osimertinib treatment administration for EGFRm NSCLC.
timeFrame: During osimertinib treatment, assesed up to 6 years in cohort 1 and up to 3 years in cohorts 2 & 3.
measure: To describe healthcare resource use (HCRU) during the osimertinib treatment for EGFRm NSCLC in real life.
timeFrame: During osimertinib treatment, assesed up to 6 years in cohort 1 and up to 3 years in cohorts 2 & 3.
measure: To describe the safety profile of osimertinib in a real-world setting.
timeFrame: During osimertinib treatment, assesed up to 6 years in cohort 1 and up to 3 years in cohorts 2 % 3
Other outcomes:
measure: To describe the effectiveness, safety and use of healthcare resources of osimertinib monotherapy in patients with locally advanced or metastatic EGFRm NSCLC (Cohort 1) who have uncommon EGFR mutations.
timeFrame: OS from start of osimertinib treatment to death and rates at months 6, 12, 18, and 2, 3, 4, 5 years after starting osimertinib.
measure: To describe the effectiveness, safety and use of healthcare resources of osimertinib monotherapy in elderly patients (>65 and >75 years) with locally advanced or metastatic EGFRm NSCLC (Cohorts 1 & 3).
timeFrame: From start of osimertinib treatment to death and rates at months 6, 12 and 18, and 2, 3, 4 and 5 (only cohort 1) years after starting osimertinib.
measure: To evaluate patient reported outcomes and experience measures (PROMs and PREMs) in EGFRm NSCLC patients treated with Osimertinib as adjuvant treatment (only applicable to cohort 2).
timeFrame: SATMED-Q, SF-36: at study inclusion and every 6 months. ADAQ: at study inclusion and every week during on osimertinib treatment, an average of 3 years.
measure: To evaluate PROMs and PREMs in patients with advanced NSCLC treated with osimertinib in combination with pemetrexed and platinum-based chemotherapy, whose tumours have EGFRm exon 19 deletions or exon 21 (L858R) substitution (Cohort 3).
timeFrame: SATMED-Q, SF-36: at study inclusion and every 6 months during osimertinib treatment, an average of 3 years. ADAQ: at study inclusion and every week during osimertinib treatment, an average of 3 years.
measure: To describe the adherence of patients with EGFRm NSCLC treated with osimertinib under real-world conditions (Cohorts 2 & 3)..
timeFrame: ADAQ: reported at study inclusion and weekly thereafter during prospective follow-iup on osimertinib treatment, an average of 3 years.
measure: To assess factors associated with outcomes (OS, rwDFS, rwPFS, rwTTD, rwTFST) among patients treated with osimertinib 1L (cohorts 1 & 3), and patients treated with osimertinib in the adjuvant setting (cohort 2).
timeFrame: rwTTD from treatment initiation to time to discontinuation; rwTFST from treatment initiation till the start of subsequent therapy/death. OS rates at months 6, 12 and 18, and 2, 3, (cohort 3), 4 and 5 years (cohorts 1 & 2) years after starting osimertinib
measure: To describe the therapies received before and after osimertinib treatment progression or relapse.
timeFrame: Before and after osimertinib treatment, assesed up to 6 years in cohort 1 and up to 3 years in cohorts 2 and 3.
Locations:
city: Alicante
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: C Rdoba
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: Gran Canaria
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: Ja N
country: Spain
facility: Research Site
city: L Rida
country: Spain
facility: Research Site
city: La Coru A
country: Spain
facility: Research Site
city: Le N
country: Spain
facility: Research Site
city: M Laga
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Murcia
country: Spain
facility: Research Site
city: Ourense
country: Spain
facility: Research Site
city: Palma
country: Spain
facility: Research Site
city: Sabadell
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Tenerife
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valladolid
country: Spain
facility: Research Site
city: Vigo
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
Study officials:
References: